Trial Outcomes & Findings for An Open-Label, Phase Ib/II Clinical Trial Of Cdk 4/6 Inhibitor, Ribociclib (Lee011), In Combination With Trastuzumab Or T-Dm1 For Advanced/Metastatic Her2-Positive Breast Cancer. (NCT NCT02657343)

Last Updated: 2022-08-01

Results Overview

Standard 3+3 phase-I design will be utilized in this trial. Briefly, a minimum of 3 evaluable patients will be entered at first dose level (=300 mg ribociclib) and T-DM1 (3.6 mg/kg IV). If 1 out of the first 3 patients enrolled experiences a dose-limiting toxicity (DLT), 3 additional patients will be enrolled to that dose level. If no more than 1 patient in 6 experiences a DLT, dose escalation of ribociclib will continue to next dose-level. If 2 or more patients at any given dose level experience a DLT, dose escalation will stop and the Recommended Phase2 Dose (RP2D) will be defined. Maximum dose-escalation of Ribociclib (LEE011) will be up to 600 mg.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Disease was evaluated at baseline and each cycle on treatment and the end of treatment. Toxicity was evaluated each cycle on treatment, end of treatment and 30 days follow-up. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Results posted on

2022-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 400 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose: 500 mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 500 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose: 600mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 600 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study] * Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.
Overall Study STARTED	3	3	3	3	13
Overall Study COMPLETED	2	1	3	3	12
Overall Study NOT COMPLETED	1	2	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg] * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 400 mg (n = 3) Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study] * Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.
Overall Study Death	0	2	0
Overall Study Patient went to hospice	1	0	0
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

An Open-Label, Phase Ib/II Clinical Trial Of Cdk 4/6 Inhibitor, Ribociclib (Lee011), In Combination With Trastuzumab Or T-Dm1 For Advanced/Metastatic Her2-Positive Breast Cancer.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg] n=3 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg] n=3 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 400 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 3: 500mg] n=3 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 500 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 4: 600mg] n=3 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 600 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study] n=12 Participants * Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.	Cohort C: Ribociclib + Trastuzumab + Fulvestrant [Phase 1b/2 Study] * Ribociclib will be given orally once a day continuously for a 28-day cycle of treatment (except at Dose Level -1, when Ribociclib is given Days 1-21 of a 28 day cycle). * Trastuzumab will be given as IV infusions over a pre-determined period of time and dose. Fulvestrant will be dosed approximately every 28 days as per standard of care.	Total n=24 Participants Total of all reporting groups
Age, Continuous	52 years n=5 Participants	55 years n=7 Participants	52 years n=5 Participants	47 years n=4 Participants	51 years n=21 Participants	—	52 years n=115 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants	—	24 Participants n=115 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	—	0 Participants n=115 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	12 Participants n=21 Participants	—	19 Participants n=115 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	—	5 Participants n=115 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	12 participants n=21 Participants	—	24 participants n=115 Participants

PRIMARY outcome

Timeframe: Disease was evaluated at baseline and each cycle on treatment and the end of treatment. Toxicity was evaluated each cycle on treatment, end of treatment and 30 days follow-up. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort A: Recommended Phase2 Dose (RP2D)	400 mg

PRIMARY outcome

Timeframe: at week 12

CBR is defined as the proportion of patients with a complete response (CR) or partial response (PR), or with stable disease (SD) at week 24 by RECIST 1.1 criteria. CBR will be reported with 90% confidence interval, adjusting for two-stage design using the method from Atkinson and Brown.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Clinical Benefit Rate (CBR) CR	0 Participants
Cohort B: Clinical Benefit Rate (CBR) PR	0 Participants
Cohort B: Clinical Benefit Rate (CBR) SD	3 Participants
Cohort B: Clinical Benefit Rate (CBR) Progressive disease	9 Participants

PRIMARY outcome

Timeframe: at week 12

Population: no patients enrolled

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. median follow-up is 12.4 months

All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity neutropenia	4 number of incidences
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity leukopenia	4 number of incidences
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity thrombocytopenia	2 number of incidences
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity febrile neutropenia	1 number of incidences
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity anemia	3 number of incidences
Cohort A: Incidence of Grade 3 Treatment-Related Toxicity lymphopenia	2 number of incidences

SECONDARY outcome

Timeframe: PK blood collection is scheduled at 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24 hours following dosing of ribociclib.

Population: 0 patient data collected because study plan changed

pharmacokinetics (PK) tudies demonstrated dose-related inhibition of Rb phosphorylation in tumors, with continuous dosing over at least 3-5 days being required to achieve optimal target inhibition.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Objective response rate(ORR) was defined as the portion of patients with complete response or partial response by RECIST 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort A: Objective Response Rate (ORR)	16.7 percentage of participants Interval 3.0 to 44.0

SECONDARY outcome

Timeframe: Disease was evaluated radiologically every cycles on treatment and in long-term follow-up every 12 weeks. Median follow-up in this study cohort was 12.4 months.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort A: Median Progression-Free Survival (PFS)	10.4 Months Interval 2.7 to 19.3

SECONDARY outcome

Timeframe: taken at any time in Cycle 2 Day 10-18.

Population: biopsy data not collected because study plan changed

Optional tumor samples (if safely accessible and feasible) will be taken pre- and post-treatment in order to assess dose-dependent target modulation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Objective Response Rate (ORR)	0 rate

SECONDARY outcome

Timeframe: Disease was evaluated radiologically every cycles on treatment and in long-term follow-up every 12 weeks. Median follow-up in this study cohort was 5 months.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Median Progression-Free Survival (PFS)	1.33 Months Interval 0.92 to 2.57

SECONDARY outcome

Timeframe: Participants were followed long-term for survival every 12 weeks from the end of treatment until death or lost to follow-up. Median follow-up in this study cohort was 5 months.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Overall Survival (OS)	7.9 Months Interval 3.4 to based on Kaplan-Meier method limitation, the upper interval cannot be reached

SECONDARY outcome

Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. median follow-up is 12.4 months

Outcome measures

Outcome measures
Measure	Cohort A: Ribociclib + T-DM1 n=12 Participants * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Incidence of Grade 3 Treatment-Related Toxicity neutropenia	2 number of incidences
Cohort B: Incidence of Grade 3 Treatment-Related Toxicity fatigue	1 number of incidences
Cohort B: Incidence of Grade 3 Treatment-Related Toxicity pain	1 number of incidences

SECONDARY outcome

Timeframe: taken at any time in Cycle 2 Day 10-18.

Population: biopsy will not be done because the study plan changed

Optional tumor samples (if safely accessible and feasible) will be taken pre- and post-treatment in order to assess dose-dependent target modulation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration is 0 days since cohort C never enrolled.

Population: data not collected because no patient enrolled

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Disease was evaluated radiologically every cycles on treatment and in long-term follow-up every 12 weeks. Reality follow-up is 0 days since cohort C never enrolled.

Population: data not collected because no patients enrolled

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants were followed long-term for survival every 12 weeks from the end of treatment until death or lost to follow-up. 0 days in reality since cohort C never enrolled.

Population: data not collected because no patients enrolled

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. 0 days in reality since cohort C never enrolled.

Population: data not collected because no patients enrolled

all grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: taken at any time in Cycle 2 Day 10-18.

Population: no patients enrolled

Optional tumor samples (if safely accessible and feasible) will be taken pre- and post-treatment in order to assess dose-dependent target modulation.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg]

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg]

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Cohort A: Ribociclib + T-DM1 [Dose 3: 500mg]

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort A: Ribociclib + T-DM1 [Dose 4: 600mg]

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study]

Serious events: 10 serious events

Other events: 12 other events

Deaths: 0 deaths

Cohort C: Ribociclib + Trastuzumab + Fulvestrant [Phase 1b/2 Study]

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 400 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 3: 500mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 500 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 4: 600mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 600 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study] n=12 participants at risk * Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.	Cohort C: Ribociclib + Trastuzumab + Fulvestrant [Phase 1b/2 Study] * Ribociclib will be given orally once a day continuously for a 28-day cycle of treatment (except at Dose Level -1, when Ribociclib is given Days 1-21 of a 28 day cycle). * Trastuzumab will be given as IV infusions over a pre-determined period of time and dose. Fulvestrant will be dosed approximately every 28 days as per standard of care.
Investigations Alanine aminotransferase increased	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	25.0% 3/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	16.7% 2/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	41.7% 5/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	16.7% 2/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Urinary tract infection	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 4/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Other adverse events

Other adverse events
Measure	Cohort A: Ribociclib + T-DM1 [Dose 1: 300mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 300 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 2: 400mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 400 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 3: 500mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 500 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort A: Ribociclib + T-DM1 [Dose 4: 600mg] n=3 participants at risk * Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of 600 mg (n = 3) Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.	Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study] n=12 participants at risk * Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.	Cohort C: Ribociclib + Trastuzumab + Fulvestrant [Phase 1b/2 Study] * Ribociclib will be given orally once a day continuously for a 28-day cycle of treatment (except at Dose Level -1, when Ribociclib is given Days 1-21 of a 28 day cycle). * Trastuzumab will be given as IV infusions over a pre-determined period of time and dose. Fulvestrant will be dosed approximately every 28 days as per standard of care.
Investigations Activated partial thromboplastin time prolonged	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	83.3% 10/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Blurred vision	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Breast pain	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Injury, poisoning and procedural complications Bruising	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Chills	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Conjunctivitis	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	16.7% 2/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Cystitis noninfective	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	41.7% 5/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Dry eye	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	16.7% 2/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dry mouth	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	16.7% 2/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Duodenal hemorrhage	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Edema face	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Electrocardiogram QT corrected interval prolonged	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Epistaxis	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophageal pain	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fever	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Flu like symptoms	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infections and infestations - Other, specify	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Insomnia	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Investigations - Other, specify	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Lung infection	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	25.0% 3/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	41.7% 5/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Neck pain	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Oral hemorrhage	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Pain	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pain of skin	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Pericardial effusion	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral motor neuropathy	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Scalp pain	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Sinusitis	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Skin infection	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Stomach pain	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Tremor	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Urinary tract infection	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Watering eyes	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	8.3% 1/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Weight gain	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	0.00% 0/12 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.	— 0/0 • AE data collected every cycle from the time of the first dose of study treatment, through the study of treatment until 30 days after removal from study or death, whichever occurs first. Cohort A AEs were observed up to 24 weeks, Cohort B AEs were observed up tp 1 cycle (3 weeks). Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Additional Information

Sara Tolaney, MD, MPH

Dana-Farber Cancer Institute

Phone: (877) 442-3324

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place