Trial Outcomes & Findings for APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS) (NCT NCT03745716)

Last Updated: 2025-03-18

Results Overview

To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

154 participants

Primary outcome timeframe

12 months

Results posted on

2025-03-18

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental Arm: APR-246 + Azacitidine APR-246 4.5mg/day (D1-4 of 28 day cycle) Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Control Arm: Azacitidine Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)
Overall Study STARTED	78	76
Overall Study COMPLETED	75	74
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Arm: APR-246 + Azacitidine n=78 Participants APR-246 4.5mg/day (D1-4 of 28 day cycle) Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Control Arm: Azacitidine n=76 Participants Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Total n=154 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	56 Participants n=5 Participants	54 Participants n=7 Participants	110 Participants n=5 Participants
Age, Continuous	69 years n=5 Participants	69.5 years n=7 Participants	69 years n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	29 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	47 Participants n=7 Participants	89 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	58 Participants n=7 Participants	119 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	65 participants n=5 Participants	67 participants n=7 Participants	132 participants n=5 Participants
Region of Enrollment France	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: ITT

To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.

Outcome measures

Outcome measures
Measure	Experimental Arm: APR-246 + Azacitidine n=78 Participants APR-246 4.5mg/day (D1-4 of 28 day cycle) Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Control Arm: Azacitidine n=76 Participants Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)
Complete Response Rate (CR)	27 Participants	17 Participants

Adverse Events

Experimental Arm: APR-246 + Azacitidine

Serious events: 53 serious events

Other events: 76 other events

Deaths: 46 deaths

Control Arm: Azacitidine

Serious events: 38 serious events

Other events: 61 other events

Deaths: 36 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Medical Advisor

Aprea Therapeutics

Phone: 215-948-4119

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Experimental Arm: APR-246 + Azacitidine n=76 participants at risk APR-246 4.5mg/day (D1-4 of 28 day cycle) Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Control Arm: Azacitidine n=61 participants at risk Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Pneumonia	10.5% 8/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	13.1% 8/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Sepsis	6.6% 5/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	6.6% 4/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Septic shock	3.9% 3/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Cellulitis	2.6% 2/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Coronavirus infection	2.6% 2/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Skin infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Urinary tract infection	2.6% 2/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Abdominal infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Acute sinusitis	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Anal abscess	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Anorectal infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Bacterial sepsis	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Corynebacterium bacteremia	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Diverticulitis	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Enterobacter infection	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Escherichia bacteremia	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Herpes zoster	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Influenza	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Perirectal abscess	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Pneumonia fungal	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Pseudomonal bacteremia	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Pseudomonas infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Rhinovirus infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Sialadenitis	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Sinusitis	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Staphylococcal bacteremia	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Staphylococcal infection	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Thrombophlebitis septic	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Tooth infection	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Febrile neutropenia	32.9% 25/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	23.0% 14/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Anemia	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	3.3% 2/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	3.3% 2/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Febrile bone marrow aplasia	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Pyrexia	7.9% 6/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	6.6% 4/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Asthenia	2.6% 2/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders General physical health deterioration	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Hypothermia	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Injection site erythema	1.3% 1/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	0.00% 0/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).

Other adverse events
Measure	Experimental Arm: APR-246 + Azacitidine n=76 participants at risk APR-246 4.5mg/day (D1-4 of 28 day cycle) Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)	Control Arm: Azacitidine n=61 participants at risk Azacitidine 75mg/m2 (D4-D10 of 28 day cycle)
Gastrointestinal disorders Constipation	63.2% 48/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	52.5% 32/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Gastrointestinal disorders Nausea	67.1% 51/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	34.4% 21/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Gastrointestinal disorders Vomiting	52.6% 40/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	13.1% 8/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Gastrointestinal disorders Diarrhea	30.3% 23/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	27.9% 17/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Gastrointestinal disorders Stomatitis	15.8% 12/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Gastrointestinal disorders Abdominal pain	9.2% 7/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	14.8% 9/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Fatigue	39.5% 30/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	32.8% 20/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Pyrexia	27.6% 21/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	27.9% 17/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Injection site reaction	21.1% 16/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	27.9% 17/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Oedema peripheral	23.7% 18/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	23.0% 14/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
General disorders Chills	15.8% 12/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	16.4% 10/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Anemia	43.4% 33/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	44.3% 27/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Febrile neutropenia	40.8% 31/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	26.2% 16/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Neutropenia	21.1% 16/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	27.9% 17/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Blood and lymphatic system disorders Thrombocytopenia	23.7% 18/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	21.3% 13/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Investigations Neutrophil count decreased	44.7% 34/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	37.7% 23/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Investigations Platelet count decreased	32.9% 25/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	42.6% 26/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Investigations White blood cell count decreased	40.8% 31/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	47.5% 29/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Investigations Lymphocyte count decreased	18.4% 14/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	9.8% 6/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Nervous system disorders Headache	31.6% 24/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	21.3% 13/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Nervous system disorders Dizziness	31.6% 24/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	19.7% 12/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Nervous system disorders Paresthesia	18.4% 14/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Nervous system disorders Tremor	18.4% 14/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	1.6% 1/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Metabolism and nutrition disorders Hypokalemia	23.7% 18/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	19.7% 12/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Metabolism and nutrition disorders Decreased appetite	22.4% 17/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	18.0% 11/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Metabolism and nutrition disorders Hypoalbuminaemia	19.7% 15/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Metabolism and nutrition disorders Hyponatremia	15.8% 12/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	13.1% 8/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Metabolism and nutrition disorders Hypophosphatemia	18.4% 14/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Respiratory, thoracic and mediastinal disorders Dyspnea	18.4% 14/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	21.3% 13/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Respiratory, thoracic and mediastinal disorders Cough	21.1% 16/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	16.4% 10/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Infections and infestations Pneumonia	13.2% 10/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	14.8% 9/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 7/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	14.8% 9/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Musculoskeletal and connective tissue disorders Muscular weakness	14.5% 11/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Musculoskeletal and connective tissue disorders Back pain	13.2% 10/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Skin and subcutaneous tissue disorders Rash	15.8% 12/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	13.1% 8/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Skin and subcutaneous tissue disorders Pruritus	15.8% 12/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	8.2% 5/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Psychiatric disorders Insomnia	13.2% 10/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	14.8% 9/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Psychiatric disorders Confusional state	14.5% 11/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	23.0% 14/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Psychiatric disorders Anxiety	14.5% 11/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	14.8% 9/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).
Vascular disorders Hypotension	9.2% 7/76 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).	18.0% 11/61 • 12 months Treatment-Emergent Adverse Events (TEAEs) were defined as adverse events that occurred after the first dose of study medication up to 30 days after last dose. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade severity of TEAEs. Severity Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life-Threatening, 5= Fatal. SAE and AE data reported for Safety Evaluable population. (Experimental Arm n=76; Control Arm n=61).