A Study Evaluating the Drug Levels of Iplimumab Given Under the Skin Alone and in Combination With Nivolumab in Multiple Tumor Types

Study Overview
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Brief Summary
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A study evaluating the drug levels of ipilimumab alone and in combination with nivolumab applied under the skin in various tumor types

Official Title
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A Phase 1/2 Pharmacokinetic Multi-tumor Study of Subcutaneous Formulation of Ipilimumab Monotherapy and in Combination With Subcutaneous Nivolumab

Conditions
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Tumor

Intervention / Treatment
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* Drug: ipilimumab
* Drug: nivolumab
* Drug: ENHANZE (rHuPH20)
* Drug: nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Men and women must follow methods of contraception as described in the protocol Part 1 Arms A and B: Metastatic Melanoma - Previously untreated, histologically confirmed stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system v.8.0 Part 1 Arm A:Advanced/mUC - Participants with histologically or cytologically confirmed urothelial carcinoma. Part 1 Arm A: Advanced HCC Participants with histological confirmation of Hepatocellular Cancer (HCC) Part 2 Arm A: Metastatic NSCLC - Participants with histologically confirmed stage IV or recurrent Non Small Cell Lung Cancer (NSCLC) Part 2 Arm B: Advanced or Metastatic RCC Histological confirmation of Renal Cell Carcinoma (RCC) ECOG Performance Status of 0 or 1 and for RCC (Part 2 Arm B), Karnofsky performance status ≥ 70% Exclusion Criteria: - History of allergy or hypersensitivity to study drug components Part 1 Arm A: Advanced HCC History of hepatic encephalopathy or evidence of portal hypertension Active coinfection with hepatitis D virus infection in participants with HBV Part 2 Arm A:Metastatic NSCLC - Participants with known ALK translocations and EGFR mutation that are sensitive to available targeted inhibitor therapy Other 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 1 Arm A: mM, mUC, HCC<br>metastatic Melanoma (mM), metastatic Urothelial Carcinoma (mUC), and advanced Heptocellular Carcinoma (HCC) | Drug: ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-734016);Drug: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-936558);Drug: ENHANZE (rHuPH20)<br>* Specified Dose on Specified Days<br>|
| Experimental: Part 1: Arm B: mM<br>metastatic Melanoma (mM) | Drug: ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-734016);Drug: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-936558);|
| Experimental: Part 2: Arm A: NSCLC<br>metastatic non small cell lung cancer (NSCLC) | Drug: ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-734016);Drug: ENHANZE (rHuPH20)<br>* Specified Dose on Specified Days<br>Drug: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-986298);|
| Experimental: Part 2: Arm B: RCC<br>advanced or metastatic renal cell carcinoma (RCC) | Drug: ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-734016);Drug: ENHANZE (rHuPH20)<br>* Specified Dose on Specified Days<br>Drug: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: (BMS-986298);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 Arm A: Average concentration of ipilimumab (Cavg21d) |  | Day 21 | 
| Part 1 Arm A: Area under the concentration in ipilimumab AUC(0-21d) |  | Day 21 | 
| Part 1 Arm A: Maximum observed serum concentration of ipilimumab (Cmax) |  | Up to 21 days | 
| Part 1 Arm A: Observed concentration of ipilimumab at 21 days post dose (C21d) |  | Day 21 | 
| Part 1 Arm A: Time of maximum observed concentration in ipilimumab (Tmax) |  | Up to 21 days | 
| Part 2 Arm A: Average concentration in ipilimumab (Cavg42d) |  | Day 42 | 
| Part 2 Arm A: Area under the concentration in ipilimumab AUC(0-42d) |  | Day 42 | 
| Part 2 Arm A: Maximum observed serum Concentration of Ipilimumab (Cmax) |  | Up to 42 days | 
| Part 2 Arm A: Observed concentration in ipilimumab (C42d) |  | Day 42 | 
| Part 2 Arm A: Time of maximum observed concentration in ipilimumab (Tmax) |  | Up to 42 days | 
| Part 2 Arm B: Average concentration of Ipilimumab at 21 days post dose (Cavg21d) |  | Day 21 | 
| Part 2 Arm B: Area Under the Concentration in Ipilimumab AUC(0-21d) |  | Day 21 | 
| Part 2 Arm B: Maximum observed serum Concentration in Ipilimumab (Cmax) |  | Up to 21 days | 
| Part 2 Arm B: Observed concentration of ipilimumab at 21 days post dose (C21d) |  | Day 21 | 
| Part 2 Arm B: Time of maximum observed concentration in Ipilimumab (Tmax) |  | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 Arm B: Average concentration of ipilimumab without rHuPH20 (Cavg21d) |  | Day 21 | 
| Part 1 Arm B: Area under the concentration in ipilimumab without rHuPH20 AUC(0-21d) |  | Day 21 | 
| Part 1 Arm B: Maximum observed serum concentration of ipilimumab without rHuPH20 (Cmax) |  | Up to 21 days | 
| Part 1 Arm B: Observed concentration of ipilimumab without rHuPH20 at 21 days post dose (C21d) |  | Day 21 | 
| Part 1 Arm B: Time of maximum observed concentration in ipilimumab without rHuPH20 (Tmax) |  | Up to 21 days | 
| Incidence of adverse events (AE's) |  | Up to 2.5 years | 
| Incidence of serious adverse events (SAEs) |  | Up to 5 years | 
| Incidence of AE's leading to discontinuation |  | Up to 2.5 years | 
| Incidence of death |  | Up to 2.5 years | 
| Incidence of laboratory abnormalities |  | Up to 2.5 years | 
| Instance of Anaphylactic occurring within 2 days of study drug administration |  | Up to 2.5 years | 
| Instance of hypersensitivity occurring within 2 days of study drug administration |  | Up to 2.5 years | 
| Incidence of hypersensitivity occurring within 2 days of study drug administration |  | Up to 2.5 years | 
| Incidence of infusion reactions occurring within 2 days of study drug administration |  | Up to 2.5 years | 
| Incidence of injection occurring within 2 days of study drug administration |  | Up to 2.5 years | 
| Percentage of participants who develop anti-ipilimumab antibodies |  | Up to 2.5 years | 
| Percentage of participants who develop anti-nivolumab antibodies |  | Up to 2.5 years | 
| Percentage of participants who have developed neutralizing antibodies |  | Up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, renal cancer, bladder cancer, skin cancer, liver cancer