Trial Outcomes & Findings for KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer (NCT NCT03342937)

Last Updated: 2024-03-13

Results Overview

PFS measured from study entry until documented progression or death from any cause. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Patients who have not experienced progression will be censored at the date of the last radiographic assessment. The median PFS will be estimated using the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Up to 44 months

Results posted on

2024-03-13

Participant Flow

Subjects recruited at Duke University Medical Center and Lexington Medical Center.

36 subjects consented and received the study drugs. 6 subjects received study drugs in the safety run-in. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.

Participant milestones

Participant milestones
Measure	Oxaliplatin + Capecitabine + Pembrolizumab For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose expansion: Cycle 1 is 28 days. Cycle 2 and beyond are 21 days.
Overall Study STARTED	36
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=36 Participants For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Age, Continuous	59.1 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 44 months

Population: The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined. One treated patient did not complete cycle 1 of therapy.

Outcome measures

Outcome measures
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=35 Participants For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Months of Progression-free Survival (PFS)	7.6 months Interval 5.8 to 11.2

SECONDARY outcome

Timeframe: Up to 44 months

Population: Treated patients with at least 1 re-staging. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.

Response rate is calculated as the number of people with a complete response or partial response, divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=33 Participants For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Response Rate as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	0.76 proportion of participants Interval to 0.9

SECONDARY outcome

Timeframe: Up to 44 months

Overall survival is the amount of time subjects live since starting the study.

Outcome measures

Outcome measures
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=36 Participants For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Months of Overall Survival	16 months Interval 11.6 to 24.3

Adverse Events

Oxaliplatin + Capecitabine + Pembrolizumab

Serious events: 17 serious events

Other events: 36 other events

Deaths: 26 deaths

Serious adverse events

Serious adverse events
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=36 participants at risk For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Cardiac disorders Pericardial tamponade	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Cardiac disorders Sinus tachycardia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Abdominal pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Ascites	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Colitis	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Colonic obstruction	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Constipation	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Diarrhea	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Dysphagia	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Nausea	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Vomiting	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Sudden death NOS	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Device related infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Enterocolitis infectious	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Infections and infestations - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Lung infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Meningitis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Sepsis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Aspartate aminotransferase increased	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Dehydration	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hyperglycemia	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Bone pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Vascular disorders Thromboembolic event	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.

Other adverse events

Other adverse events
Measure	Oxaliplatin + Capecitabine + Pembrolizumab n=36 participants at risk For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days 1-14, Pembrolizumab 200 mg IV on Day 1. Safety validation: all Cycles are 21 days in length. Dose Expansion: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Blood and lymphatic system disorders Anemia	38.9% 14/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Cardiac disorders Sinus tachycardia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Ear and labyrinth disorders Vertigo	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Endocrine disorders Adrenal insufficiency	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Endocrine disorders Endocrine disorders - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Endocrine disorders Hyperthyroidism	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Endocrine disorders Hypothyroidism	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Abdominal distension	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Abdominal pain	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Ascites	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Bloating	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Colitis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Constipation	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Diarrhea	36.1% 13/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Dry mouth	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Dyspepsia	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Dysphagia	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Esophageal pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Esophagitis	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Fecal incontinence	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Flatulence	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Gastroesophageal reflux disease	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Gastrointestinal disorders - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Mucositis oral	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Nausea	41.7% 15/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Toothache	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Gastrointestinal disorders Vomiting	27.8% 10/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Edema limbs	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Fatigue	38.9% 14/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Fever	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Gait disturbance	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Localized edema	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Malaise	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Non-cardiac chest pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
General disorders Pain	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Hepatobiliary disorders Hepatobiliary disorders - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Immune system disorders Allergic reaction	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Esophageal infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Eye infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Lung infection	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Otitis externa	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Otitis media	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Sinusitis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Skin infection	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Upper respiratory infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Urinary tract infection	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Infections and infestations Wound infection	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Injury, poisoning and procedural complications Bruising	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Injury, poisoning and procedural complications Venous injury	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Alanine aminotransferase increased	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Alkaline phosphatase increased	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Aspartate aminotransferase increased	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Blood bilirubin increased	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Creatinine increased	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations INR increased	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Lymphocyte count decreased	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Neutrophil count decreased	30.6% 11/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Platelet count decreased	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Weight gain	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations Weight loss	25.0% 9/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Investigations White blood cell decreased	25.0% 9/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Anorexia	41.7% 15/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Dehydration	19.4% 7/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hyperglycemia	19.4% 7/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hyperkalemia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hypoalbuminemia	30.6% 11/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hypocalcemia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hypoglycemia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hypokalemia	16.7% 6/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hyponatremia	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Hypophosphatemia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Arthritis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Flank pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Dizziness	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Dysesthesia	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Dysgeusia	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Paresthesia	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Peripheral sensory neuropathy	36.1% 13/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Presyncope	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Nervous system disorders Syncope	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Psychiatric disorders Anxiety	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Psychiatric disorders Insomnia	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Renal and urinary disorders Cystitis noninfective	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Renal and urinary disorders Urinary frequency	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Renal and urinary disorders Urinary incontinence	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Renal and urinary disorders Urinary retention	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Reproductive system and breast disorders Erectile dysfunction	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Reproductive system and breast disorders Pelvic pain	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Cough	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Hiccups	8.3% 3/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Hoarseness	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Sore throat	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Voice alteration	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Respiratory, thoracic and mediastinal disorders Wheezing	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Dry skin	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Nail loss	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	30.6% 11/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Pruritus	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 4/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Specify	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Skin hypopigmentation	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Skin and subcutaneous tissue disorders Skin ulceration	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Vascular disorders Hypertension	16.7% 6/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Vascular disorders Hypotension	5.6% 2/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Vascular disorders Superficial thrombophlebitis	2.8% 1/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.
Vascular disorders Thromboembolic event	13.9% 5/36 • From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months). All grade 2-5 adverse events will be recorded in the study database. The safety run-in was intended to identify dose-limiting toxicity. No DLTs were observed in the safety run-in and the drug dose levels were not changed in the expansion cohort, therefore; results were for safety validation and expansion were combined.

Additional Information

Dr. Hope Uronis

Duke University

Phone: 919-668-1861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place