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Advanced CancerPhase 1/2NCT02658890

An Investigational Immuno-therapy Study of BMS-986205 Given in Combination With Nivolumab and in Combination With Both Nivolumab and Ipilimumab in Cancers That Are Advanced or Have Spread

A Phase 1/2 study testing BMS-986205, Nivolumab and Ipilimumab in people with Advanced Cancer and Melanoma, run by Bristol-Myers Squibb at 47 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of the study is to determine safety and effectiveness of experimental medication BMS-986205 when combined with Nivolumab and in combination with both Nivolumab and Ipilimumab in patients with cancers that are advanced or have spread. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
BMS-986205, Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
627 participants
Where
47 sitesin 11 countries
Study dates
14 Apr 2016to 26 Oct 2021
Phase
Phase 1/2
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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
  • During cohort expansion, subjects with advanced cancer that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
  • Subjects must have measurable disease
  • Subject must consent to provide previously collected tumor tissue and a tumor biopsy during screening.
  • At least 4 weeks since any previous treatment for cancer
  • Must be able to swallow pills or capsules
  • Eastern Cooperative Oncology Group(ECOG) Performance Status 0-1

Who cannot join

  • Active or chronic autoimmune diseases
  • Uncontrolled or significant cardiovascular disease
  • History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS)
  • Chronic hepatitis: Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
  • Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
  • Active infection
  • Other protocol defined inclusion/exclusion criteria could apply

Trial locations and contacts

47 sites in 11 countries.

47 sites in 11 countries

United States15 sites
  • Local Institution - 0005

    Atlanta, Georgia, 30322

  • Local Institution - 0048

    Atlanta, Georgia, 30342

  • Local Institution - 0027

    Chicago, Illinois, 60637

  • Local Institution - 0030

    Cleveland, Ohio, 44195

  • Local Institution - 0049

    Detroit, Michigan, 48201

  • Local Institution - 0033

    Hackensack, New Jersey, 07601

  • Local Institution - 0026

    La Jolla, California, 92093-0698

  • Local Institution - 0051

    Lutherville, Maryland, 21093

  • Local Institution - 0043

    Nashville, Tennessee, 37232

  • Local Institution - 0041

    New York, New York, 10016

  • Local Institution - 0034

    Philadelphia, Pennsylvania, 19111-2412

  • Local Institution - 0057

    Pittsburgh, Pennsylvania, 15232

  • Local Institution - 0006

    St Louis, Missouri, 63110

  • Local Institution - 0035

    Tampa, Florida, 33612-9497

  • Local Institution - 0028

    Tucson, Arizona, 85724-5024

Other trials in United States

Australia7 sites
  • Local Institution - 0044

    Brisbane, Queensland, 4102

  • Local Institution - 0008

    Clayton, Victoria, 3168

  • Local Institution - 0004

    Melbourne, Victoria, 3000

  • Local Institution - 0047

    Nedlands, Western Australia, 6009

  • Local Institution - 0045

    North Sydney, New South Wales, 2146

  • Local Institution - 0029

    Sydney, New South Wales, 2010

  • Local Institution - 0046

    Westmead, New South Wales, 2145

Other trials in Australia

France7 sites
  • Local Institution - 0040

    Lille, 59037

  • Local Institution - 0024

    Lyon, 69373

  • Local Institution - 0053

    Marseille, 13385

  • Local Institution - 0052

    Nantes, 44093

  • Local Institution - 0025

    Paris, 75005

  • Local Institution - 0023

    Toulouse, 31100

  • Local Institution - 0022

    Villejuif, 94800

Other trials in France

Canada5 sites
  • Local Institution - 0003

    Edmonton, Alberta, T6G 1Z2

  • Local Institution

    Greenfield Park, Quebec, J4V 2H1

  • Local Institution - 0036

    Montreal, Quebec, H3T 1E2

  • Local Institution - 0001

    Toronto, Ontario, M5G 1Z5

  • Local Institution - 0002

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Italy4 sites
  • Local Institution - 0010

    Milan, 20132

  • Local Institution - 0011

    Milan, 20133

  • Local Institution - 0012

    Milan, 20141

  • Local Institution - 0009

    Rozzano MI, 20089

Other trials in Italy

Spain3 sites
  • Local Institution - 0017

    Barcelona, 08035

  • Local Institution - 0016

    Madrid, 28040

  • Local Institution - 0018

    Madrid, 28050

Other trials in Spain

Germany2 sites
  • Local Institution - 0019

    Essen, 45147

  • Local Institution - 0013

    Heilbronn, 74078

Other trials in Germany

Finland1 site
  • Local Institution - 0059

    Helsinki, 00180

Other trials in Finland

Norway1 site
  • Local Institution - 0054

    Oslo, 0424

Other trials in Norway

Poland1 site
  • Local Institution - 0042

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

Sweden1 site
  • Local Institution - 0055

    Solna, 171 64

Other trials in Sweden

About this study

Official title: A Phase 1/2a Study of BMS-986205 Administered in Combination With Nivolumab (Anti-PD-1 Monoclonal Antibody) and in Combination With Both Nivolumab and Ipilimumab (Anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumors

The purpose of the study is to determine safety and effectiveness of experimental medication BMS-986205 when combined with Nivolumab and in combination with both Nivolumab and Ipilimumab in patients with cancers that are advanced or have spread. Pharmacokinetics and pharmacodynamics of BMS-986205 when combined with Nivolumab and in combination with Nivolumab and Ipilimumab in this patient population will also be assessed.

Being tested
BMS-986205, Nivolumab, Ipilimumab
Medical subject headings
Melanoma, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BMS-986205Drug

  • NivolumabDrug

    Also called BMS-936558, ANTI-PD1

  • IpilimumabDrug

    Also called BMS-734016, ANTI-CTLA-4

Study groups in NCT02658890
Study groupRoleWhat they receive
Combination Therapy (Dose Escalation)ExperimentalBMS 986205 + Nivolumab specified dose at specified intervals.
Receives: Drug: BMS-986205; Drug: Nivolumab
Combination Therapy (Dose Expansion)ExperimentalBMS 986205 + Nivolumab specified dose at specified intervals.
Receives: Drug: BMS-986205; Drug: Nivolumab
Combination Therapy 2 (Dose Expansion)ExperimentalBMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
Receives: Drug: BMS-986205; Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths

    Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation and deaths.

    Measured: From first dose to 100 days after last dose (up to 15 months)

  2. Number of Treated Participant With Laboratory Abnormalities - Thyroid

    The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study.

    Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Results reported in International System of Units (SI)

    Measured: From first dose to 100 days after last dose (up to 15 months)

  3. Number of Treated Participant With Laboratory Abnormalities - Liver

    The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study.

    Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Results reported in International System of Units (SI)

    Measured: From first dose to 100 days after last dose (up to 15 months)

  4. Number of Participants With a Best Overall Response (BOR) - Parts 2 and 3

    Best overall response (BOR) is defined as the best response designation over the study as a whole. Complete response (CR) or partial response (PR) determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. For those participants who have surgical resection, only pre-surgical tumor assessments will be considered in the determination of BOR. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease. (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)

  5. Percentage of Participants With an Objective Response Rate (ORR)- Parts 2 and 3

    Objective response rate (ORR) is defined as the percentage of all treated participants whose BOR is either a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

    Measured: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)

  6. Median Duration of Response (DoR) - Parts 2 and 3

    Duration of response (DoR) was computed for all treated subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

    Measured: From first dose to the date of disease progression, death, or until participants withdraw from the study, whichever occurs first (up to a maximum of 185 weeks)

  7. Progression Free Survival Rate (PFSR) at 24 Weeks - Parts 2 and 3

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 24 weeks. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 24 weeks after first dose

  8. Progression Free Survival Rate (PFSR) at 1 Year - Parts 2 and 3

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 1 year. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 1 year

  9. Progression Free Survival Rate (PFSR) at 2 Years - Parts 2 and 3

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 2 years. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 2 years

Secondary outcomes (16)
  1. Cmax

    Cmax is defined as the maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]

  2. Tmax

    Tmax is defined as the time of maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]

  3. AUC(TAU)

    AUC(TAU) is defined as the area under the concentration-time curve in 1 dosing interval. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose)

  4. Ctrough

    Ctrough is defined as the trough observed plasma concentration at the end of the dosing interval.

    Measured: At cycles 0 [up to 2 weeks] and at cycles 3, 5, 7, 10, 11, 13, 15 [each cycle is up to 4 weeks]

  5. CLT/F

    CLT/F is defined as the apparent total body clearance. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]

  6. Accumulation Index (AI) - AUC(TAU)

    Accumulation index (AI) of AUC(TAU) is calculated based on the ratio of AUC(TAU) at steady state to after the first dose. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose)

  7. Accumulation Index (AI) - Cmax

    Accumulation index (AI) of Cmax is calculated based on the ratio of Cmax at steady state to after the first dose. Pharmacokinetic parameters measured here are for BMS-986205.

    Measured: At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]

  8. Change From Baseline in Serum Kynurenine

    Pharmacodynamics assessed by change from baseline in serum kynurenine. Changes in kynurenine expression were evaluated in serum samples from participants treated using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Kynurenine is an important metabolite of the IDO-1 Enzyme. Change in Kynurenine levels from baseline is an important indicator of BMS-986205 (IDO1 inhibitor) pharmacodynamic activity.

    Measured: At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]

  9. Percent Change From Baseline in Serum Kynurenine

    Pharmacodynamics assessed by change from baseline in serum kynurenine. Changes in kynurenine expression were evaluated in serum samples from participants treated using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Kynurenine is an important metabolite of the IDO-1 Enzyme. Change in Kynurenine levels from baseline is an important indicator of BMS-986205 (IDO1 inhibitor) pharmacodynamic activity.

    Measured: At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]

  10. Number of Participants With a Best Overall Response (BOR) - Part 1 and Clinical Pharmacology Substudies

    Best overall response (BOR) is defined as the best response designation over the study as a whole. Complete response (CR) or partial response (PR) determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. For those participants who have surgical resection, only pre-surgical tumor assessments will be considered in the determination of BOR. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease. (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)

  11. Percentage of Participants With an Objective Response Rate (ORR) - Part 1 and Clinical Pharmacology Substudies

    Objective response rate (ORR) is defined as the percentage of all treated participants whose BOR is either a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. CR+PR confidence interval based on the Clopper and Pearson method.

    Measured: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)

  12. Median Duration of Response (DoR) - Part 1 and Clinical Pharmacology Substudies

    Duration of response (DoR) was computed for all treated subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

    Measured: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)

  13. Progression Free Survival Rate (PFSR) at 24 Weeks - Part 1 and Clinical Pharmacology Substudies

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 24 weeks. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 24 weeks after first dose

  14. Progression Free Survival Rate (PFSR) at 1 Year - Part 1 and Clinical Pharmacology Substudies

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 1 year. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 1 year

  15. Progression Free Survival Rate (PFSR) at 2 Years - Part 1 and Clinical Pharmacology Substudies

    Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 2 years. Reported values are estimates derived from Kaplan-Meier analyses.

    Measured: At 2 years

  16. Number of Participants With a Positive Anti-Drug Antibody (ADA) Test

    A participant with at least one ADA-positive sample relative to baseline after initiation of treatment with nivolumab or ipilimumab. ADA-Positive after initiation of treatment was defined as (1) an ADA detected (positive seroconversion) sample in a subject for whom ADA is not detected at baseline, or (2) an ADA detected sample with ADA titer to be at least 4-fold or greater (≥) than baseline positive titer.

    Measured: From first dose to last dose (up to approximately 48 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2016 (estimated)
  2. Study start14 Apr 2016
  3. Primary completion26 Oct 2021
  4. Study completion26 Oct 2021

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
627 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02658890
Sponsor's protocol ID
CA017-003
Other IDs
2015-004914-79, 2015
Status last verified
Aug 2023
First submitted
14 Jan 2016
Last updated
28 Aug 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BMS-986205, Nivolumab and Ipilimumab in people with Advanced Cancer and Melanoma, run by Bristol-Myers Squibb at 47 sites in 11 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 7 inclusion and 7 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 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, Australia, France, Canada, Italy and 6 more countries. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 28 Aug 2023). 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?

Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths (time frame: From first dose to 100 days after last dose (up to 15 months)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 28 Aug 2023.

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