MelanomaPhase 3NCT02905266
A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma
A Phase 3 study testing Nivolumab and Ipilimumab in people with Melanoma, run by Bristol-Myers Squibb at 16 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 27 Oct 2016to 25 Oct 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
France6 sites
Local Institution
Lyon, 69373
Hopital De La Timone
Marseille, 13385
Local Institution
Nantes, 44093
Hopital Saint Louis
Paris, 75475
Local Institution
Paris, 75679
Hopital Trousseau - Chru Tours
Tours, 37044
Italy4 sites
Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med
Genova, 16128
Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori
Meldola (FC), 47014
Istituto Europeo Di Oncologia
Milan, 20141
Azienda Ospedaliera Citta della Salute e della Scienza
Torino, 10137
Australia3 sites
Greenslopes Private Hospital
Greenslopes, Queensland
Cabrini Hospital
Malvern, Victoria
Melanoma Institute Australia
North Sydney, New South Wales
Spain3 sites
Local Institution
Barcelona, 08036
Local Institution
Madrid, 28007
Local Institution
Seville, 41071
About this study
Official title: 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.
- Conditions
- Melanoma
- Being tested
- Nivolumab, Ipilimumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
-Specified dose on specified days
IpilimumabBiological
-Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and Ipilimumab Concomitant Administration | Experimental | Followed by Nivolumab monotherapy Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Nivolumab and Ipilimumab Sequential Administration | Experimental | Followed by Nivolumab monotherapy Receives: Biological: Nivolumab; Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Secondary outcomes (10)
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Geometric Mean Trough Concentration of Nivolumab
Measured: 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.
Measured: 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.
Measured: From the date of randomization to the first date of documented progression (approximately 26 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study start27 Oct 2016
- Primary completion23 Oct 2017
- Study completion25 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02905266
- Sponsor's protocol ID
- CA209-742
- Other IDs
- 2016-001941-26, 2016
- Status last verified
- Nov 2020
- First submitted
- 14 Sep 2016
- Last updated
- 17 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Menzies AM, Salman P, Frontera OA, Pook D, Hocking CM, Zakharia Y, Gurney H, Gedye C, Goh JC, Telivala B, Grob JJ, Lebbe C, de la Cruz Merino L, Machet L, Neidhardt EM, Qureshi A, Hosein F, Hamuro L, Simsek B, Amin A. Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800). Cancer. 2025 Jul 15;131(14):e35962. doi: 10.1002/cncr.35962.
PubMed 40614118
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIIb, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Previously Untreated Unresectable or Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02905266
- Acronym / sponsor ID
- CA209-742
- Conditions
- Melanoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 27 Oct 2016 (actual)
- Primary completion
- 23 Oct 2017 (actual)
- Study completion
- 25 Oct 2019 (actual)
- First posted
- 19 Sep 2016 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and Ipilimumab Concomitant Administration | Experimental | Biological: Nivolumab, Biological: IpilimumabFollowed by Nivolumab monotherapy |
| Nivolumab and Ipilimumab Sequential Administration | Experimental | Biological: Nivolumab, Biological: IpilimumabFollowed by Nivolumab monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab-Specified dose on specified days | Biological | Nivolumab and Ipilimumab Concomitant Administration, Nivolumab and Ipilimumab Sequential Administration |
| Ipilimumab-Specified dose on specified days | Biological | Nivolumab and Ipilimumab Concomitant Administration, Nivolumab and Ipilimumab Sequential Administration |
Primary outcome
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)
Time frame: 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.
10 secondary outcomes
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Geometric Mean Trough Concentration of Nivolumab
Time frame: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Objective Response Rate (ORR)
Time frame: 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)
Time frame: From the date of randomization to the first date of documented progression (approximately 26 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40614118Menzies AM, Salman P, Frontera OA, Pook D, Hocking CM, Zakharia Y, Gurney H, Gedye C, Goh JC, Telivala B, Grob JJ, Lebbe C, de la Cruz Merino L, Machet L, Neidhardt EM, Qureshi A, Hosein F, Hamuro L, Simsek B, Amin A. Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800). Cancer. 2025 Jul 15;131(14):e35962. doi: 10.1002/cncr.35962.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nivolumab and Ipilimumab in people with Melanoma, run by Bristol-Myers Squibb at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in France, Italy, Australia, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) (time frame: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02905266, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.