Trial Outcomes & Findings for A Study of LY2835219 in Japanese Participants With Advanced Cancer (NCT NCT02014129)

NCT ID: NCT02014129

Last Updated: 2020-08-24

Results Overview

DLT is defined as an adverse event between Day -3 and Day 29 of Cycle 1 that is possibly related to the study drug and fulfills any one of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Cycle 1 = 32 days

Results posted on

2020-08-24

Participant Flow

Participants completed the trial if they received at least one dose of study drug and met discontinuation criteria.

Participant milestones

Participant milestones
Measure	Cohort 1 - 100 mg Abemaciclib 100 milligram (mg) abemaciclib administered orally every 12 hours (Q12H) in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Overall Study STARTED	3	3	6
Overall Study Received at Least One Dose of Study Drug	3	3	6
Overall Study COMPLETED	3	3	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of LY2835219 in Japanese Participants With Advanced Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 - 100 mg Abemaciclib n=3 Participants 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 Participants 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 Participants 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Total n=12 Participants Total of all reporting groups
Age, Continuous	61.3 years STANDARD_DEVIATION 11.06 • n=5 Participants	63.0 years STANDARD_DEVIATION 1.00 • n=7 Participants	56.0 years STANDARD_DEVIATION 11.70 • n=5 Participants	59.1 years STANDARD_DEVIATION 9.77 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Japan	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 = 32 days

Population: All participants who received at least one dose of study drug and took at least 75% of planned dose in Cycle 1 or experienced a DLT in Cycle 1.

Outcome measures

Outcome measures
Measure	Cohort 1 - 100 mg Abemaciclib n=3 Participants 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 Participants 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 Participants 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT)	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hours (hr) postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)

Population: All participants who received at least one dose of study drug and had evaluable data for Cmax.

Maximum plasma concentration on Day -3 and Day 28 of Cycle 1.

Outcome measures

Outcome measures
Measure	Cohort 1 - 100 mg Abemaciclib n=3 Participants 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 Participants 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 Participants 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib Cycle 1 Day -3	127 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 51	167 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 40	214 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 87
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib Cycle 1 Day 28	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, no geometric mean or Coefficient of variation (CV), individual values reported: 231.58, 1379.20.	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, no geometric mean or CV, individual values reported:1381.46, 148.86.	298 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 64

SECONDARY outcome

Timeframe: Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hr postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)

Population: All participants who received at least one dose of study drug and had evaluable data for AUC.

AUC on Day -3 and Day 28 of Cycle 1 are AUC from time zero to infinity \[AUC(0-∞)\] and AUC during one dosing interval at steady state (AUCτ,ss), respectively.

Outcome measures

Outcome measures
Measure	Cohort 1 - 100 mg Abemaciclib n=3 Participants 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 Participants 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 Participants 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib AUC(0-∞)	NA Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation NA N=2, no geometric mean or CV, individual values reported: 6970, 6450.	4450 Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation 39	5480 Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation 95
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib AUCτ,ss (n=2,2,5)	NA Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation NA N=2, no geometric mean or CV, individual values reported: 2070, 14100.	NA Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation NA N=2, no geometric mean or CV, individual values reported: 15500, 1460.	3020 Nanogramhour/Millilitre (nghr/mL) Geometric Coefficient of Variation 73

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease (Up To 24 months)

Population: All participants who received at least one dose of study drug.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1 - 100 mg Abemaciclib n=3 Participants 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 Participants 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 Participants 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Percentage of Participants With a Tumor Response: Objective Response Rate (ORR)	0 percentage of participants	0 percentage of participants	0 percentage of participants

Adverse Events

Cohort 1 - 100 mg Abemaciclib

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 2 - 150 mg Abemaciclib

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 3 - 200 mg Abemaciclib

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 - 100 mg Abemaciclib n=3 participants at risk 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 participants at risk 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 participants at risk 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Gastrointestinal disorders Gastric fistula	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Infections and infestations Biliary tract infection	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Infections and infestations Lung infection	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Cohort 1 - 100 mg Abemaciclib n=3 participants at risk 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 2 - 150 mg Abemaciclib n=3 participants at risk 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Cohort 3 - 200 mg Abemaciclib n=6 participants at risk 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 12 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 12 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Eye disorders Lacrimation increased	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Eye disorders Vitreous floaters	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Anal inflammation	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 3 All participants who received at least one dose of study drug.	100.0% 6/6 • Number of events 8 All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	50.0% 3/6 • Number of events 5 All participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 All participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	66.7% 4/6 • Number of events 6 All participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
General disorders Fatigue	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
General disorders Malaise	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 All participants who received at least one dose of study drug.
General disorders Mucosal inflammation	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 2 All participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Performance status decreased	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Pyrexia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 All participants who received at least one dose of study drug.
Immune system disorders Seasonal allergy	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Biliary tract infection	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Infections and infestations Cystitis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Hordeolum	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 All participants who received at least one dose of study drug.
Infections and infestations Paronychia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Rhinitis	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Infections and infestations Skin infection	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 2 All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/3 All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	83.3% 5/6 • Number of events 6 All participants who received at least one dose of study drug.
Investigations Electrocardiogram qt prolonged	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Investigations Haemoglobin decreased	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Investigations Lymphocyte count decreased	33.3% 1/3 • Number of events 2 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 All participants who received at least one dose of study drug.
Investigations Platelet count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 4 All participants who received at least one dose of study drug.
Investigations Weight decreased	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Investigations White blood cell count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	66.7% 4/6 • Number of events 6 All participants who received at least one dose of study drug.
Investigations White blood cell count increased	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	50.0% 3/6 • Number of events 3 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	50.0% 3/6 • Number of events 3 All participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 4 All participants who received at least one dose of study drug.
Nervous system disorders Somnolence	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Renal and urinary disorders Cystitis noninfective	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 All participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.