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

A Phase 1/2 Pharmacokinetic Multi-tumor Study of Subcutaneous Formulation of Ipilimumab Monotherapy and in Combination with Subcutaneous Nivolumab - CheckMate 76U: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 76U

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-004380-40-IT

Enrollment

Registered

2021-06-17

Start date

2020-05-04

Completion date

Unknown

Last updated

2024-10-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

The study population will include participants diagnosed with metastatic melanoma, advanced/metastatic urothelial carcinoma (mUC), advanced hepatocellular carcinoma (HCC) in Part 1, and metastatic squamous or non-squamous non-small cell lung cancer (NSCLC), and metastatic renal cell carcinoma (RCC) in Part 2. MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) M

Interventions

Trade Name: Opdivo (100 mg/10 ml) Product Name: Nivolumab-10 ml vial-COMMERCIAL Product Code: [BMS-936558] Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: NIVOLUMAB CAS

MDX-010 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5- Product Name: Ipilimumab Subcutaneous (administered with or without excipient rHuPH20) Pro

Eligibility

Sex/Gender

All

Inclusion criteria

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% Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16

Exclusion criteria

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 co-infection 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

Design outcomes

Primary

Measure	Time frame
Main Objective: - Part 1 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously as monotherapy -Part 2 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously in combination with SC nivolumab -Part 2 Arm B: To describe the pharmacokinetics of ipilimumab administered subcutaneously with rHuPH20 in combination with SC nivolumab with rHuPH20;Secondary Objective: - Part 1 Arm B: To describe the pharmacokinetics of ipilimumab without rHuPH20 administered subcutaneously as monotherapy - Part 1 Arm A: To assess the safety profile of SC ipilimumab with rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination - Part 1 Arm B: To assess the safety profile of SC ipilimumab without rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination - Part 2 Arms A/B: To assess the safety profile of SCipilimumab with rHuPH20 in combination with SC nivolumab with rHuPH20 - Part 1 Arms A/B and Part 2 Arms A/B: To evaluate incidence of AEs in the broad standardized MedDRA query (SMQ) of Anaphylactic Reaction and the select AE hypersensitivity/injection/infusion reaction category - Part 1 Arms A/B: To assess the immunogenicity of SC ipilimumab - Part 2 Arms A/B: To assess the immunogenicity of SC ipilimumab and SC nivolumab;Primary end point(s): 1) Part 1 Arm A: Average concentration of ipilimumab (Cavg21d) 2) Part 1 Arm A: Area under the concentration in ipilimumab AUC(0-21d) 3) Part 1 Arm A: Maximum observed serum concentration of ipilimumab (Cmax) 4) Part 1 Arm A: Observed concentration of ipilimumab (C21d) 5) Part 1 Arm A: Time of maximum observed concentration in ipilimumab (Tmax) 6) Part 2 Arm A: Average concentration in ipilimumab (Cavg42d) 7) Part 2 Arm A: Area under the concentration in ipilimumab AUC(0-42d) 8) Part 2 Arm A: Maximum observed serum Concentration of Ipilimumab (Cmax) 9) Part 2 Arm A: Observed concentration in ipilimumab (C42d) 10) Part 2 Arm A: Time of maximum obs	—

Measure

Time frame

Main Objective: - Part 1 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously as monotherapy -Part 2 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously in combination with SC nivolumab -Part 2 Arm B: To describe the pharmacokinetics of ipilimumab administered subcutaneously with rHuPH20 in combination with SC nivolumab with rHuPH20;Secondary Objective: - Part 1 Arm B: To describe the pharmacokinetics of ipilimumab without rHuPH20 administered subcutaneously as monotherapy - Part 1 Arm A: To assess the safety profile of SC ipilimumab with rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination - Part 1 Arm B: To assess the safety profile of SC ipilimumab without rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination - Part 2 Arms A/B: To assess the safety profile of SCipilimumab with rHuPH20 in combination with SC nivolumab with rHuPH20 - Part 1 Arms A/B and Part 2 Arms A/B: To evaluate incidence of AEs in the broad standardized MedDRA query (SMQ) of Anaphylactic Reaction and the select AE hypersensitivity/injection/infusion reaction category - Part 1 Arms A/B: To assess the immunogenicity of SC ipilimumab - Part 2 Arms A/B: To assess the immunogenicity of SC ipilimumab and SC nivolumab;Primary end point(s): 1) Part 1 Arm A: Average concentration of ipilimumab (Cavg21d) 2) Part 1 Arm A: Area under the concentration in ipilimumab AUC(0-21d) 3) Part 1 Arm A: Maximum observed serum concentration of ipilimumab (Cmax) 4) Part 1 Arm A: Observed concentration of ipilimumab (C21d) 5) Part 1 Arm A: Time of maximum observed concentration in ipilimumab (Tmax) 6) Part 2 Arm A: Average concentration in ipilimumab (Cavg42d) 7) Part 2 Arm A: Area under the concentration in ipilimumab AUC(0-42d) 8) Part 2 Arm A: Maximum observed serum Concentration of Ipilimumab (Cmax) 9) Part 2 Arm A: Observed concentration in ipilimumab (C42d) 10) Part 2 Arm A: Time of maximum obs

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Secondary

Measure	Time frame
Secondary end point(s): 1) Part 1 Arm B: Average concentration of ipilimumab without rHuPH20 (Cavg21d) 2) Part 1 Arm B: Area under the concentration in ipilimumab without rHuPH20 AUC(0-21d) 3) Part 1 Arm B: Maximum observed serum concentration of ipilimumab without rHuPH20 (Cmax) 4) Part 1 Arm B: Observed concentration of ipilimumab without rHuPH20 (C21d) 5) Part 1 Arm B: Time of maximum observed concentration in ipilimumab without rHuPH20 (Tmax) 6) Incidence of adverse events (AE's) 7) Incidence of serious adverse events (SAEs) 8) Incidence of AE's leading to discontinuation 9) Incidence of death 10) Incidence of laboratory abnormalities 11) Instance of Anaphylactic occurring within 2 days of study drug administration 12) Instance of hypersensitivity occurring within 2 days of study drug administration 13) Incidence of hypersensitivity occurring within 2 days of study drug administration 14) Incidence of infusion reactions occurring within 2 days of study drug administration 15) Incidence of injection occurring within 2 days of study drug administration 16) Percentage of participants who develop anti-ipilimumab antibodies 17) Percentage of participants who develop anti-nivolumab antibodies 18) Percentage of participants who have developed neutralizing antibodies;Timepoint(s) of evaluation of this end point: 1) Day 21 2) Day 21 3) Up to 21 days 4) Day 21 5) Up to 21 days 6) Up to 2.5 years 7) Up to 5 years 8) Up to 2.5 years 9) Up to 2.5 years 10) Up to 2.5 years 11) Up to 2.5 years 12) Up to 2.5 years 13) Up to 2.5 years 14) Up to 2.5 years 15) Up to 2.5 years 16) Up to 2.5 years 17) Up to 2.5 years 18) Up to 2.5 years	—

Measure

Time frame

Secondary end point(s): 1) Part 1 Arm B: Average concentration of ipilimumab without rHuPH20 (Cavg21d) 2) Part 1 Arm B: Area under the concentration in ipilimumab without rHuPH20 AUC(0-21d) 3) Part 1 Arm B: Maximum observed serum concentration of ipilimumab without rHuPH20 (Cmax) 4) Part 1 Arm B: Observed concentration of ipilimumab without rHuPH20 (C21d) 5) Part 1 Arm B: Time of maximum observed concentration in ipilimumab without rHuPH20 (Tmax) 6) Incidence of adverse events (AE's) 7) Incidence of serious adverse events (SAEs) 8) Incidence of AE's leading to discontinuation 9) Incidence of death 10) Incidence of laboratory abnormalities 11) Instance of Anaphylactic occurring within 2 days of study drug administration 12) Instance of hypersensitivity occurring within 2 days of study drug administration 13) Incidence of hypersensitivity occurring within 2 days of study drug administration 14) Incidence of infusion reactions occurring within 2 days of study drug administration 15) Incidence of injection occurring within 2 days of study drug administration 16) Percentage of participants who develop anti-ipilimumab antibodies 17) Percentage of participants who develop anti-nivolumab antibodies 18) Percentage of participants who have developed neutralizing antibodies;Timepoint(s) of evaluation of this end point: 1) Day 21 2) Day 21 3) Up to 21 days 4) Day 21 5) Up to 21 days 6) Up to 2.5 years 7) Up to 5 years 8) Up to 2.5 years 9) Up to 2.5 years 10) Up to 2.5 years 11) Up to 2.5 years 12) Up to 2.5 years 13) Up to 2.5 years 14) Up to 2.5 years 15) Up to 2.5 years 16) Up to 2.5 years 17) Up to 2.5 years 18) Up to 2.5 years

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Countries

Australia, Brazil, France, Italy, Netherlands, New Zealand, United Kingdom, United States

Contacts

Public ContactGCT-SU

Bristol-Myers Squibb International Corporation

clinical.trials@bms.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026