Trial Outcomes & Findings for Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer (NCT NCT03468985)

Last Updated: 2023-10-17

Results Overview

Progression-free survival is defined as time from randomization to documented disease progression or death from any cause, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions and/or at least a 20% increase in the sum of the 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. PFS will be estimated using the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Every 3 months up to 4 years and 2 months

Results posted on

2023-10-17

Participant Flow

The study was activated on March 1, 2018 and closed on May 31, 2019 for a total of 3 patients enrolled on this study. Patients were randomized to 1 of 3 arms (arms A, B and C). Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement were assigned to Arm T.

Participant milestones

Participant milestones
Measure	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	1	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	0	0	2	0
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) n=2 Participants Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) n=1 Participants Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=3 Participants Total of all reporting groups
Age, Continuous	—	78 years n=7 Participants	—	53 years n=4 Participants	75 years n=21 Participants
Sex: Female, Male Female	—	2 Participants n=7 Participants	—	1 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	1 Participants n=7 Participants	—	1 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	—	1 Participants n=7 Participants	—	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	—	2 Participants n=7 Participants	—	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) More than one race	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Every 3 months up to 4 years and 2 months

Population: All patients enrolled are included in this analysis.

Outcome measures

Outcome measures
Measure	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) n=2 Participants Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) n=1 Participants Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	—	6.35 months Interval 3.3 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	—	14.3 months Only one patient was enrolled on Arm T so 95% confidence interval was not calculable.

SECONDARY outcome

Timeframe: Every 3 months up to 4 years and 2 months

Population: All patients enrolled are included in this analysis.

Overall survival is defined as time from randomization to death or date last known alive.

Outcome measures

Outcome measures
Measure	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) n=2 Participants Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) n=1 Participants Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	—	11.85 months Interval 11.7 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	—	NA months The only patient in Arm T was still alive as of the final analysis so median overall survival was not reached and 95% confidence intervals were not calculable.

SECONDARY outcome

Timeframe: Every 3 months up to 4 years and 2 months

Population: All enrolled patients are included in this analysis.

Best overall response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response is defined as either complete response (CR) or partial response (PR). Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. For Arm T patients, to be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. Arm A, B, and C patients do not require confirmation scans for CR or PR.

Outcome measures

Outcome measures
Measure	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) n=2 Participants Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) n=1 Participants Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Best Overall Response Response (CR or PR)	—	0 Participants	—	0 Participants
Best Overall Response No Response (Other)	—	2 Participants	—	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Every 3 months for 5 years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Every 3 months for 5 years

Best overall response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Response is defined as either complete response (CR) or partial response (PR). Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Response by iRRC is defined as per RECIST1.1. Measurements of iRECIST response will be performed as described by Seymour et al with time point and over all response assessments categorized as immune complete response (iCR), immune partial response (iPR), immune stable disease (iSD), immune unconfirmed progressive disease (iUPD) and confirmed progressive disease (iCPD).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Every 3 months for 5 years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 4 weeks until 30 days after treatment completion, up to 5 years

A combined analysis of the data from the selected Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN) trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 3 months and 6 months

A combined analysis of the data from the selected ECOG-ACRIN trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report. Psychological Symptom Assessment: Anxiety \& Depression: (The Patient Reported Outcomes Measurement Information System (PROMIS®)). The 4-item Short Form PROMIS® for anxiety and depression will be administered. Score ranges between 4 and 20. Higher scores indicate more anxiety/depression. Physical Symptom Assessment by Functional Assessment of Chronic Illness Therapy (FACIT): Six symptom items (general pain, fatigue, nausea, cough, sleep difficulties, shortness of breath) from FACIT will be used for evaluation. Score ranges between 5 and 20. Higher scores indicate higher shame.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 3 months and 6 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months for 5 years

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Nivolumab)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm B (Nivolumab, Cabozantinib)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Arm C (Nivolumab, Cabozantinib, Ipilimumab)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm T (Targeted Cohort; Nivolumab, Cabozantinib)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (Nivolumab) Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Nivolumab, Cabozantinib) n=2 participants at risk Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Nivolumab, Cabozantinib, Ipilimumab) Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm T (Targeted Cohort; Nivolumab, Cabozantinib) n=1 participants at risk Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
General disorders Fatigue	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	100.0% 1/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Investigations Alanine aminotransferase increased	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Investigations Aspartate aminotransferase increased	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	100.0% 2/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Investigations Lymphocyte count decreased	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Investigations Neutrophil count decreased	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	100.0% 1/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Metabolism and nutrition disorders Hypokalemia	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Metabolism and nutrition disorders Hyponatremia	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Musculoskeletal and connective tissue disorders Arthralgia	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	100.0% 1/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Musculoskeletal and connective tissue disorders Arthritis	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.
Vascular disorders Hypertension	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	— 0/0 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 4 years and 2 months Serious adverse events are defined as grade 3 or higher adverse events that are possibly, probably, or definitely related to protocol therapy. Other adverse events are defined as grade 1 or grade 2 adverse events that are possibly, probably, or definitely related to protocol therapy with a frequency of at least 5% in a given arm. All patients enrolled are included in all-cause mortality analysis. Patients who received treatment with adverse event data available are included in AE analysis.

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60