A Study Evaluating the Drug Levels of Iplimumab Given Under the Skin Alone and in Combination With Nivolumab in Multiple Tumor Types (CheckMate 76U)

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

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

Study Overview

• Status: Terminated
• Conditions: Tumor
• Intervention / Treatment: Drug: ipilimumab; Drug: nivolumab; Drug: ENHANZE (rHuPH20)

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapie
  • Rozzano, Italy, 20089
    • Humanitas-U.O di Oncologia medica ed Ematologia
  • Siena, Italy, 53100
    • ospedale le scotte-U.O.C. Immunoterapia Oncologica
• New Zealand
  • Auckland, New Zealand, 1023
    • Local Institution - 0010
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Local Institution - 0020
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Local Institution - 0013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Arm A: mM, mUC, HCC; metastatic Melanoma (mM), metastatic Urothelial Carcinoma (mUC), and advanced Heptocellular Carcinoma (HCC)	Drug: ipilimumab; Specified Dose on Specified Days; Other Names: (BMS-734016); Drug: nivolumab; Specified Dose on Specified Days; Other Names: (BMS-986298); Drug: ENHANZE (rHuPH20); Specified Dose on Specified Days
Experimental: Part 1: Arm B: mM; metastatic Melanoma (mM)	Drug: ipilimumab; Specified Dose on Specified Days; Other Names: (BMS-734016); Drug: nivolumab; Specified Dose on Specified Days; Other Names: (BMS-986298)
Experimental: Part 2: Arm A: NSCLC; metastatic non small cell lung cancer (NSCLC)	Drug: ipilimumab; Specified Dose on Specified Days; Other Names: (BMS-734016); Drug: nivolumab; Specified Dose on Specified Days; Other Names: (BMS-986298); Drug: ENHANZE (rHuPH20); Specified Dose on Specified Days
Experimental: Part 2: Arm B: RCC; advanced or metastatic renal cell carcinoma (RCC)	Drug: ipilimumab; Specified Dose on Specified Days; Other Names: (BMS-734016); Drug: nivolumab; Specified Dose on Specified Days; Other Names: (BMS-986298); Drug: ENHANZE (rHuPH20); Specified Dose on Specified Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2020
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: lung cancer, renal cancer, bladder cancer, skin cancer, liver cancer
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-76U

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No