Trial Outcomes & Findings for Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies (NCT NCT04214418)

Last Updated: 2024-12-18

Results Overview

The MTD is defined as the dose combination at which 30% of the patients experience a dose-limiting toxicity (DLT) by the end of Cycle 2

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

27 participants

Primary outcome timeframe

28 days

Results posted on

2024-12-18

Participant Flow

Of the 27 that signed a consent form, 12 were screen failures and one withdrew consent before randomization. A total of 14 participants were assigned to a treatment arm.

Participant milestones

Participant milestones
Measure	Phase I - Dose Level 1 Hydroxychloroquine 600 mg twice per day and Cobimetinib 40 mg once per day	Phase I - Dose Level 2 Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle
Overall Study STARTED	10	4
Overall Study COMPLETED	8	2
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I - Dose Level 1 Hydroxychloroquine 600 mg twice per day and Cobimetinib 40 mg once per day	Phase I - Dose Level 2 Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	0	2
Overall Study Death	1	0

Baseline Characteristics

Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I - Dose Level 1 n=10 Participants Hydroxychloroquine 600 mg twice per day and Cobimetinib 40 mg once per day	Phase I - Dose Level 2 n=4 Participants Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	2 Participants n=7 Participants	—	—	—	—	9 Participants n=8 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	—	—	—	—	5 Participants n=8 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	2 Participants n=7 Participants	—	—	—	—	8 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	—	—	—	—	6 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	1 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	4 Participants n=7 Participants	—	—	—	—	13 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	1 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	4 Participants n=7 Participants	—	—	—	—	13 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	—	—	—	0 Participants n=8 Participants
Region of Enrollment United States	10 participants n=5 Participants	4 participants n=7 Participants	—	—	—	—	14 participants n=8 Participants

PRIMARY outcome

Timeframe: 28 days

The MTD is defined as the dose combination at which 30% of the patients experience a dose-limiting toxicity (DLT) by the end of Cycle 2

Outcome measures

Outcome measures
Measure	All Participants n=14 Participants All participants to receive HCQ 600 mg twice a day	Phase I - Dose Level 2 Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1
Phase 1: Estimated Maximum Tolerated Dose (MTD) Hydroxychloroquine (HCQ)	600 mg	—	—	—	—	—

PRIMARY outcome

Timeframe: 28 days

The MTD is defined as the dose combination at which 30% of the patients experience a dose-limiting toxicity (DLT) by the end of Cycle 2

Outcome measures

Outcome measures
Measure	All Participants n=14 Participants All participants to receive HCQ 600 mg twice a day	Phase I - Dose Level 2 Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1
Phase 1: Estimated Maximum Tolerated Dose (MTD) Cobimetinib	40 mg	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 20 weeks

Population: Zero analyzed in the at Phase 1, dose level 3 and Phase 2 cohorts as the study terminated early and zero participants were assigned to these arms.

Adverse events (AEs) and serious adverse events (SAEs) that are deemed to be related to treatment

Outcome measures

Outcome measures
Measure	All Participants n=10 Participants All participants to receive HCQ 600 mg twice a day	Phase I - Dose Level 2 n=4 Participants Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1
Phase 1: Number of Participants With Treatment-Emergent Adverse Events	9 Participants	4 Participants	—	—	—	—

Adverse Events

Phase I - Dose Level 1

Serious events: 3 serious events

Other events: 10 other events

Deaths: 10 deaths

Phase I - Dose Level 2

Serious events: 1 serious events

Other events: 4 other events

Deaths: 4 deaths

Phase 1- Dose Level 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase 2: Cohort 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase 2: Cohort 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase 2: Cohort 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I - Dose Level 1 n=10 participants at risk Hydroxychloroquine 600 mg twice per day and Cobimetinib 40 mg once per day	Phase I - Dose Level 2 n=4 participants at risk Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Gastrointestinal disorders	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Hypokalemia	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Multi-organ failure	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Obstruction gastric	0.00% 0/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Nervous system disorders Stroke	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit

Other adverse events

Other adverse events
Measure	Phase I - Dose Level 1 n=10 participants at risk Hydroxychloroquine 600 mg twice per day and Cobimetinib 40 mg once per day	Phase I - Dose Level 2 n=4 participants at risk Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 1- Dose Level 3 Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg once per day, Atezolizumab 840mg on days 1 and 15 of each cycle	Phase 2: Cohort 1 Advanced Pancreatic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 2 Advanced Colorectal Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1	Phase 2: Cohort 3 Histology Agnostic Adenocarcinoma subjects will receive study treatment based on the MTD determined from Phase 1
Gastrointestinal disorders Abdominal pain	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Alanine aminotransferase increased	50.0% 5/10 • Up to 20 weeks Adverse events collected systematically at each visit	50.0% 2/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Acidosis	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Alkaline phosphatase increased	30.0% 3/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Alopecia	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Blood and lymphatic system disorders Anemia	30.0% 3/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Anorexia	30.0% 3/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Ascites	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Aspartate aminotransferase increased	60.0% 6/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Blood bilirubin increased	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	50.0% 2/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Blood lactate dehydrogenase increased	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Bullous dermatitis	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Chills	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Constipation	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Creatinine Phosphokinase Increased	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Creatinine increased	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Diarrhea	60.0% 6/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Nervous system disorders Dizziness	0.00% 0/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Dry mouth	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Dyspepsia	0.00% 0/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Edema face	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Edema limbs	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Cardiac disorders Ejection fraction decreased	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Eye disorders Eye disorders	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Fatigue	50.0% 5/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Fever	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Flatulence	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Gastrointestinal disorders	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Nervous system disorders Headache	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Infections and infestations Hepatic infection	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Respiratory, thoracic and mediastinal disorders Hoarseness	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Hypoalbuminemia	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Metabolism and nutrition disorders Hypoglycemia	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Vascular disorders Hypotension	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Lower gastrointestinal hemorrhage	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Lymphocyte count decreased	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Cardiac disorders Myocardial infarction	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Nausea	40.0% 4/10 • Up to 20 weeks Adverse events collected systematically at each visit	50.0% 2/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Neutrophil count decreased	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Non-cardiac chest pain	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
General disorders Pain	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Papulopustular rash	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Investigations Platelet count decreased	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Respiratory, thoracic and mediastinal disorders Pneumothorax	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Pruritus	30.0% 3/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Psychiatric disorders Psychiatric disorders	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Rash acneiform	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Rash maculo-papular	30.0% 3/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Infections and infestations Sepsis	20.0% 2/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Infections and infestations Thrush	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Renal and urinary disorders Urinary retention	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Infections and infestations Urinary tract infection	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Renal and urinary disorders Urinary tract obstruction	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Renal and urinary disorders Urine discoloration	10.0% 1/10 • Up to 20 weeks Adverse events collected systematically at each visit	0.00% 0/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit
Gastrointestinal disorders Vomiting	70.0% 7/10 • Up to 20 weeks Adverse events collected systematically at each visit	25.0% 1/4 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit	— 0/0 • Up to 20 weeks Adverse events collected systematically at each visit

Additional Information

Gulam Manji, MD, PhD

Columbia University

Phone: 212-304-6357

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the information provided by the sponsor for the purposes of performing the study, will be published or passed on to any third party without the consent of the study sponsor. Any investigator involved with this study is obligated to provide the sponsor with complete test results and all data derived from the study.
Publication restrictions are in place

Restriction type: OTHER