Trial Outcomes & Findings for A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064) (NCT NCT01605396)

NCT ID: NCT01605396

Last Updated: 2019-03-25

Results Overview

PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 80 participants
• Primary outcome timeframe: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
• Results posted on: 2019-03-25

Participant Flow

Of 196 screened participants, 80 were randomized to either ridaforolimus plus dalotuzumab plus exemestane or ridaforolimus plus exemestane.

Participant milestones

Measure	Ridaforolimus + Dalotuzumab + Exemestane Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Overall Study STARTED	40	40
Overall Study Treated	39	40
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	40	40

Reasons for withdrawal

Measure	Ridaforolimus + Dalotuzumab + Exemestane Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Overall Study Adverse Event	5	3
Overall Study Lost to Follow-up	1	0
Overall Study Non-Compliance With Study Drug	1	1
Overall Study Physician Decision	2	2
Overall Study Progressive Disease	23	27
Overall Study Withdrawal by Subject	4	2
Overall Study Transfer Off Study	4	5

Baseline Characteristics

A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)

Baseline characteristics by cohort

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=40 Participants Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 Participants Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.	Total n=80 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 9.0 • n=5 Participants	57.7 Years STANDARD_DEVIATION 11.8 • n=7 Participants	59.2 Years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	40 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	34 Participants n=7 Participants	69 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 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
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Population: All randomized participants.

PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

Outcome measures

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=40 Participants Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 Participants Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)	23.29 Weeks Interval 8.71 to 38.43	31.86 Weeks Interval 16.0 to 39.29

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All randomized participants with available Week 16 target lesion measurements.

The percent change from baseline to Week 16 in the sum of target lesion diameters as determined by anatomic imaging was defined as the line length (i.e., diameter) for each target lesion identified at baseline summed across all lesions at baseline, and separately at each post-baseline time point. The primary analysis was conducted using a constrained longitudinal data analysis (cLDA) method and target lesion measurements according to the BICR. Percent change from baseline in sum of target lesion diameters at Week 16 was reported for each treatment arm.

Outcome measures

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=15 Participants Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=32 Participants Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16	-19.3 percent change Standard Deviation 20.4	-10.7 percent change Standard Deviation 28.5

SECONDARY outcome

Timeframe: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Population: All randomized participants.

ORR was defined as the percentage of participants whose best response was complete response (CR; disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or partial response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.

Outcome measures

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=40 Participants Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 Participants Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).	15.0 Percentage of Participants Interval 5.7 to 29.8	25.0 Percentage of Participants Interval 12.7 to 41.2

SECONDARY outcome

Timeframe: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Population: All randomized participants.

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date last known to be alive. OS was analyzed using the Kaplan-Meier method and median OS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, all participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

Outcome measures

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=40 Participants Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 Participants Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Overall Survival (OS)	NA Weeks Median OS could not be calculated due to an insufficient number of deaths on study (i.e. median OS was not reached).	NA Weeks Interval 60.6 to Median OS could not be calculated due to an insufficient number of deaths on study (i.e. median OS was not reached).

Adverse Events

Ridaforolimus + Dalotuzumab + Exemestane

Serious events: 8 serious events

Other events: 39 other events

Deaths: 1 deaths

Ridaforolimus + Exemestane

Serious events: 17 serious events

Other events: 40 other events

Deaths: 2 deaths

Serious adverse events

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=39 participants at risk Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 participants at risk Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Cardiac disorders Myocardial infarction	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Cardiac disorders Sinus tachycardia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Diarrhoea	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Haematochezia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Vomiting	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Asthenia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Disease progression	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Appendicitis	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Escherichia sepsis	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Gastroenteritis	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Ophthalmic herpes zoster	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Pneumonia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Upper respiratory tract infection	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Urinary tract infection	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Injury, poisoning and procedural complications Oesophagitis chemical	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Chondrocalcinosis	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Cognitive disorder	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Psychiatric disorders Mood altered	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.

Other adverse events

Measure	Ridaforolimus + Dalotuzumab + Exemestane n=39 participants at risk Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.	Ridaforolimus + Exemestane n=40 participants at risk Participants received ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	15.4% 6/39 • Number of events 8 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	22.5% 9/40 • Number of events 11 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Blood and lymphatic system disorders Leukopenia	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Blood and lymphatic system disorders Neutropenia	7.7% 3/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Abdominal pain	15.4% 6/39 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Abdominal pain upper	10.3% 4/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Constipation	17.9% 7/39 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	20.0% 8/40 • Number of events 11 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Diarrhoea	35.9% 14/39 • Number of events 31 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	37.5% 15/40 • Number of events 28 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Dry mouth	7.7% 3/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Dyspepsia	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Nausea	23.1% 9/39 • Number of events 18 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	22.5% 9/40 • Number of events 11 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Oral pain	7.7% 3/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Stomatitis	76.9% 30/39 • Number of events 54 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	90.0% 36/40 • Number of events 88 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Toothache	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Gastrointestinal disorders Vomiting	20.5% 8/39 • Number of events 20 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	20.0% 8/40 • Number of events 8 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Asthenia	25.6% 10/39 • Number of events 13 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	35.0% 14/40 • Number of events 15 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Chest pain	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Chills	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Fatigue	28.2% 11/39 • Number of events 13 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	17.5% 7/40 • Number of events 9 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Local swelling	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Oedema peripheral	7.7% 3/39 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	25.0% 10/40 • Number of events 12 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
General disorders Pyrexia	10.3% 4/39 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	12.5% 5/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Cellulitis	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Cystitis	10.3% 4/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Gingivitis	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Herpes zoster	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Nasopharyngitis	7.7% 3/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Infections and infestations Upper respiratory tract infection	2.6% 1/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Alanine aminotransferase increased	7.7% 3/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Aspartate aminotransferase increased	15.4% 6/39 • Number of events 9 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Blood cholesterol increased	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Neutrophil count decreased	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Platelet count decreased	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	12.5% 5/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations Weight decreased	7.7% 3/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Investigations White blood cell count decreased	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Decreased appetite	38.5% 15/39 • Number of events 16 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	27.5% 11/40 • Number of events 13 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Hyperglycaemia	28.2% 11/39 • Number of events 14 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	25.0% 10/40 • Number of events 20 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Arthralgia	12.8% 5/39 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	12.5% 5/40 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Back pain	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Bone pain	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Joint swelling	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Muscle spasms	17.9% 7/39 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Myalgia	10.3% 4/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 8 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Dizziness	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Dysgeusia	35.9% 14/39 • Number of events 16 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	15.0% 6/40 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Headache	15.4% 6/39 • Number of events 6 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	32.5% 13/40 • Number of events 18 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Neuropathy peripheral	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Nervous system disorders Tremor	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	2.5% 1/40 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Psychiatric disorders Anxiety	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Psychiatric disorders Insomnia	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Renal and urinary disorders Renal failure	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Reproductive system and breast disorders Breast pain	5.1% 2/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Cough	20.5% 8/39 • Number of events 10 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	25.0% 10/40 • Number of events 13 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.3% 4/39 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	20.0% 8/40 • Number of events 10 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Epistaxis	25.6% 10/39 • Number of events 15 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Dermatitis	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	0.00% 0/40 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Dermatitis acneiform	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Dry skin	7.7% 3/39 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Erythema	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/39 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Onycholysis	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	5.0% 2/40 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	12.5% 5/40 • Number of events 7 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Rash	20.5% 8/39 • Number of events 12 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	20.0% 8/40 • Number of events 13 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Skin and subcutaneous tissue disorders Skin lesion	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	7.5% 3/40 • Number of events 3 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Vascular disorders Hypertension	5.1% 2/39 • Number of events 2 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 5 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.
Vascular disorders Lymphoedema	2.6% 1/39 • Number of events 1 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.	10.0% 4/40 • Number of events 4 • From Day 1 through Post Treatment visit at 4 weeks after last dose of treatment (up to ~17 months) All randomized participants who received at least one dose of study treatment. For nine participants who continued to receive treatment under compassionate use after database lock, safety data was not included in any study database but was reported to global safety.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
• Publication restrictions are in place

Restriction type: OTHER