A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma

Phase 3

Completed

• Conditions: Melanoma
• Interventions: Biological: Nivolumab; Biological: Ipilimumab

• Registration Number: NCT02905266
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

This is a safety and efficacy study of different administration regimens of nivolumab plus Ipilimumab in subjects with previously untreated, unresectable or metastatic melanoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-09-14
• Study First Submitted QC: 2016-09-14
• Study First Posted: 2016-09-19
• Study Start: 2016-10-27
• Primary Completion: 2017-10-23
• Results First Submitted: 2018-10-23
• Results First Submitted QC: 2018-12-18
• Results First Posted: 2019-01-08
• Study Completion: 2019-10-25
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-19
• Last Update Posted: 2020-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

• Males and Females, ages 15 years ≥ of age (Except where local regulations and/or institutional policies do not allow for subjects < 18 years of age to participate)
• Subjects must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma that is unresectable or metastatic
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Subjects have not been treated by systemic anticancer therapy for unresectable or metastatic melanoma

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Exclusion Criteria

• Subjects with active brain metastases or leptomeningeal metastases
• Subjects with ocular melanoma
• Subjects with active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nivolumab and Ipilimumab Concomitant Administration	Ipilimumab	Followed by Nivolumab monotherapy
Nivolumab and Ipilimumab Sequential Administration	Ipilimumab	Followed by Nivolumab monotherapy
Nivolumab and Ipilimumab Concomitant Administration	Nivolumab	Followed by Nivolumab monotherapy
Nivolumab and Ipilimumab Sequential Administration	Nivolumab	Followed by Nivolumab monotherapy

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)	This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)	This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.
Geometric Mean Trough Concentration of Ipilimumab	From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Objective Response Rate (ORR)	Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)	The ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
Progression Free Survival (PFS)	From the date of randomization to the first date of documented progression (approximately 26 months)	PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first.
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs	From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)	This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)	From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported
Geometric Mean Trough Concentration of Nivolumab	From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)	This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs	From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)	This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)	From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported.

Trial Locations

Locations (11)

Cabrini Hospital; 🇦🇺 Malvern, Victoria, Australia

Hopital Saint Louis; 🇫🇷 Paris, France

Local Institution; 🇪🇸 Sevilla, Spain

Hopital De La Timone; 🇫🇷 Marseille Cedex 5, France

Melanoma Institute Australia; 🇦🇺 North Sydney, New South Wales, Australia

Greenslopes Private Hospital; 🇦🇺 Greenslopes, Queensland, Australia

Hopital Trousseau - Chru Tours; 🇫🇷 Tours, France

Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med; 🇮🇹 Genova, Italy

Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori; 🇮🇹 Meldola (FC), Italy

Istituto Europeo Di Oncologia; 🇮🇹 Milan, Italy

Azienda Ospedaliera Citta della Salute e della Scienza; 🇮🇹 Torino, Italy