A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of nivolumab when given under the skin with or without rHuPH20. This study will include participants with 1 of the following advanced or metastatic tumors approved for treatment with nivolumab monotherapy: non-small cell lung cancer (NSCLC) renal cell carcinoma (RCC) unresectable or metastatic melanoma hepatocellular carcinoma (HCC) microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC) in Part B, other solid tumors may be considered at the discretion of the Clinical Trial Physician In addition to the above tumors, Part E will also include participants with metastatic urothelial carcinoma (mUC).

Official Title
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Phase I/II Pharmacokinetic Multi-Tumor Study of Subcutaneous Formulation of Nivolumab Monotherapy

Conditions
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Neoplasms by Site

Intervention / Treatment
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* Biological: nivolumab
* Drug: rHuPH20
* Biological: nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types: Metastatic squamous or non-squamous NSCLC RCC, advanced or metastatic Melanoma HCC CRC, metastatic (MSI-H or dMMR) In Part B, other solid tumor types may be considered at the discretion of the Medical Monitor In Part E, Metastatic urothelial carcinoma Measurable disease as per RECIST version 1.1 criteria ECOG performance status of 0 or 1 Exclusion Criteria: Active brain metastases or leptomeningeal metastases Ocular melanoma Active, known, or suspected autoimmune disease 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Group 1: nivolumab (dose 1) + rHuPH20<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Drug: rHuPH20<br>* Specified dose on specified days Permeation enhancer<br>* Other names: ENHANZE™ DP;Biological: nivolumab<br>* (IV) Specified Dose on Specified Days<br>* Other names: BMS-936558;|
| Experimental: Part B, Group 3: nivolumab (dose 2) + rHuPH20<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Drug: rHuPH20<br>* Specified dose on specified days Permeation enhancer<br>* Other names: ENHANZE™ DP;Biological: nivolumab<br>* (IV) Specified Dose on Specified Days<br>* Other names: BMS-936558;|
| Experimental: Part B, Group 2: nivolumab (dose 1)<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Biological: nivolumab<br>* (IV) Specified Dose on Specified Days<br>* Other names: BMS-936558;|
| Experimental: Part B, Group 4: nivolumab (dose 2)<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Biological: nivolumab<br>* (IV) Specified Dose on Specified Days<br>* Other names: BMS-936558;|
| Experimental: Part C: nivolumab (dose 3) + rHuPH20<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Drug: rHuPH20<br>* Specified dose on specified days Permeation enhancer<br>* Other names: ENHANZE™ DP;|
| Experimental: Part D, Group 5: nivolumab (dose 3) + rHuPH20<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Drug: rHuPH20<br>* Specified dose on specified days Permeation enhancer<br>* Other names: ENHANZE™ DP;|
| Experimental: Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20<br> | Biological: nivolumab<br>* (Subcutaneous) Specified dose on specified days<br>* Other names: BMS-986298;Drug: rHuPH20<br>* Specified dose on specified days Permeation enhancer<br>* Other names: ENHANZE™ DP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) |  | Approximately 4 years | 
| Time of maximum observed serum concentration (Tmax) |  | Approximately 4 years | 
| Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)] |  | Approximately 4 years | 
| Observed serum concentration at the end of a dosing interval (Ctau) |  | Approximately 4 years | 
| Trough observed serum nivolumab concentration (Ctrough) |  | Approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | Approximately 4 years | 
| Incidence of AEs leading to deaths |  | Approximately 4 years | 
| Incidence of AEs leading to laboratory abnormalities |  | Approximately 4 years | 
| Incidence of AEs leading to discontinuation |  | Approximately 4 years | 
| Incidence of Treatment Related AEs (TRAEs) |  | Approximately 4 years | 
| Incidence of TRAEs leading to laboratory abnormalities |  | Approximately 4 years | 
| Incidence of TRAEs leading to discontinuation |  | Approximately 4 years | 
| Incidence of TRAEs leading to deaths |  | Approximately 4 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Approximately 4 years | 
| Incidence of Treatment Related SAEs (TRSAEs) |  | Approximately 4 years | 
| Incidence of death |  | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory values: Hematology tests |  | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory values: Chemistry tests |  | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory values: Serology tests |  | Approximately 4 years | 
| Number of Clinically Significant Changes in Lab Assessment of: Blood Serum |  | Approximately 4 years | 
| Number of Clinically Significant Changes in Lab Assessment of: Urine |  | Approximately 4 years | 
| Incidence of AEs in the broad standardized MedDRA queries (SMQ) of Anaphylactic Reaction |  | Approximately 4 years | 
| Incidence of events within the hypersensitivity/infusion reaction select AE category |  | Approximately 4 years | 
| Incidence of anti-nivolumab antibodies |  | Approximately 4 years | 
| Incidence of neutralizing antibodies |  | Approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rHuPH20, Subcutaneous, Nivolumab