A Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab or docetaxel in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.

Official Title
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A Phase 1/2 Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors

Conditions
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Cervical Cancer, Gastric/Gastroesophageal Junction Adenocarcinoma, Microsatellite Stable Colorectal Cancer, Non-Small-Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell, Urothelial Carcinoma, Pancreatic Adenocarcinoma, Melanoma, Ovarian Neoplasms, Triple Negative Breast Neoplasms

Intervention / Treatment
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* Drug: BMS-986340
* Drug: BMS-936558-01
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable. Eastern Cooperative Oncology Group Performance Status of 0 or 1 Radiographically documented progressive disease on or after the most recent therapy Received standard-of-care therapies, (except for Part 1C, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant Exclusion Criteria: Women who are pregnant or breastfeeding Primary central nervous system (CNS) malignancy Untreated CNS metastases Leptomeningeal metastases Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment Active, known, or suspected autoimmune disease Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment Prior organ or tissue allograft Uncontrolled or significant cardiovascular disease Major surgery within 4 weeks of study drug administration History of or with active interstitial lung disease or pulmonary fibrosis Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A: BMS-986340 Dose Escalation<br> | Drug: BMS-986340<br>* Specified dose on specified days<br>|
| Experimental: Part 2A: BMS-986340 Dose Expansion<br> | Drug: BMS-986340<br>* Specified dose on specified days<br>|
| Experimental: Part 1B: BMS-986340 + Nivolumab Dose Escalation<br> | Drug: BMS-986340<br>* Specified dose on specified days<br>Drug: BMS-936558-01<br>* Specified dose on specified days<br>* Other names: Nivolumab;|
| Experimental: Part 2B: BMS-986340 + Nivolumab Dose Expansion<br> | Drug: BMS-986340<br>* Specified dose on specified days<br>Drug: BMS-936558-01<br>* Specified dose on specified days<br>* Other names: Nivolumab;|
| Experimental: Part 1C: BMS-986340 + Docetaxel Dose Escalation<br> | Drug: BMS-986340<br>* Specified dose on specified days<br>Drug: Docetaxel<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 120 weeks | 
| Incidence of serious adverse events (SAEs) |  | Up to 120 weeks | 
| Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria |  | Up to 120 weeks | 
| Incidence of AEs leading to discontinuation |  | Up to 120 weeks | 
| Incidence of AEs leading to death |  | Up to 120 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) parameters of BMS-986340 administered as monotherapy: Maximum concentration (Cmax) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered as monotherapy: Time to maximum concentration (Tmax) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered as monotherapy: Area under the concentration-time curve 1 dosing interval (AUC (TAU)) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered as monotherapy: Observed concentration at the end of the dosing interval (Ctau) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with nivolumab: Maximum concentration (Cmax) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with docetaxel: Cmax |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with nivolumab: Time to maximum concentration (Tmax) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with docetaxel: Tmax |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with nivolumab: Area under the concentration-time curve in 1 dosing interval (AUC(TAU)) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with docetaxel: AUC(TAU) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with nivolumab: Observed concentration at the end of the dosing interval (Ctau) |  | Up to 120 weeks | 
| PK parameters of BMS-986340 administered in combination with docetaxel: Ctau |  | Up to 120 weeks | 
| Incidence of anti-drug antibodies to BMS- 986340 when administered as monotherapy |  | Up to 120 weeks | 
| Incidence of anti-drug antibodies to BMS- 986340 when administered in combination with nivolumab |  | Up to 120 weeks | 
| Incidence of anti-drug antibodies to BMS- 986340 when administered in combination with docetaxel |  | Up to 120 weeks | 
| Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator |  | At 6 months, 12 months | 
| Disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator |  | At 6 months, 12 months | 
| Duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator |  | At 6 months, 12 months | 
| Progression-free survival rate (PFSR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator |  | At 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, BMS-986340, Cervical Cancer, First-in-human, GEJ, Gastric/Gastroesophageal Junction Adenocarcinoma, HNSCC, Microsatellite Stable Colorectal Cancer, MSS CRC, Nivolumab, Non-Small-Cell Lung Cancer, NSCLC, SCCHN, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell, Urothelial Carcinoma, Pancreatic Adenocarcinoma, Melanoma, Ovarian Neoplasms, Triple Negative Breast Neoplasms