Trial Outcomes & Findings for Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy (NCT NCT02731729)

Last Updated: 2022-12-23

Results Overview

Overall Response Rate was defined as any participant who had a Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1 by week 18 of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Week 18

Results posted on

2022-12-23

Participant Flow

Participants were recruited at four institutions in the United States. Recruitment occurred between June 2016 to May 2018.

33 participants were assessed for eligibility. Out of the 33 participants, 20 patients met the inclusion/exclusion criteria and were randomized to the study arms.

Participant milestones

Participant milestones
Measure	Ipilimumab and Nivolumab For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Overall Study STARTED	10	10
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	9	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Ipilimumab and Nivolumab For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Overall Study Death	2	2
Overall Study Study terminated by Sponsor	6	6
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab	Total n=19 Participants Total of all reporting groups
Age, Continuous	66 years n=5 Participants	56 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
ECOG Performance Status ECOG Score = 0	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
ECOG Performance Status ECOG Score = 1	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
M stage M0	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
M stage M1a	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
M stage M1b	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
M stage M1c - without brain metastases	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Type of Melanoma Acral	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Type of Melanoma Cutaneous	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Type of Melanoma Mucosal	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Genomic Driver v-RAF murine sarcoma viral oncogene homolog B1 (BRAF)	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Genomic Driver Neuroblastoma RAS viral oncogene homolog (NRAS)	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Genomic Driver Other/Unknown	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Prior Treatment Anti-PD-1	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Prior Treatment Other	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Best response to prior anti-PD-1 treatment Stable Disease	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Best response to prior anti-PD-1 treatment Progressive Disease	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Best response to prior anti-PD-1 treatment Unknown	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Median lactate dehydrogenase	214 units/L n=5 Participants	208 units/L n=7 Participants	211 units/L n=5 Participants
Median time since last anti-PD-1 treatment	4.3 weeks n=5 Participants	6.0 weeks n=7 Participants	5.1 weeks n=5 Participants

PRIMARY outcome

Timeframe: Week 18

Population: Efficacy-Evaluable Population. The efficacy-evaluable population includes all participants who were randomly allocated to receive either combination ipilimumab/nivolumab or ipilimumab alone and received at least one dose of any study intervention (ipilimumab or nivolumab). For analyses based on this population, participant treatment groups are defined according to the treatment that was assigned at randomization.

Overall Response Rate was defined as any participant who had a Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1 by week 18 of treatment.

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Overall Response Rate (ORR) as Defined by RECIST v1.1 at Week 18	20 percentage of participants Interval 3.0 to 56.0	56 percentage of participants Interval 21.0 to 86.0

SECONDARY outcome

Timeframe: Week 18

Disease Control Rate was defined as any participant who achieved a complete response (CR), partial response (PR), or who remained stable (SD) as defined in Recist v1.1 at week 18.

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Disease Control Rate (DCR) Status at Week 18	60 percentage of participants Interval 26.0 to 88.0	67 percentage of participants Interval 30.0 to 93.0

SECONDARY outcome

Timeframe: The time from treatment initiation until a subsequent therapy is started or death.

Time to Treatment Failure is defined as the time from treatment initiation until the participant starts a subsequent therapy or death, whichever comes first.

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Time to Treatment Failure (TTF)	26.9 months Interval 0.7 to The upper confidence limit is not evaluable based on the available data	13.6 months Interval 2.8 to The upper confidence limit is not evaluable based on the available data

SECONDARY outcome

Timeframe: Death

Overall Survival is defined as the time of treatment initiation to death by any cause

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Overall Survival (OS)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: AE were monitored during each treatment cycle and could be reported until 30 days after the last dose of study treatment had been administered.

Population: Safety-Evaluable Population. The safety-evaluable population includes all participants who received at least one dose of any study intervention. For analyses based on this population, participant treatment groups will be defined according to the treatment that was assigned at randomization. However, if a participant received the incorrect study drug for the entire period of treatment, the participant's treatment group will be defined as the treatment the participant actually received.

The occurrence of Grade 3 and Grade 4 adverse events (AE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Number of Participants With Grade 3 or 4 Adverse Events	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Week 12

Disease Control Rate was defined as any participant who achieved a complete response (CR), partial response (PR), or who remained stable (SD) as defined in Recist v1.1 at week 12.

Outcome measures

Outcome measures
Measure	Ipilimumab and Nivolumab n=10 Participants For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 Participants In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Disease Control Rate (DCR) Status at Week 12	60.0 Percentage of participants Interval 26.2 to 87.8	55.6 Percentage of participants Interval 21.2 to 86.3

Adverse Events

Ipilimumab and Nivolumab

Serious events: 2 serious events

Other events: 10 other events

Deaths: 2 deaths

Ipilimumab

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Ute Dugan

Parker Institute for Cancer Immunotherapy

Phone: 203-379-6757

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Trial Site and/or Co-Principal Investigators may publish or present Study Data and other results of the Study from the Trial Site individually upon the first to occur of: (i) twelve (12) months after conclusion, abandonment, or termination of the Study at all Affiliated Research Institutions, or (ii) after Parker Institute for Cancer Immunotherapy \[PICI\] confirms in writing there will not be a multi-site Study publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ipilimumab and Nivolumab n=10 participants at risk For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes. ipilimumab nivolumab	Ipilimumab n=9 participants at risk In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses. ipilimumab
Gastrointestinal disorders Colitis	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	22.2% 2/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Gastrointestinal disorders Vomiting	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	0.00% 0/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Psychiatric disorders Confusional state	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	22.2% 2/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Vascular disorders Hypertension	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Vascular disorders Hypotension	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	0.00% 0/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Cardiac disorders Pericardial effusion	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	0.00% 0/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Endocrine disorders Adrenal insufficiency	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Infections and infestations Urinary tract infection	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Investigations Neutrophil count decreased	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Investigations White blood cell count decreased	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Nervous system disorders Headache	0.00% 0/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	0.00% 0/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Reproductive system and breast disorders Pleural effusion	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	0.00% 0/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.
Gastrointestinal disorders Nausea	10.0% 1/10 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.	11.1% 1/9 • Adverse events were monitored during each cycle. Adverse events were reported until 30 days after the last dose of study treatment had been administered.