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

NCT03110107 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA022-0012017-000597-11
• Study Type: interventional
• Target: 376
• Locations: 17 countries
• Sites: 52

Brief Summary

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.

Conditions

Advanced Cancer

Keywords

BMS-986218; Nivolumab; Ipilimumab

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (15)

• Objective Response Rate (ORR) for Part1A and Part1B Only

  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

  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

  At 24, 36, and 48 weeks

• 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 From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] 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)

Study Arms (6)

Part 1A: Monotherapy (BMS-986218)

EXPERIMENTAL

Biological: BMS-986218

Part 1B: Combination Therapy (BMS-986218 + Nivolumab)

EXPERIMENTAL

Biological: BMS-986218; Biological: Nivolumab

Part 2A: Monotherapy (BMS-986218 OR Ipilimumab)

EXPERIMENTAL

Biological: Ipilimumab; Biological: BMS-986218

Part 2B: Monotherapy (BMS-986218)

EXPERIMENTAL

Biological: BMS-986218

Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab)

EXPERIMENTAL

Biological: BMS-986218; Biological: Nivolumab

Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)

EXPERIMENTAL

Biological: BMS-986218; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: Yervoy

Part 2A: Monotherapy (BMS-986218 OR Ipilimumab)

BMS-986218 BIOLOGICAL

Specified dose on specified days

Part 1A: Monotherapy (BMS-986218); Part 1B: Combination Therapy (BMS-986218 + Nivolumab); Part 2A: Monotherapy (BMS-986218 OR Ipilimumab); Part 2B: Monotherapy (BMS-986218); Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab); Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo

Part 1B: Combination Therapy (BMS-986218 + Nivolumab); Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab); Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (52)

Local Institution - 0058

Atlanta, Georgia, 30342, United States

Location

Local Institution - 0025

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0002

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0028

New Brunswick, New Jersey, 08009, United States

Location

Local Institution - 0001

New York, New York, 10032, United States

Location

Local Institution - 0007

New York, New York, 10065, United States

Location

Local Institution - 0015

Monroeville, Pennsylvania, 15146, United States

Location

Local Institution - 0004

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0033

Sioux Falls, South Dakota, 57104, United States

Location

Local Institution - 0042

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1426, Argentina

Location

Local Institution - 0053

ABB, Buenos Aires F.D., C1199ABB, Argentina

Location

Local Institution - 0057

CABA, Buenos Aires F.D., C1430EGF, Argentina

Location

Local Institution - 0062

Córdoba, Córdoba Province, X5000FHP, Argentina

Location

Local Institution - 0060

Río Cuarto, Córdoba Province, 0, Argentina

Location

Local Institution - 0047

Villa Siburu, Córdoba Province, 5003, Argentina

Location

Local Institution - 0059

Buenos Aires, Distrito Federal, 1121, Argentina

Location

Local Institution - 0026

Northmead, New South Wales, 2152, Australia

Location

Local Institution - 0006

Wollstonecraft, New South Wales, 2065, Australia

Location

Local Institution - 0049

Murdoch, Western Australia, 6150, Australia

Location

Local Institution - 0039

Ghent, 9000, Belgium

Location

Local Institution - 0037

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0023

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0027

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution - 0022

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0052

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Local Institution - 0048

Santiago, Santiago Metropolitan, 7710007, Chile

Location

Local Institution - 0041

Santiago, Santiago Metropolitan, 8420383, Chile

Location

Local Institution - 0045

Helsinki, 00029, Finland

Location

Local Institution - 0019

Lyon, 69373, France

Location

Local Institution - 0020

Toulouse, 31059, France

Location

Local Institution - 0018

Villejuif, 94800, France

Location

Local Institution - 0009

Dresden, 01307, Germany

Location

Local Institution - 0030

Essen, 45147, Germany

Location

Local Institution - 0029

Haifa, 3109601, Israel

Location

Local Institution - 0008

Ramat Gan, 52621, Israel

Location

Local Institution - 0011

Napoli, 80131, Italy

Location

Local Institution - 0061

Rozzano, 20089, Italy

Location

Local Institution - 0010

Siena, 53100, Italy

Location

Local Institution - 0038

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0043

Nijmegen, 6525 GA, Netherlands

Location

Local Institution - 0040

Oslo, 0379, Norway

Location

Local Institution - 0036

Warsaw, 02-781, Poland

Location

Local Institution - 0034

Cluj-Napoca, 400015, Romania

Location

Local Institution - 0035

Craiova, 200347, Romania

Location

Local Institution - 0014

Barcelona, 08035, Spain

Location

Local Institution - 0056

Madrid, 28007, Spain

Location

Local Institution - 0055

Madrid, 28040, Spain

Location

Local Institution - 0013

Madrid, 28050, Spain

Location

Local Institution - 0054

Málaga, 29010, Spain

Location

Local Institution - 0012

Pamplona, 31008, Spain

Location

Local Institution - 0017

Lausanne, 1011, Switzerland

Location

Local Institution - 0031

Zurich, 8091, Switzerland

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

Ipilimumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2017
• First Posted: April 12, 2017
• Study Start: May 4, 2017
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Locations

CL (3); RO (2); BE (1); US (9); CH (2); FI (1); AR (7); NL (2); DE (2); CA (4); FR (3); AU (3); ES (6); PL (1); NO (1); IL (2); IT (3)