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

Phase IIIb, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Previously Untreated Unresectable or Metastatic Melanoma

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

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia
      • Melanoma Institute Australia
  • Queensland
    • Greenslopes, Queensland, Australia
      • Greenslopes Private Hospital
  • Victoria
    • Malvern, Victoria, Australia
      • Cabrini Hospital
• France
  • Lyon Cedex 08, France, 69373
    • Local Institution
  • Marseille Cedex 5, France, 13385
    • Hopital de la Timone
  • Nantes Cedex 1, France, 44093
    • Local Institution
  • Paris, France, 75475
    • Hôpital Saint Louis
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Tours, France, 37044
    • Hôpital Trousseau - CHRU Tours
• Italy
  • Genova, Italy, 16128
    • Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med
  • Meldola (FC), Italy, 47014
    • Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Torino, Italy, 10137
    • Azienda Ospedaliera Citta della Salute e della Scienza
• Spain
  • Barcelona, Spain, 08036
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Sevilla, Spain, 41071
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab and Ipilimumab Concomitant Administration; Followed by Nivolumab monotherapy	Biological: Nivolumab; -Specified dose on specified days; Biological: Ipilimumab; -Specified dose on specified days
Experimental: Nivolumab and Ipilimumab Sequential Administration; Followed by Nivolumab monotherapy	Biological: Nivolumab; -Specified dose on specified days; Biological: Ipilimumab; -Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)	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.	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ	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.	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs	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	Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs	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	From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs	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	From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
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.
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 Ipilimumab		From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Geometric Mean Trough Concentration of Nivolumab		From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Objective Response Rate (ORR)	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.	Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)
Progression Free Survival (PFS)	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.	From the date of randomization to the first date of documented progression (approximately 26 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2016
• Primary Completion (Actual): October 23, 2017
• Study Completion (Actual): October 25, 2019

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimate): September 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-742; 2016-001941-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes