INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC)

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Colorectal Cancer; Ovarian Cancer; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Bladder Cancer; Triple Negative Breast Cancer; Pancreatic Ductal Adenocarcinoma; Castration Resistant Prostate Cancer; Gastric/ Gastroesophageal Junction; Squamous Carcinoma of the Anal Canal
• Intervention / Treatment: Drug: INCB106385; Drug: INCMGA00012

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 01200
    • Cliniques Universitaires Ucl Saint-Luc
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• France
  • Bordeaux, France, 33000
    • Institut Bergonie
  • Toulouse, France, 31059
    • Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Italy
  • Modena, Italy, 41124
    • A.O.U. Di Modena - Policlinico
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori Irccs Fondazione Pascale
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra (CUN)
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Glasgow, United Kingdom, G12 0YN
    • University of Glasgow
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust - Hammersmith Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BV
    • The Christie Nhs Foundation Trust Uk
• United States
  • California
    • West Hollywood, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland-Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to comprehend and willingness to sign an ICF.
• Willing and able to conform to and comply with all Protocol requirements.
• Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian cancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment with available therapies (including anti PD-(L)1 therapy (if applicable).
• Willingness to undergo pre- and on-treatment tumor biopsy.
• Have CD8 T-cell-positive tumors.
• Presence of measurable disease according to RECIST v1.1.
• ECOG performance status 0 to 1.
• Life expectancy > 12 weeks.
• Willingness to avoid pregnancy or fathering children based.
• Acceptable laboratory parameters

Exclusion Criteria:

• Clinically significant cardiac disease.
• Known or active CNS metastases and/or carcinomatous meningitis.
• Active or inactive autoimmune disease or syndrome that required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease..
• 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.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy 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.
• 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.
• Concomitant treatment with strong CYP3A4 inhibitors or inducers.
• Receipt of a live 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.
• Evidence of HBV or HCV infection or risk of reactivation.
• Known history of HIV (HIV 1/2 antibodies).
• History of organ transplant, including allogeneic stem-cell transplantation.
• Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.
• Presence of a gastrointestinal condition that may affect drug absorption.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study,pose a significant risk to the participant; or interfere with interpretation of study data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A (TGA) - INCB106385; In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.	Drug: INCB106385; INCB106385 will be administered orally QD
Experimental: Treatment Group B (TGB) - INCB106385+INCMGA00012; In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.	Drug: INCB106385; INCB106385 will be administered orally QD; Drug: INCMGA00012; INCMGA0012 will be administered IV once every 4 weeks (Q4W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent adverse events (TEAE)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after last dose of study drug.	Up to Approximately 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of INCB106385 as a single agent or in combination with INCMGA00012	Maximum observed plasma concentration.	Up to 6 months
Tmax of INCB106385 as a single agent or in combination with INCMGA00012	Time to maximum plasma concentration	Up to 6 months
Cmin of INCB106385 as a single agent or in combination with INCMGA00012	Minimum observed plasma concentration over the dose interval	Up to 6 months
AUC of INCB106385 as a single agent or in combination with INCMGA00012	Area under the plasma concentration-time curve	Up to 6 months
CL/F of INCB106385 as a single agent or in combination with INCMGA00012	Apparent oral dose clearance	Up to 6 months
Objective Response Rate (ORR)	Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1.	Up to approximately 24 months
Disease Control Rate	Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1.	Up to approximately 24 months
Duration Of Response (DOR)	Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression.	Up to approximately 24 months
Change in tumoral gene expression	Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline	Predose and Week 5-6
Change in immune cell activation in tumors	Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline	Predose and Week 5-6

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Ilona Rybicka, M.D, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: PD-1; Advanced Solid Tumors; INCB106385
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Neoplasms, Squamous Cell; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Triple Negative Breast Neoplasms
• Other Study ID Numbers: INCB 106385-102; 2020-002921-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No