A Study Exploring the Safety and Efficacy of INCAGN01949 in Combination With Immune Therapies in Advanced or Metastatic Malignancies

NCT03241173 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: INCAGN 1949-201
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies.

Conditions

Advanced Malignancies

Keywords

advanced or metastatic cervical cancer; endometrial cancer; esophageal cancer; hepatocellular carcinoma (HCC); melanoma; Merkel cell carcinoma; mesothelioma; microsatellite instability-high colorectal cancer; non-small cell lung cancer (NSCLC); ovarian cancer; squamous cell carcinoma of the head and neck; small cell lung cancer (SLCL); renal cell carcinoma (RCC); triple-negative breast cancer; TNBC; urothelial carcinoma; OX40 ligand (OX40); SCCHN; MSI-H CRC; gastric cancer (including stomach and gastroesophageal junction [GEJ])

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results that occurred after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

  up to 17.4 months

• Phase 1: Number of Participants With a Grade 3 or Higher TEAE

  An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death due to AE.

  up to 17.4 months

• Phase 2: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of progressive disease (PD). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

  up to 24 months

Secondary Outcomes (11)

• Phase 1: ORR

  up to 15.6 months

• Phase 1: Duration of Response (DOR)

  up to 11.0 months

• Phase 2: DOR

  up to 24 months

• Phase 1: Disease Control Rate (DCR)

  up to 15.6 months

• Phase 2: DCR

  up to 24 months

Study Arms (7)

Phase 1, Dose Escalation: INCAGN01949 + Nivolumab

EXPERIMENTAL

INCAGN01949 (70, 200, 350, or 700 milligrams \[mg\]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors

Drug: INCAGN01949; Drug: Nivolumab

Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab

EXPERIMENTAL

INCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors

Drug: INCAGN01949; Drug: Ipilimumab

Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab

EXPERIMENTAL

INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors

Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab

Phase 1, Safety Expansion: INCAGN01949 + Nivolumab

EXPERIMENTAL

Run-in with INCAGN01949 (70, 200, or 350 mg) x 2 doses, followed by INCAGN01949 (70, 200, or 350 mg) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors

Drug: INCAGN01949; Drug: Nivolumab

Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab

EXPERIMENTAL

Run-in with INCAGN01949 x 2 doses, followed by INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors

Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab

Phase 2, Part A: INCAGN01949 + nivolumab

EXPERIMENTAL

INCAGN01949 combined with nivolumab in programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) refractory participants with gastric cancer, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC)

Drug: INCAGN01949; Drug: Nivolumab

Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab

EXPERIMENTAL

INCAGN01949 alone, combined with nivolumab, and combined with nivolumab and ipilimumab in PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC

Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab

Interventions

INCAGN01949 DRUG

In Phase 1, participants will receive INCAGN01949 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will receive INCAGN01949 administered IV at the recommended dose from Phase 1.

Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab; Phase 1, Dose Escalation: INCAGN01949 + Nivolumab; Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab; Phase 1, Safety Expansion: INCAGN01949 + Nivolumab; Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab; Phase 2, Part A: INCAGN01949 + nivolumab; Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab

Nivolumab DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1, Dose Escalation: INCAGN01949 + Nivolumab; Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab; Phase 1, Safety Expansion: INCAGN01949 + Nivolumab; Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab; Phase 2, Part A: INCAGN01949 + nivolumab; Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab

Ipilimumab DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab; Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab; Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab; Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 gastric cancer, SCCHN, NSCLC, or RCC and are considered refractory to prior PD-1/L1 therapy.
• Presence of measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

You may not qualify if:

• Laboratory and medical history parameters not within the Protocol-defined range
• 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.

Sponsors & Collaborators

• Incyte Biosciences International Sàrl: lead

Study Sites (15)

The University of Alabama Birmingham (UAB)

Birmingham, Alabama, 90025, United States

Location

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85258, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Mount Sinai Medical Center of Florida, Inc.

Miami, Florida, 33140, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

John Theurer Cancer Center At Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

Rutgers, The State University

New Brunswick, New Jersey, 08901, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Institute, LLC (SCRI)

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Endometrial Neoplasms; Esophageal Neoplasms; Carcinoma, Hepatocellular; Melanoma; Carcinoma, Merkel Cell; Mesothelioma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Squamous Cell Carcinoma of Head and Neck; Small Cell Lung Carcinoma; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell; Stomach Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenoma; Neoplasms, Mesothelial; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Squamous Cell; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Because there was limited clinical efficacy, with 3 confirmed responders, Phase 2 of the study did not open for enrollment. There were no safety concerns.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• John E. Janik, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 7, 2017
• Study Start: October 9, 2017
• Primary Completion: September 17, 2019
• Study Completion: September 17, 2019
• Last Updated: September 27, 2022
• Results First Posted: September 27, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)