An Investigational Immunotherapy Study of BMS-986258 Alone and in Combination With Nivolumab in Participants With Solid Cancers That Are Advanced or Have Spread

Phase 1

Terminated

Conditions: Advanced Cancer

Interventions: Biological: BMS-986258
Biological: Nivolumab
Drug: rHuPH20

Registration Number: NCT03446040

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this study is to determine whether BMS-986258 both monotherapy and in combination with Nivolumab is safe and tolerable in the treatment of advanced malignant tumors.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 92

Inclusion Criteria

Histologic confirmation of one of the 5 tumors [renal cell carcinoma (RCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC)] (metastatic, recurrent, and/or unresectable), with measurable disease per response evaluation criteria in solid tumors v1.1 (RECIST v1.1)
Eastern Cooperative Oncology Group Performance Status of 0 or 1
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Women must agree to follow specific methods of contraception, if applicable

Exclusion Criteria

Active, known or suspected autoimmune disease
Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy
Other active malignancy requiring concurrent intervention

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part B Dose Escalation: BMS-986258 + nivolumab	Nivolumab	-
Part C Cohort Expansion: BMS-986258 + nivolumab	BMS-986258	-
Part A1: BMS-986258 + Recombinant human hyaluronidase PH20 (rHuPH20)	BMS-986258	-
Part A Dose Escalation: BMS-986258	BMS-986258	-
Part A1: BMS-986258 + Recombinant human hyaluronidase PH20 (rHuPH20)	rHuPH20	-
Part C Cohort Expansion: BMS-986258 + nivolumab	Nivolumab	-
Part B Dose Escalation: BMS-986258 + nivolumab	BMS-986258	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks)	An Adverse Event (AE) is any new untoward medical occurrence or worsening of a preexisting medical condition in a study participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can 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. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose: * Results in death * Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event) * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect.
Number of Participants Who Died During the Study	From first dose until death due to any cause (up to approximately 78 months)	The number of participants who died during the study.
Number of Participants With Dose Limiting Toxicities (DLTs)	From first dose (Cycle 1 Day 1) until day 28 (Cycle 1 Day 28)	Dose-limiting toxicity (DLT) refers to a side effect or adverse reaction caused by a drug that is severe enough to prevent an increase in dose or level of that drug. It is typically identified during clinical trials to determine the highest dose of a drug that can be given safely without causing unacceptable side effects. A participant was considered DLT evaluable if they received 1 dose of BMS-986258 in Part A or 1 dose of BMS-986258 and nivolumab 480mg in Part B and completed the DLT observation period. Participants who withdraw from the study during the 4-week DLT evaluation period for reasons other than a DLT may be replaced with a new participant at the same dose level.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	From first dose until disease progression or death, whichever occurred first (up to approximately 78 months)	Objective response rate (ORR) is defined as the percent of treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Median Duration of Response (mDOR)	From first dose until disease progression or death whichever occurred first (up to approximately 78 months)	Median duration of response (mDOR) for a participant with a best overall response (BOR) of complete response (CR) or partial response (PR) is defined as the time between the date of first response and the date of the first objectively documented disease progression (DP) per RECIST v1.1 or death, whichever occurred first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. Based on Kaplan-Meier estimates.
Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months	At 6, 9, and 12 months after first dose	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 occurred first. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions.
Maximum Plasma Concentration (Cmax) of BMS-986258	Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)	Cmax (Maximum Concentration) is the highest level of a drug in the blood after it has been taken. It shows the peak level of the drug, which helps in understanding how much of the drug is absorbed and how strong its effects might be.
Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258	Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)	AUC (0-T) is the total exposure to the drug over a specific period; from the time you take it until a specified time. It helps in understanding the overall amount of drug that has been in your body over that time period.
Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258	Part A and B: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)	AUC(TAU) (Area Under the Curve over the Dosing Interval) is the total exposure to the drug over one complete dosing interval (the time between doses). It helps in understanding how much of the drug is in your body over the entire period between doses, which is important for determining the right dosing schedule.
Concentration at the End of the Dosing Interval (Ctau) of BMS-986258	Part A and B: On Cycle 1 Day 29 and Cycle 3 Day 29 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 29 and Cycle 2 Day 1 predose (1 cycle = 8 weeks)	Ctau (Concentration at the End of the Dosing Interval) is the level of the drug in the blood just before the next dose is due. It shows how much of the drug remains in your body before taking the next dose, which helps in ensuring that the drug levels stay effective without dropping too low.
Time to Reach Maximum Concentration (Tmax) of BMS-986258	Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)	Tmax (Time to Reach Maximum Concentration) is the time it takes for the drug to reach its highest level in the blood after taking it. It helps in understanding how quickly the drug starts to work and reaches its peak effect.
Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab	From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks)	Baseline ADA-positive participant is defined as a participant who has an ADA-detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment

Trial Locations

Locations (16): Local Institution - 0004
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Los Angeles, California, United States
Local Institution - 0006
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Los Angeles, California, United States
Local Institution - 0007
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Aurora, Colorado, United States
University Of Iowa Hospitals And Clinics
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Iowa City, Iowa, United States
Local Institution - 0018
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Ann Arbor, Michigan, United States
Local Institution - 0010
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Grand Rapids, Michigan, United States
Local Institution - 0012
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Lebanon, New Hampshire, United States
Local Institution - 0016
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Cincinnati, Ohio, United States
Local Institution - 0005
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Pittsburgh, Pennsylvania, United States
Local Institution - 0002
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Germantown, Tennessee, United States
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Local Institution - 0004
🇺🇸Los Angeles, California, United States