Trial Outcomes & Findings for Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC (NCT NCT03256136)

Last Updated: 2020-11-04

Results Overview

Complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Up to approximately 2 years

Results posted on

2020-11-04

Participant Flow

Participant milestones

Participant milestones
Measure	Nivolumab Plus Ipilimumab EGFR Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Overall Study STARTED	3	1	4	1
Overall Study COMPLETED	3	1	4	1
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Total n=9 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
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 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
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 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
Race (NIH/OMB) Black or African American	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
Race (NIH/OMB) White	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 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
Race (NIH/OMB) Unknown or Not Reported	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
Region of Enrollment United States	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	1 participants n=4 Participants	9 participants n=21 Participants
Treatment Regimen Received	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to approximately 2 years

Outcome measures

Outcome measures
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Objective Response Rate (ORR), Presented in Numbers of Participants	0 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to approximately 2 years

The number of patients that achieved either complete response (CR), partial response (PR), or stable disease (SD) per RECIST version 1.1 * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Disease Control Rate (DCR), Presented in Numbers of Participants	0 Participants	0 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From the start of treatment until disease progression or death due to any cause, up to approximately 2 years

Time from initiation of the study drugs to progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1 Progressive Disease (PD): 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. (Note:the appearance of one or more new lesions is also considered progression). Confidence Intervals (CIs) were calculated using the Kaplan Meier (KM) method

Outcome measures

Outcome measures
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Progression Free Survival (PFS)	1.3 months Interval 0.6 to 1.4	0.7 months confidence interval is not defined due to an insufficient number of events	4.65 months Interval 1.2 to 8.4	2.8 months confidence interval is not defined due to an insufficient number of events

SECONDARY outcome

Timeframe: From the start of treatment until death due to any cause, up to approximately 2 years

Time from initiation of the study drugs to date of death due to any cause. CIs are the KM estimate CIs.

Outcome measures

Outcome measures
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Overall Survival (OS)	22.3 months Interval 2.6 to 23.7	7.6 months confidence interval is not defined due to an insufficient number of events	7.75 months Interval 2.1 to 16.2	15.9 months confidence interval is not defined due to an insufficient number of events

SECONDARY outcome

Timeframe: From the first documented response until disease progression or death, up to approximately 2 years

Time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Progressive Disease (PD): 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. (Note:the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Nivolumab Plus Ipilimumab EGFR n=3 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 Participants Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 Participants Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Duration Of Response	NA months no objective responses in this cohort	NA months no objective responses in this cohort	0.9 months confidence interval is not defined due to an insufficient number of events	1.4 months confidence interval is not defined due to an insufficient number of events

Adverse Events

Nivolumab Plus Ipilimumab EGFR

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Nivolumab Plus Ipilimumab ALK

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive

Serious events: 3 serious events

Other events: 4 other events

Deaths: 2 deaths

Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab Plus Ipilimumab EGFR n=3 participants at risk Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab Plus Ipilimumab ALK n=1 participants at risk Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks Nivolumab: will allow the body's immune system to work against tumor cells Ipilimumab: will allow the body's immune system to work against tumor cells	Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive n=4 participants at risk Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy	Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive n=1 participants at risk Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks Carboplatin: Chemotherapy Nivolumab: will allow the body's immune system to work against tumor cells pemetrexed: Chemo therapy
Investigations Blood bilirubin increase	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	100.0% 1/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Infections and infestations Skin infection	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Nervous system disorders Seizure	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Blood and lymphatic system disorders Anemia	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Blood and lymphatic system disorders Neutrophil count decrease	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Ear and labyrinth disorders Vertigo	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	25.0% 1/4 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years	0.00% 0/1 • From the start of treatment until 30 days after the end of treatment, up to approximately 2 years

Other adverse events

Additional Information

Dr. Jessica Lin

Massachusetts General Hospital

Phone: 617-724-1134

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place