Trial Outcomes & Findings for Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In (NCT NCT02708680)

NCT ID: NCT02708680

Last Updated: 2024-12-04

Results Overview

Phase 1b employed a classical 3+3 design, with the determination of DLT based on entinostat in combination with atezolizumab within the first cycle of treatment (that is, between Day 1 to Day 21 of Cycle 1). Six participants were required to be treated in a dose level for it to be considered MTD or the Recommended Phase 2 Dose (RP2D). A DLT was defined as the occurrence of specific events, defined in the protocol, that were considered by the investigator to be at least possibly related to study drug using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03.The DLT assessment window (Cycle 1) was the time period between Cycle 1 Day 1 until Cycle 2 Day 1 (expected to be 21 days after Cycle 1 Day 1).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 89 participants
• Primary outcome timeframe: Up to 21 days after Cycle 1 Day 1
• Results posted on: 2024-12-04

Participant Flow

Participant milestones

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab. Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion Phase: Entinostat Plus Atezolizumab Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion Phase: Placebo Plus Atezolizumab Participants received placebo in combination with atezolizumab 1200 mg.
Overall Study STARTED	8	40	41
Overall Study Received At Least 1 Dose Of Study Drug	8	40	39
Overall Study Dose-limiting Toxicity (DLT) Evaluable	6	0	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	40	41

Reasons for withdrawal

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab. Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion Phase: Entinostat Plus Atezolizumab Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion Phase: Placebo Plus Atezolizumab Participants received placebo in combination with atezolizumab 1200 mg.
Overall Study Withdrawal by Subject	4	12	12
Overall Study Death	4	19	21
Overall Study Lost to Follow-up	0	3	3
Overall Study Study Terminated By Sponsor	0	5	4
Overall Study Other than Specified	0	0	1
Overall Study Discontinued Treatment but Remained in Follow-up	0	1	0

Baseline Characteristics

Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In

Baseline characteristics by cohort

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=8 Participants Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.	Total n=89 Participants Total of all reporting groups
Age, Continuous	57.5 years n=5 Participants	56.9 years n=7 Participants	54.3 years n=5 Participants	56.2 years n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	89 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	35 Participants n=7 Participants	30 Participants n=5 Participants	71 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	6 Participants n=5 Participants	30 Participants n=7 Participants	30 Participants n=5 Participants	66 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black Or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 21 days after Cycle 1 Day 1

Population: A participant that experienced an adverse event (AE) meeting DLT criteria during Cycle 1 or who received the full dose of atezolizumab and all doses of entinostat during Cycle 1 without experiencing a DLT was considered DLT evaluable.

Phase 1b employed a classical 3+3 design, with the determination of DLT based on entinostat in combination with atezolizumab within the first cycle of treatment (that is, between Day 1 to Day 21 of Cycle 1). Six participants were required to be treated in a dose level for it to be considered MTD or the Recommended Phase 2 Dose (RP2D). A DLT was defined as the occurrence of specific events, defined in the protocol, that were considered by the investigator to be at least possibly related to study drug using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03.The DLT assessment window (Cycle 1) was the time period between Cycle 1 Day 1 until Cycle 2 Day 1 (expected to be 21 days after Cycle 1 Day 1).

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=6 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab Participants received placebo in combination with atezolizumab 1200 mg.
Phase 1b: Participants Experiencing DLT	0 Participants	—

PRIMARY outcome

Timeframe: Up to 21 days after Cycle 1 Day 1

Population: Participants evaluable for DLTs. A participant that experienced an AE meeting DLT criteria during Cycle 1 or who received the full dose of atezolizumab and all doses of entinostat during Cycle 1 without experiencing a DLT was considered DLT evaluable.

Phase 1b employed a classical 3+3 design, with the determination of the RP2D based on entinostat in combination with atezolizumab within the first cycle of treatment (that is, between Day 1 to Day 21 of Cycle 1). The RP2D was defined as equal to or less than the preliminary maximum tolerated dose (MTD) and was determined in discussion with the sponsor, the study medical monitor, and dose determination phase investigators. The MTD was defined as the highest dose level at which <33% of 6 participants experience DLT.

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=6 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab Participants received placebo in combination with atezolizumab 1200 mg.
Phase 1b: Determination of the RP2D	5 milligram	—

PRIMARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (FAS): all participants who were randomized to study treatment, regardless of whether they actually received study medication.

The duration of PFS, assessed using RECIST 1.1, was used to evaluate the efficacy of entinostat at the RP2D in combination with atezolizumab in participants with advanced triple negative breast cancer (aTNBC). It was defined as the number of months from randomization to the earlier of progressive disease or death due to any cause. One month was considered 30.4375 days. PFS (months) = (Date of Progression or Censoring - Date of Randomization + 1)/30.4375.

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.
Phase 2 Expansion: Duration of Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	1.68 months Interval 1.41 to 3.09	1.51 months Interval 1.41 to 2.43

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (FAS): all participants who were randomized to study treatment, regardless of whether they actually received study medication.

The duration of PFS, assessed using irRECIST, was used to evaluate the efficacy of entinostat at the RP2D in combination with atezolizumab in participants with aTNBC. It was defined as the number of months from randomization to the earlier of progressive disease or death due to any cause. One month was considered 30.4375 days. PFS (months) = (Date of Progression or Censoring - Date of Randomization + 1)/30.4375.

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.
Phase 2 Expansion: Duration of PFS Using Immune Response RECIST (irRECIST)	1.68 months Interval 1.45 to 3.81	1.54 months Interval 1.41 to 2.83

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (FAS): all participants who were randomized to study treatment, regardless of whether they actually received study medication.

ORR was defined as the crude percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) assessed using RECIST 1.1 and irRECIST. ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants. The overall response was determined locally by the investigator at each scheduled assessment.

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.
Phase 2 Expansion: Overall Response Rate (ORR) Using RECIST 1.1 and irRECIST ORR per RECIST 1.1	12.5 percentage of participants	2.4 percentage of participants
Phase 2 Expansion: Overall Response Rate (ORR) Using RECIST 1.1 and irRECIST ORR per irRECIST 1.1	12.5 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (FAS): all participants who were randomized to study treatment, regardless of whether they actually received study medication.

CBR was estimated based on the crude percentage of participants in each treatment arm whose best overall response during the course of study treatment was CR, PR, or stable disease (SD) lasting for at least 24 weeks (measured from the date of randomization to the last date where SD was reported).

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.
Phase 2 Expansion: Clinical Benefit Rate (CBR) Using RECIST 1.1 and irRECIST CBR per RECIST 1.1	15.0 percentage of participants	7.3 percentage of participants
Phase 2 Expansion: Clinical Benefit Rate (CBR) Using RECIST 1.1 and irRECIST CBR per irRECIST 1.1	15.0 percentage of participants	7.3 percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Full Analysis Set (FAS): all participants who were randomized to study treatment, regardless of whether they actually received study medication.

OS was defined as the number of months from randomization to date of death from any cause. Participants who were alive or lost to follow-up as of a data analysis cutoff date were right-censored. One month was considered 30.4375 days. OS (months) = (Date of Death/Censoring - Date of Randomization + 1)/30.4375

Outcome measures

Measure	Phase 1b Dose Determination: Entinostat Plus Atezolizumab n=40 Participants Participants received entinostat 5 mg on Days 1, 8, and 15 along with atezolizumab 1200 mg via intravenous (IV) infusion on Day 1 of Cycle 1 (21- day cycle).	Phase 2 Expansion: Placebo Plus Atezolizumab n=41 Participants Participants received placebo in combination with atezolizumab 1200 mg.
Phase 2 Expansion: Overall Survival (OS)	12.25 months Interval 5.49 to 21.16	11.20 months Interval 7.43 to 15.77

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data was not collected to estimate DOR using the prespecified Kaplan-Meier method for this outcome measure.

DOR was defined as the number of months from the date where a CR/PR (based on RECIST 1.1) or immune response CR (irCR)/immune response PR (irPR) was firstly observed, to the first date that recurrent or progressive disease was documented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data was not collected to estimate TTR using the prespecified Kaplan-Meier method for this outcome measure.

TTR was defined for the subset of participants that achieved best overall response of confirmed CR/PR or confirmed irCR/irPR as the number of months from date of randomization to date of the initial documented response of CR/PR (based on RECIST 1.1) or irCR/irPR (based on irRECIST).

Outcome measures

Outcome data not reported

Adverse Events

Phase 1 Dose Determination Phase: Entinostat Plus Atezolizumab

Serious events: 2 serious events

Other events: 8 other events

Deaths: 4 deaths

Phase 2 Expansion: Entinostat Plus Atezolizumab

Serious events: 18 serious events

Other events: 34 other events

Deaths: 20 deaths

Phase 2 Expansion: Placebo Plus Atezolizumab

Serious events: 14 serious events

Other events: 30 other events

Deaths: 21 deaths

Serious adverse events

Measure	Phase 1 Dose Determination Phase: Entinostat Plus Atezolizumab n=8 participants at risk Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Entinostat Plus Atezolizumab n=40 participants at risk Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Placebo Plus Atezolizumab n=39 participants at risk Participants received placebo in combination with atezolizumab 1200 mg.
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Blood and lymphatic system disorders Neutropenia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Cardiac Arrest	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Cardiac Tamponade	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Cardiopulmonary Failure	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Pericardial Effusion	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Sinus Tachycardia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Abdominal Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Haematochezia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Gait Disturbance	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Oedema Peripheral	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Pyrexia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Hepatobiliary disorders Biliary Obstruction	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Cellulitis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Infectious Mononucleosis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Pneumonia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Sepsis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Blood Bilirubin Increased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Dehydration	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain Neoplasm Malignant	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Encephalopathy	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Spinal Cord Compression	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Psychiatric disorders Mental Status Changes	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Vascular disorders Deep Vein Thrombosis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Vascular disorders Hypotension	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Vascular disorders Pelvic Venous Thrombosis	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).

Other adverse events

Measure	Phase 1 Dose Determination Phase: Entinostat Plus Atezolizumab n=8 participants at risk Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Entinostat Plus Atezolizumab n=40 participants at risk Participants received entinostat 5 mg in combination with atezolizumab 1200 mg.	Phase 2 Expansion: Placebo Plus Atezolizumab n=39 participants at risk Participants received placebo in combination with atezolizumab 1200 mg.
Blood and lymphatic system disorders Anaemia	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Blood and lymphatic system disorders Neutropenia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Blood and lymphatic system disorders Thrombocytopenia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Cardiac disorders Tachycardia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Endocrine disorders Hyperthyroidism	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.7% 3/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Eye disorders Vision Blurred	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Abdominal Pain	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Constipation	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Diarrhoea	37.5% 3/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Eructation	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Indigestion	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Loose Stool	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	12.5% 5/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Nausea	62.5% 5/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Nausea (Intermittent)	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Stomach Cramping	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Vomiting	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	22.5% 9/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	12.8% 5/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Gastrointestinal disorders Vomiting (Intermittent)	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Chills	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.7% 3/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Fatigue	75.0% 6/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Fever	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	20.0% 8/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	17.9% 7/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Flu Like Symptoms	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Lack of Energy	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Oedema	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Oedema Peripheral	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Pain	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Pyrexia	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
General disorders Weakness	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Nasopharyngitis	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Infections and infestations Urinary Tract Infection	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Injury, poisoning and procedural complications Fall	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.0% 2/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Alanine Aminotransferase Increased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Alkaline Phosphatase Increased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Decreased White Blood Count	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Increased Creatinine	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Neutrophil Count Decreased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Platelet Count Decreased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	17.5% 7/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Weight Decreased	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations Weight Loss	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Investigations White Blood Cell Count Decreased	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Anorexia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.7% 3/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Decreased Appetite	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Dehydration	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Hyponatraemia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Metabolism and nutrition disorders Loss of Appetite	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.7% 3/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Limb Mass	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Myalgia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Right Hip Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.7% 3/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Musculoskeletal and connective tissue disorders Right Leg Pain	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Dizziness	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Dygeusia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Headache	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	22.5% 9/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	17.9% 7/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Intermittent Headache	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	7.5% 3/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Nervous system disorders Taste Disturbance	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Psychiatric disorders Depressed Mood	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Psychiatric disorders Insomnia	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Reproductive system and breast disorders Breast Pain	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Cough	25.0% 2/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Dry Cough	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Shortness of Breath	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Respiratory, thoracic and mediastinal disorders Sore Throat	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	10.0% 4/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.6% 1/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Skin and subcutaneous tissue disorders Dry Skin	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Skin and subcutaneous tissue disorders Erythema Nodosum	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Skin and subcutaneous tissue disorders Rash	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Skin and subcutaneous tissue disorders Skin Burning Sensation	12.5% 1/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	0.00% 0/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).
Vascular disorders Hot Flashes	0.00% 0/8 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	2.5% 1/40 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).	5.1% 2/39 • 5 years All-cause mortality based upon all enrolled participants (ITT population), regardless of whether treatment was received. Serious and other adverse events based upon participants that received at least 1 dose of study drug (safety population).

Additional Information

Kate Madigan, MD, Chief Medical Officer

Syndax Pharmaceuticals, Inc.

Phone: 858-888-3798

Email: kmadigan@syndax.com

Results disclosure agreements

• Principal investigator is a sponsor employee Publication of the results of the multi-center Study shall not be made before the first multi-site publication by Sponsor or Publications Committee. No Public Presentation by Institution or Investigator will be made until Study Documentation/Results from all sites are received and analyzed by Sponsor. Separate publication by Investigator will be delayed for a period of 18 months until the initial publication by Committee or Sponsor, or a determination is made not to make such publication.
• Publication restrictions are in place

Restriction type: OTHER