Trial Outcomes & Findings for Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib (NCT NCT02155465)

NCT ID: NCT02155465

Last Updated: 2019-01-16

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2019-01-16

Participant Flow

Participant milestones

Measure	Phase 1: Level 1 Level 1 (10mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	Phase 1: Level 2 Level 2 (15mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	Phase 1: Level 3 Level 3 (20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	PHASE 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Overall Study STARTED	3	3	6	2	1	2	5
Overall Study COMPLETED	3	3	6	2	1	2	5
Overall Study NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib

Baseline characteristics by cohort

Measure	Phase 1: Level 1 n=3 Participants Level 1 (10mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	Phase 1: Level 2 n=3 Participants Level 2 (15mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	Phase 1: Level 3 n=6 Participants Level 3 (20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib)	Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD n=2 Participants 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd n=1 Participants 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd n=2 Participants 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd n=5 Participants 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd	Total n=22 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	3 Participants n=115 Participants	12 Participants n=6 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	2 Participants n=115 Participants	10 Participants n=6 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants	13 Participants n=6 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	9 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	2 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=6 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	4 Participants n=115 Participants	17 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	5 Participants n=115 Participants	22 Participants n=6 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Maximally Tolerated Dose (MTD) is determined by evaluating all Phase I participants as a whole. All Phase I participants are evaluated together to determine the MTD.

Outcome measures

Measure	Phase I Participants n=12 Participants Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made.	Phase II Participants Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily.	Phase 1: Level 3 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	Phase 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Maximally Tolerated Dose (MTD) (Phase I) Erlotinib Daily	150 mg	—	—	—	—	—	—
Maximally Tolerated Dose (MTD) (Phase I) Ruxolitinib Twice Daily	20 mg	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 1 year

Population: Participants response to study treatment were combined and evaluated to determine an overall response rate.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), at least a 20% increase in the sum of the diameter of the target lesions or the appearance of one or more new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

Outcome measures

Measure	Phase I Participants n=22 Participants Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made.	Phase II Participants Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily.	Phase 1: Level 3 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	Phase 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Assess Overall Response Rate	5 % of participants with partial response Interval 0.0 to 13.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 2 years

Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.

Outcome measures

Measure	Phase I Participants n=3 Participants Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made.	Phase II Participants n=3 Participants Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily.	Phase 1: Level 3 n=6 Participants 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD n=2 Participants 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	Phase 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd n=1 Participants 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd n=2 Participants 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd n=5 Participants 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Number of Participants With NCI CTCAE Toxicity	3 Participants	3 Participants	6 Participants	2 Participants	1 Participants	2 Participants	5 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Participants response to study treatment were combined and evaluated to determine an overall progression-free survival.

Outcome measures

Measure	Phase I Participants n=22 Participants Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made.	Phase II Participants Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily.	Phase 1: Level 3 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	Phase 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Progression-free Survival	2.2 months Interval 1.5 to 4.1	—	—	—	—	—	—

Adverse Events

Phase 1: Level 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Phase 1: Level 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 1: Level 3

Serious events: 2 serious events

Other events: 5 other events

Deaths: 5 deaths

PHASE 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD

Serious events: 0 serious events

Other events: 2 other events

Deaths: 2 deaths

PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd

Serious events: 1 serious events

Other events: 5 other events

Deaths: 3 deaths

Serious adverse events

Measure	Phase 1: Level 1 n=3 participants at risk 10mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 1: Level 2 n=3 participants at risk 15mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 1: Level 3 n=6 participants at risk 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	PHASE 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD n=2 participants at risk 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd n=1 participants at risk 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd n=2 participants at risk 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd n=5 participants at risk 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Blood and lymphatic system disorders Anemia	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Cardiac disorders Atrial fibrillation	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Psychiatric disorders Confusion	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Gastrointestinal disorders Diarrhea	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	100.0% 1/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Fatigue	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Fever	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Gastrointestinal disorders Nausea	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms ben/mal/unk (inc cyst/polyp) Other, spec	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years
General disorders Non-cardiac chest pain	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	100.0% 1/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Cardiac disorders Pericardial effusion	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	100.0% 1/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Vascular disorders Thromboembolic event	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Gastrointestinal disorders Vomiting	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years

Other adverse events

Measure	Phase 1: Level 1 n=3 participants at risk 10mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 1: Level 2 n=3 participants at risk 15mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	Phase 1: Level 3 n=6 participants at risk 20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib	PHASE 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD n=2 participants at risk 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD	PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd n=1 participants at risk 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd n=2 participants at risk 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd	PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd n=5 participants at risk 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years
Blood and lymphatic system disorders Anemia	66.7% 2/3 • 2 years	100.0% 3/3 • 2 years	33.3% 2/6 • 2 years	100.0% 2/2 • 2 years	100.0% 1/1 • 2 years	50.0% 1/2 • 2 years	40.0% 2/5 • 2 years
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations Alkaline phosphatase increased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	33.3% 2/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations Aspartate aminotransferase increased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations White blood cell decreased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	33.3% 2/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	50.0% 1/2 • 2 years	20.0% 1/5 • 2 years
Investigations Blood bilirubin increased	0.00% 0/3 • 2 years	66.7% 2/3 • 2 years	0.00% 0/6 • 2 years	50.0% 1/2 • 2 years	100.0% 1/1 • 2 years	0.00% 0/2 • 2 years	20.0% 1/5 • 2 years
Investigations Alanine aminotransferase increased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • 2 years	33.3% 1/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations Lymphocyte count decreased	0.00% 0/3 • 2 years	66.7% 2/3 • 2 years	50.0% 3/6 • 2 years	0.00% 0/2 • 2 years	100.0% 1/1 • 2 years	50.0% 1/2 • 2 years	20.0% 1/5 • 2 years
Gastrointestinal disorders Diarrhea	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Fatigue	66.7% 2/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations Neutrophil count decreased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	50.0% 3/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	50.0% 1/2 • 2 years	20.0% 1/5 • 2 years
Gastrointestinal disorders Constipation	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Musculoskeletal and connective tissue disorders Pain	66.7% 2/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	50.0% 1/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	50.0% 1/2 • 2 years	20.0% 1/5 • 2 years
Metabolism and nutrition disorders Hypernatremia	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Investigations INR increased	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	50.0% 1/2 • 2 years	0.00% 0/5 • 2 years
General disorders Chills	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	100.0% 1/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Cardiac disorders Atrial fibrillation	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Infections and infestations Conjunctivitis	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Ear and labyrinth disorders Ear pain	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Fever	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Flu like symptoms	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Gastrointestinal disorders Gastritis	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Ear and labyrinth disorders Hearing impaired	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Localized edema	0.00% 0/3 • 2 years	0.00% 0/3 • 2 years	16.7% 1/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
General disorders Non-cardiac chest pain	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Cardiac disorders Pericardial effusion	33.3% 1/3 • 2 years	0.00% 0/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Infections and infestations Sinusitis	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years
Vascular disorders Thromboembolic event	0.00% 0/3 • 2 years	33.3% 1/3 • 2 years	0.00% 0/6 • 2 years	0.00% 0/2 • 2 years	0.00% 0/1 • 2 years	0.00% 0/2 • 2 years	0.00% 0/5 • 2 years

Additional Information

Dr. Helena Yu, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4274

Email: YuH@mskcc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place