Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

Incyte

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Cancer; Advanced Malignancies

Treatments: Drug: Ipilimumab; Drug: Nivolumab; Drug: INCAGN01876

Study type: Interventional

Funder types: Industry

Identifiers

NCT03126110

INCAGN 1876-201

2016-004989-25 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies in subjects with advanced or metastatic malignancies.

Enrollment: 145 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Phase 1: Subjects with advanced or metastatic solid tumors.
• Phase 1: Subjects who have disease progression after treatment with available therapies.
• Phase 2: Subjects with advanced or metastatic cervical cancer, gastric cancer (including stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN and PD-1/PD-L1 relapsed melanoma.
• Presence of measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

Exclusion criteria

• Laboratory and medical history parameters not within the Protocol-defined range
• Prior treatment with any tumor necrosis factor super family agonist.
• Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
• Active autoimmune disease.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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145 participants in 17 patient groups

Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 1.0 milligrams per kilogram (mg/kg) administered intravenously (IV) every 2 weeks (Q2W) in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Experimental group

Description:

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 5.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Experimental group

Description:

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W).

Treatment:

Drug: INCAGN01876

Drug: Ipilimumab

Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Experimental group

Description:

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Treatment:

Drug: INCAGN01876

Drug: Ipilimumab

Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Experimental group

Description:

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Treatment:

Drug: INCAGN01876

Drug: Ipilimumab

Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab

Experimental group

Description:

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with nivolumab 3 mg/kg administered IV Q2W and ipilimumab 1 mg/kg administered IV Q6W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Drug: Ipilimumab

Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg

Experimental group

Description:

Participants with programmed cell death protein/programmed cell death ligand 1 (PD-1/PD-L1) relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Treatment:

Drug: INCAGN01876

Drug: Ipilimumab

Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg

Experimental group

Description:

Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg

Experimental group

Description:

Participants with squamous cell carcinoma of the head and neck (SCCHN) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg

Experimental group

Description:

Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg

Experimental group

Description:

Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab

Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg

Experimental group

Description:

Participants with gastric cancer, squamous cell carcinoma of the head and neck, cervical cancer, or PD-1/PD-L1 relapsed melanoma who had tumor lesions that were amenable to percutaneous biopsy received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Treatment:

Drug: INCAGN01876

Drug: Nivolumab