Study of INCA 0186 in Subjects With Advanced Solid Tumors

NCT04989387 | Terminated Phase 1 FDA Drug

• 2 other identifiers: INCA 0186-1012021-001263-24
• Study Type: interventional
• Target: 57
• Locations: 6 countries
• Sites: 32

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

Keywords

open label; advanced solid tumors; squamous cell carcinoma of the head and neck; gastrointestinal malignancies; gastric/gastroesophageal junction cancer; hepatocellular carcinoma; pancreatic ductal adenocarcinoma; squamous carcinoma of the anal canal; colorectal cancer

Outcome Measures

Primary Outcomes (3)

• Evaluation of the safety and tolerability of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by the number of participants with adverse eventsductions and withdrawal of treatment due to AEs

  90 days after study completion totaling up to 27 months

• Evaluation of Dose-Limiting Toxicity (DLTs) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety events during treatment

  90 days after study completion totaling up to 27 months

• Evaluation of Recommended Dose for Expansion (RDE) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety, PK and PD data

  90 days after study completion totaling up to 27 months

Secondary Outcomes (11)

• Determination of PK parameter Maximum Observed Plasma Concentration (Cmax) for INCA00186

  Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months

• Determination of PK parameter of Time to Maximum Plasma Concentration (tmax) for INCA00186

  Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months

• Determination of PK parameter of concentration at the end of the dosing interval (Ctau) for INCA00186

  Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months

• Determination of PK parameter of area under the plasma or serum concentration-time curve (AUC) for INCA00186

  Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months

• Determination of PK parameter of total clearance (CL) for INCA00186

  Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months

Study Arms (4)

Treatment Group A Dose Escalation and Expansion

EXPERIMENTAL

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

Drug: INCA00186

Treatment Group B1 Dose Escalation and Expansion

EXPERIMENTAL

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.

Drug: INCA00186; Drug: Retifanlimab

Treatment Group B2 Dose Escalation and Expansion

EXPERIMENTAL

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.

Drug: INCA00186; Drug: INCB106385

Treatment Group C Dose Escalation and Expansion

EXPERIMENTAL

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.

Drug: INCA00186; Drug: Retifanlimab; Drug: INCB106385

Interventions

INCA00186 DRUG

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

Treatment Group A Dose Escalation and Expansion; Treatment Group B1 Dose Escalation and Expansion; Treatment Group B2 Dose Escalation and Expansion; Treatment Group C Dose Escalation and Expansion

Retifanlimab DRUG

Retifanlimab will be administered every 4 weeks as per protocol

Treatment Group B1 Dose Escalation and Expansion; Treatment Group C Dose Escalation and Expansion

INCB106385 DRUG

INCB106385 will be administered orally once or twice a day.

Treatment Group B2 Dose Escalation and Expansion; Treatment Group C Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (32)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Maryland-Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Carolina Bio-Oncology Institute, Pllc

Huntersville, North Carolina, 28078, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Innsbruck University Hospital

Innsbruck, A-6020, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 05020, Austria

Location

Cliniques Universitaires Ucl Saint-Luc

Brussels, 01200, Belgium

Location

Institut Jules Bordet

Brussels, B-1070, Belgium

Location

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, 02650, Belgium

Location

Ghent University Hospital

Ghent, 09000, Belgium

Location

Universitair Ziekenhuis (Uz) Leuven

Leuven, 03000, Belgium

Location

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

Radboud University Nijmegen Medical Center

Nijmegen, 6525 GA, Netherlands

Location

Erasmus Mc Cancer Institute

Rotterdam, 3015GD, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital General Universitario Vall D Hebron

Barcelona, 08035, Spain

Location

Institut Catala Doncologia Ico - Hospital Duran I Reynals Location

Barcelona, 199203, Spain

Location

Fundacion Jimenez Diaz University Hospital

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario Virgen de La Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Cambridge University Hospitals Nhs Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Guys and St Thomas Nhs Foundation Trust

London, SE1 9RT, United Kingdom

Location

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

The Christie Nhs Foundation Trust Uk

Manchester, M20 4BV, United Kingdom

Location

Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust - Chelsea

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasms; Carcinoma, Hepatocellular; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ilona Rybicka, MD

  Incyte Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 4, 2021
• Study Start: October 4, 2021
• Primary Completion: September 19, 2024
• Study Completion: September 19, 2024
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); GB (6); US (8); BE (5); AU (2); NL (5)