Study of INCA 0186 in Subjects With Advanced Solid Tumors

NCT ID: NCT04989387

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-04
• Study Completion Date: 2024-09-19

Brief Summary

This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCA00186 when given alone or in combination with INCB106385 and/or retifanlimab in participants with specific advanced solid tumors; squamous cell carcinoma of the head and neck (SCCHN) and specified gastrointestinal (GI) malignancies have been selected as indications of interest for this study. Participants with CD8 T-cell-positive tumors will be selected as these tumors are more likely to respond to immunotherapy.

Conditions

Advanced Solid Tumors; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Gastrointestinal (GI) Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group A Dose Escalation and Expansion

INCA00186 will be administered as monotherapy every 2 or every 4 weeks.

Group Type: EXPERIMENTAL

INCA00186

Intervention Type: DRUG

INCA00186 will be administered every 2 weeks or 4 weeks as per protocol

Treatment Group B1 Dose Escalation and Expansion

INCA00186 will be administered in combination with retifanlimab. INCA00186 will be administered every 2 or 4 weeks and retifanlimab will be administered every 4 weeks.

Group Type: EXPERIMENTAL

INCA00186

Intervention Type: DRUG

INCA00186 will be administered every 2 weeks or 4 weeks as per protocol

Retifanlimab

Intervention Type: DRUG

Retifanlimab will be administered every 4 weeks as per protocol

Treatment Group B2 Dose Escalation and Expansion

INCA00186 will be administered in combination with INCB106385. INCA00186 will be administered every 2 or 4 weeks and INCB106385 will be administered once or twice daily.

Group Type: EXPERIMENTAL

INCA00186

Intervention Type: DRUG

INCA00186 will be administered every 2 weeks or 4 weeks as per protocol

INCB106385

Intervention Type: DRUG

INCB106385 will be administered orally once or twice a day.

Treatment Group C Dose Escalation and Expansion

INCA00186 will be administered in combination with retifanlimab and INCB106385. INCA00186 will be administered every 2 to 4 weeks, retifanlimab every 4 weeks and INCB106385 once or twice daily.

Group Type: EXPERIMENTAL

INCA00186

Intervention Type: DRUG

INCA00186 will be administered every 2 weeks or 4 weeks as per protocol

Retifanlimab

Intervention Type: DRUG

Retifanlimab will be administered every 4 weeks as per protocol

INCB106385

Intervention Type: DRUG

INCB106385 will be administered orally once or twice a day.

Interventions

INCA00186

INCA00186 will be administered every 2 weeks or 4 weeks as per protocol

Intervention Type: DRUG

Retifanlimab

Retifanlimab will be administered every 4 weeks as per protocol

Intervention Type: DRUG

INCB106385

INCB106385 will be administered orally once or twice a day.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ability to comprehend and willingness to sign a written ICF for the study.
• Male or female participant aged 18 years or older inclusive at the time of signing the ICF.
• Must be willing and able to conform to and comply with all Protocol requirements
• Willingness to undergo pre- and on-treatment tumor biopsy.
• Have CD8 T-cell-positive tumors
• ECOG performance status 0 or 1.
• Measurable disease according to RECIST v1.1.
• Participants with SCCHN: Participants with histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy).
• Participants with specified GI malignancies: Histologically or cytologically confirmed advanced or metastatic colorectal (CRC), gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), or squamous carcinoma of the anal canal (SCAC).
• Participants should have disease progression after treatment with available therapies, including anti-PD-(L)1 therapy (if applicable), that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.
• For participants to be enrolled in cohorts including INCB106385: The ability to swallow oral medication.
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria

• Clinically significant cardiac disease, unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, and New York Heart Association Class III or IV congestive heart failure.
• History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful.
• Known active CNS metastases and/or carcinomatous meningitis.
• Participants who have active or inactive autoimmune disease or syndrome (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
• Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of the first dose of study treatment with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease free > 1 year after treatment with curative intent.
• Participants with protocol specified exclusionary hematology, hepatic, renal and coagulation laboratory values at screening.

Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting study treatment.

• Evidence of interstitial lung disease, history of interstitial lung disease, or active noninfectious pneumonitis.
• Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended, OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage.
• Prior treatment with any adenosine pathway targeting drugs.
• Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• Any prior radiation therapy within 28 days before the first dose of study treatment.
• Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• For participants to be enrolled in cohorts including INCB106385: concomitant treatment with strong CYP3A4 inhibitors or inducers.
• Receipt of a live virus vaccine within 30 days of the first dose of study treatment.
• Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of the first dose of study treatment.
• Known or suspected SARS-CoV-2 infection at the time of enrollment.
• Active HBV or HCV infection that requires treatment. HBV-DNA and HCV-RNA must be undetectable. Participants who have cleared a prior HBV infection (defined as HBsAg negative, HBsAg antibody positive, and anti-HBc antibody positive) are eligible for the study.
• Known history of HIV (HIV 1/2 antibodies).
• History of organ transplant, including allogeneic stem-cell transplantation or CAR-T cell therapy.
• Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.
• For participants to be enrolled in cohorts including INCB106385: Inability to swallow food or any concomitant condition of the upper GI tract that precludes administration of oral medications.
• Is pregnant or breastfeeding.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ilona Rybicka, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Emory University

Atlanta, Georgia, United States

University of Maryland-Greenebaum Cancer Center

Baltimore, Maryland, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Carolina Bio-Oncology Institute, Pllc

Huntersville, North Carolina, United States

Vanderbilt Medical Center

Nashville, Tennessee, United States

Md Anderson Cancer Center

Houston, Texas, United States

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Innsbruck University Hospital

Innsbruck, , Austria

Landeskrankenhaus Salzburg

Salzburg, , Austria

Cliniques Universitaires Ucl Saint-Luc

Brussels, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, , Belgium

Ghent University Hospital

Ghent, , Belgium

Universitair Ziekenhuis (Uz) Leuven

Leuven, , Belgium

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Radboud University Nijmegen Medical Center

Nijmegen, , Netherlands

Erasmus Mc Cancer Institute

Rotterdam, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Hospital General Universitario Vall D Hebron

Barcelona, , Spain

Institut Catala Doncologia Ico - Hospital Duran I Reynals Location

Barcelona, , Spain

Fundacion Jimenez Diaz University Hospital

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Clinico Universitario Virgen de La Victoria

Málaga, , Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Cambridge University Hospitals Nhs Foundation Trust

Cambridge, , United Kingdom

Guys and St Thomas Nhs Foundation Trust

London, , United Kingdom

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, , United Kingdom

The Christie Nhs Foundation Trust Uk

Manchester, , United Kingdom

Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust

Newcastle upon Tyne, , United Kingdom

The Royal Marsden Nhs Foundation Trust - Chelsea

Sutton, , United Kingdom

Countries

United States; Austria; Belgium; Netherlands; Spain; United Kingdom

Other Identifiers

2021-001263-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCA 0186-101

Identifier Type: -

Identifier Source: org_study_id