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

• ClinicalTrials.gov Identifier: NCT03110107
• Recruitment Status: Terminated
• First Posted: April 12, 2017
• Last Update Posted: May 3, 2024
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: April 7, 2017
• First Posted Date: April 12, 2017
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: May 4, 2017
• Actual Primary Completion Date: April 4, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 17, 2021)

• Incidence of Adverse Events (AEs) [ Time Frame: Up to 2 years ]
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 2 years ]
• Incidence of AEs meeting protocol- defined dose-limiting toxicity (DLT) criteria [ Time Frame: Up to 2 years ]
• Incidence of AEs leading to discontinuation [ Time Frame: Up to 2 years ]
• Incidence of death [ Time Frame: Up to 2 years ]
• Objective Response Rate (ORR) [ Time Frame: Up to 4 years ]
  Parts 2A, 2B, 2C and 2D
• Median Duration of Response (mDOR) [ Time Frame: Up to 4 years ]
  Parts 2A, 2B, 2C and 2D
• Progression Free Survival Rate (PFSR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 4 years ]
  Parts 2A, 2B, 2C and 2D

Original Primary Outcome Measures (submitted: April 7, 2017)

• Incidence of Adverse Events (AEs) [ Time Frame: Up to 3 years ]
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 3 years ]
• Objective Response Rate (ORR) of BMS-986218 monotherapy relative to Ipilimumab in immuno-oncology (IO) progressed melanoma cohort [ Time Frame: Up to 3 years ]
• Median Duration of Response (mDOR) of BMS-986218 monotherapy relative to Ipilimumab in IO progressed melanoma cohort [ Time Frame: Up to 3 years ]
• Progression Free Survival (PFS) of BMS-986218 monotherapy relative to Ipilimumab in IO progressed melanoma cohort [ Time Frame: Up to 3 years ]

Current Secondary Outcome Measures (submitted: November 17, 2021)

• ORR [ Time Frame: Up to 4 years ]
  Parts 1A and 1B
• mDOR [ Time Frame: Up to 4 years ]
  Parts 1A and 1B
• PFSR by RECIST v1.1 [ Time Frame: Up to 4 years ]
  Parts 1A and 1B
• Incidence of anti-drug antibody (ADA) [ Time Frame: Up to 4 years ]
• Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 4 years ]
• Time of maximum observed plasma concentration (Tmax) [ Time Frame: Up to 4 years ]
• Trough observed serum concentration (Ctrough) [ Time Frame: Up to 4 years ]

Original Secondary Outcome Measures (submitted: April 7, 2017)

• ORR of BMS-986218 alone or in combination with Nivolumab [ Time Frame: Up to 3 years ]
• mDOR of BMS-986218 alone or in combination with Nivolumab [ Time Frame: Up to 3 years ]
• PFS of BMS-986218 alone or in combination with Nivolumab [ Time Frame: Up to 3 years ]
• Incidence of anti-drug antibody to BMS-986218 [ Time Frame: Up to 3 years ]
• Percentange of change from baseline in T-regulatory cells (Tregs) [ Time Frame: Up to 3 years ]
• Maximum observed serum concentration (Cmax) [ Time Frame: Up to 3 years ]
• Time of maximum observed concentration (Tmax) [ Time Frame: Up to 3 years ]
• Area under the concentration-time curve [ Time Frame: Up to 3 years ]
  Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)]
• Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] [ Time Frame: Up to 3 years ]
• Trough observed serum concentration (Ctrough) [ Time Frame: Up to 3 years ]
• Total body clearance (CLT) [ Time Frame: Up to 3 years ]
• Average serum concentration over a dosing interval (AUC[TAU]/tau) at steady state (Css-avg) [ Time Frame: Up to 3 years ]
• Ratio of an exposure measure at steady state to that after the first dose [exposure measure includes AUC[TAU] and Cmax (AI)] [ Time Frame: Up to 3 years ]
• Terminal serum half-life if data permit (T-HALF) [ Time Frame: Up to 3 years ]
• Observed concentration at the end of a dosing interval (Ctau) [ Time Frame: Up to 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors
• Official Title: Phase 1/2a First-In-Human Study of BMS-986218 Monoclonal Antibody Alone and in Combination With Nivolumab in Advanced Solid Tumors
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cancer

Intervention

• Biological: Ipilimumab
  Specified dose on specified days
  Other Name: Yervoy
• Biological: BMS-986218
  Specified dose on specified days
• Biological: Nivolumab
  Specified dose on specified days
  Other Name: Opdivo

Study Arms

• Experimental: Part 1A: Monotherapy (BMS-986218)
  Intervention: Biological: BMS-986218
• Experimental: Part 1B: Combination Therapy (BMS-986218 + Nivolumab)
  Interventions:

  • Biological: BMS-986218
  • Biological: Nivolumab
• Experimental: Part 2A: Monotherapy (BMS-986218 OR Ipilimumab)
  Interventions:

  • Biological: Ipilimumab
  • Biological: BMS-986218
• Experimental: Part 2B: Monotherapy (BMS-986218)
  Intervention: Biological: BMS-986218
• Experimental: Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab)
  Interventions:

  • Biological: BMS-986218
  • Biological: Nivolumab
• Experimental: Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)
  Interventions:

  • Biological: BMS-986218
  • Biological: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 2, 2024): 512
• Original Estimated Enrollment (submitted: April 7, 2017): 531
• Actual Study Completion Date: April 4, 2024
• Actual Primary Completion Date: April 4, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Canada, Chile, Finland, France, Germany, Israel, Italy, Netherlands, Norway, Poland, Romania, Spain, Switzerland, United States
• Removed Location Countries: Denmark

Administrative Information

• NCT Number: NCT03110107
• Other Study ID Numbers: CA022-001; 2017-000597-11 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: April 2024