First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors

Phase 1/2a First-In-Human Study of BMS-986218 Monoclonal Antibody Alone and in Combination With Nivolumab in Advanced Solid Tumors

The purpose of this study is to determine whether BMS-986218 both by itself and in combination with Nivolumab is safe and tolerable in the treatment of advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Advanced Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Biological: BMS-986218

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina, 1426
      • Local Institution - 0042
  • Ciudad Autónoma De Buenos Aires
    • ABB, Ciudad Autónoma De Buenos Aires, Argentina, C1199ABB
      • Local Institution - 0053
    • Caba, Ciudad Autónoma De Buenos Aires, Argentina, C1430EGF
      • Local Institution - 0057
  • Cordoba
    • Córdoba, Cordoba, Argentina, X5000FHP
      • Local Institution - 0062
    • Rio Cuarto, Cordoba, Argentina
      • Local Institution - 0060
    • Villa Siburu, Cordoba, Argentina, 5003
      • Local Institution - 0047
  • Distrito Federal
    • Buenos Aires, Distrito Federal, Argentina, 1121
      • Local Institution - 0059
• Australia
  • New South Wales
    • Northmead, New South Wales, Australia, 2152
      • Local Institution - 0026
    • Wollstonecraft, New South Wales, Australia, 2065
      • Local Institution - 0006
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 0049
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0039
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0037
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution - 0023
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0027
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0022
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8420383
      • Local Institution - 0041
    • Santiago, Metropolitana, Chile, 7710007
      • Local Institution - 0048
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2520598
      • Local Institution - 0052
• Finland
  • Helsinki, Finland, 00029
    • Local Institution - 0045
• France
  • Lyon Cedex 08, France, 69373
    • Local Institution - 0019
  • Toulouse Cedex 9, France, 31059
    • Local Institution - 0020
  • Villejuif, France, 94800
    • Local Institution - 0018
• Germany
  • Dresden, Germany, 01307
    • Local Institution - 0009
  • Essen, Germany, 45147
    • Local Institution - 0030
• Israel
  • Haifa, Israel, 3109601
    • Local Institution - 0029
  • Ramat Gan, Israel, 52621
    • Local Institution - 0008
• Italy
  • Napoli, Italy, 80131
    • Local Institution - 0011
  • Rozzano, Italy, 20089
    • Local Institution - 0061
  • Siena, Italy, 53100
    • Local Institution - 0010
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0038
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 0043
• Norway
  • Oslo, Norway, 0379
    • Local Institution - 0040
• Poland
  • Warszawa, Poland, 02-781
    • Local Institution - 0036
• Romania
  • Cluj Napoca, Romania, 400015
    • Local Institution - 0034
  • Craiova, Romania, 200347
    • Local Institution - 0035
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0014
  • Madrid, Spain, 28007
    • Local Institution - 0056
  • Madrid, Spain, 28040
    • Local Institution - 0055
  • Madrid, Spain, 28050
    • Local Institution - 0013
  • Malaga, Spain, 29010
    • Local Institution - 0054
  • Pamplona, Spain, 31008
    • Local Institution - 0012
• Switzerland
  • Lausanne, Switzerland, 1011
    • Local Institution - 0017
  • Zuerich, Switzerland, 8091
    • Local Institution - 0031
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0058
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0025
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0002
    • New Brunswick, New Jersey, United States, 08009
      • Local Institution - 0028
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0007
    • New York, New York, United States, 10032
      • Local Institution - 0001
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • Local Institution - 0015
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0004
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Local Institution - 0033

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Inclusion Criteria:

• Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists
• Advanced stage cutaneous melanoma who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-programmed cell death 1 (anti-PD-1) or anti-programmed death ligand 1 (anti-PD-L1) (For Part 2A)
• Non-small cell lung cancer (NSCLC) (adenocarcinoma or squamous cell carcinoma) who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-PD-1 or anti-PD-L1 (For Parts 2B & 2C)
• Microsatellite Stable Colorectal Cancer (MSS CRC) who have received standard therapies with proven survival benefit (Part 2D)

Exclusion Criteria:

• Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded
• Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy
• Prior anti-cancer treatments such as chemotherapy, radiotherapy, hormonal, or immunotherapy (including anti-PD-1/PD-L1) are permitted

Other protocol-defined inclusion/exclusion criteria 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A: Monotherapy (BMS-986218)	Biological: BMS-986218; Specified dose on specified days
Experimental: Part 1B: Combination Therapy (BMS-986218 + Nivolumab)	Biological: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Biological: BMS-986218; Specified dose on specified days
Experimental: Part 2A: Monotherapy (BMS-986218 OR Ipilimumab)	Biological: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Biological: BMS-986218; Specified dose on specified days
Experimental: Part 2B: Monotherapy (BMS-986218)	Biological: BMS-986218; Specified dose on specified days
Experimental: Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab)	Biological: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Biological: BMS-986218; Specified dose on specified days
Experimental: Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)	Biological: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Biological: BMS-986218; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.	From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
Number of Participants With Serious Adverse Events (SAEs)	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
Number of Participants With Adverse Events (AEs) Meeting Protocol-defined Dose-limiting Toxicity (DLT) Criteria	Dose-Limiting Toxicities (DLTs) are effects of a treatment that are serious enough to prevent an increase in dose of that treatment. Grade 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death Gastrointestinal DLT: Grade 2 colitis >5 days; Grade ≥3 diarrhea/colitis Hepatic DLT: Grade 4 serum transaminases (AST & ALT), alkaline phosphatase (ALP), or total bilirubin elevations; Grade 3 serum AST, ALT, or ALP elevations lasting >5 days or with clinical symptoms or bilirubin > 2×ULN without cholestasis Hematologic DLT: Grade 4 neutropenia ≥7 days; Grade 4 thrombocytopenia Dermatologic DLT: Grade 4 rash; Grade 3 rash if no improvement after 1-2-week infusion delay Other DLTs: Grade 2 drug-related uveitis, episcleritis, iritis, eye pain, or blurred vision that doesn't respond to treatment, doesn't improve within the re-treatment period OR requires systemic treatment; Grade 3 drug-related uveitis, episcleritis, iritis, pneumonitis, bronchospasm, or neurologic toxicity	From first dose of study medication through 60 days following last dose of study treatment (assessed for an average of 7 months up to a max of approximately 27 months)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.	From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
Number of Participants Who Died	Number of participants who died during the study	From randomization (Part 2A and 2B) or first dose (Part 1, 2C and 2D) until study closure (Up to approximately 83 months)
Objective Response Rate (ORR) for Part 2 Only	Objective response rate (ORR) is defined as the percent of all treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression).	From the start of the study treatment until disease progression, or the last response recorded, taking into account any requirement for confirmation and censoring rules regarding subsequent therapy (Up to approximately 83 months)
Median Duration of Response (mDOR) for Part 2 Only	Duration of response (DOR) for a participant with a BOR of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1 or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression). Based on Kaplan-Meier estimates of duration of response	From the date of first dose to the date of the first objectively documented tumor progression, or death, whichever occurs first (Up to approximately 83 months)
Progression-free Survival Rate (PFSR) at 24, 36, and 48 Weeks for Part 2 Only	Progression-free survival (PFS) for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Based on Kaplan-Meier estimates of progression-free survival rate Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression).	At 24, 36, and 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) for Part1A and Part1B Only	Objective response rate (ORR) is defined as the percent of all treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression).	From the start of the study treatment until disease progression, or the last response recorded, taking into account any requirement for confirmation and censoring rules regarding subsequent therapy (Up to approximately 83 months)
Median Duration of Response (mDOR) for Part1A and Part1B Only	Duration of response (DOR) for a participant with a BOR of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1 or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression). Based on Kaplan-Meier estimates of duration of response	From the date of first dose to the date of the first objectively documented tumor progression, or death, whichever occurs first (Up to approximately 83 months)
Progression-free Survival Rate (PFSR) at 24, 36, and 48 Weeks for Part1A and Part1B Only	Progression-free survival (PFS) for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression). Based on Kaplan-Meier estimates of progression-free survival rate	At 24, 36, and 48 weeks
Maximum Observed Serum Concentration (Cmax) for BMS-986218	Cmax is the maximum observed serum concentration for BMS-986218.	On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] for BMS-986218	Tmax is the time taken to reach the maximum observed serum concentration (Cmax) for BMS-986218.	On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] for BMS-986218	AUC (TAU) is the area measured under the concentration-time curve taken over the dosing interval for BMS-986218.	On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
Observed Concentration at the End of a Dosing Interval (Ctau) for BMS-986218	Ctau is the observed serum concentration at the end of the dosing interval for BMS-986218.	On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
Total Body Clearance (CLT/F) for BMS-986218		At Cycle 3 Day 1 (Each Cycle is of 28 Days)
Average Concentration Over a Dosing Interval (AUC[TAU]/Tau) at Steady State (Css-avg) for BMS-986218		At Cycle 3 Day 1 (Each Cycle is of 28 Days)
Ratio of an Exposure Measure at Steady State to That After the First Dose (Exposure Measure Includes Cmax) (AI_Cmax) for BMS-986218		At Cycle 3 Day 1 (Each Cycle is of 28 Days)
Accumulation Index Ratio of AUC at Steady State to That After the First Dose (AI_AUC) for BMS-986218		At Cycle 3 Day 1 (Each Cycle is of 28 Days)
Terminal Serum Half-life (T-HALF) for BMS-986218		At Cycle 3 Day 1 (Each Cycle is of 28 Days)
Time of Maximum Observed Concentration (Tmax) for BMS-986218	Tmax is the time taken to reach the maximum observed serum concentration (Cmax) for BMS-986218.	On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
Trough Observed Plasma Concentration (Ctrough) for BMS-986218	Ctrough is the lowest observed serum concentration for BMS-986218.	At Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1 (Each Cycle is of 28 Days)
Number of Participants With Anti-drug Antibodies (ADA) to BMS-986218	Baseline ADA Positive: Participant with baseline ADA-positive sample ADA Positive: Participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment Persistent Positive (PP): ADA-positive sample at 2 or more consecutive timepoints, where the first and last ADA-positive samples are at least 16weeks apart Not PP-Last Sample Positive: Not persistent but with ADA-positive sample at the last sampling timepoint Other Positive: Not persistent but some ADA-positive samples with the last sample being negative ADA Negative: Participant with no ADA-positive sample after initiation of treatment	From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2017
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: April 7, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Nivolumab; Ipilimumab; BMS-986218
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA022-001; 2017-000597-11 (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