A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

August 24, 2026 updated by: Incyte Corporation

A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Monica, California, United States, 90404
        • UCLA Healthcare Hematology-Oncology
    • Colorado
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institue At Healthone
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Hospital
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • Maryland
      • Baltimore, Maryland, United States, 21287-7049
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Jefferson University Hospitals
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI Oncology Partners
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥18 years old.
  • Locally advanced or metastatic solid tumor with KRAS G12D mutation.
  • For Part 1 and Part 2 Combination Group 1: Disease progression on or after prior standard treatment, or intolerance to or ineligibility for standard treatment, or no standard available treatment to improve the disease outcome.
  • For Part 2 Combination Groups 2 and 3: No more than 1 prior standard treatment.

  • Cohort-specific requirements as follows:

    • Parts 1a and 1d: histologically or cytologically confirmed malignant solid tumor of any tissue origin.

    • Part 1b

      • Disease Group 1: diagnosis of PDAC and at least 1 but no more than 2 prior standard systemic regimens for pancreatic cancer.
      • Disease Group 2: diagnosis of CRC.
    • Part 1c: Confirmed diagnosis of PDAC or CRC.

    • Parts 2a and 2b

      • Combination Group 1 (INCB186748 in combination with cetuximab):

        • Diagnosis of PDAC or

        • Diagnosis of CRC and ∘ Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and

          • In Part 2a: ≤ 3 prior standard regimens.
          • In Part 2b: ≤ 2 prior standard regimens.
      • Combination Group 2 (INCB186748 in combination with GEMNabP) and

      • Combination Group 3 (INCB186748 in combination with mFOLFIRINOX):

        • Diagnosis of PDAC.
        • ≤ 1 prior standard systemic regimen for pancreatic cancer.
  • Measurable disease according to RECIST v1.1.
  • ECOG performance status score of 0 or 1.

Exclusion Criteria:

  • Prior treatment with any KRAS inhibitor.
  • Known additional invasive malignancy within 1 year of the first dose of study drug.
  • History of organ transplant, including allogeneic stem cell transplantation.
  • Significant, uncontrolled medical condition.
  • History or presence of an ECG abnormality.
  • Inadequate organ function.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1d: Food-Effect
Evaluate food effect on drug exposure as defined in the protocol.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.
Experimental: Part 1a: Dose Escalation monotherapy
INCB186748 at the protocol-defined dose strength based on cohort assignment.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.
Experimental: Part 1b: Dose Expansion monotherapy
INCB186748 at the protocol-defined dose strength based on cohort assignment.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.
Experimental: Part 1c: Pharmacodynamic cohort
INCB186748 at the protocol-defined dose strength based on cohort assignment.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.
Experimental: Part 2a: Dose Escalation combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
Drug: Cetuximab
Cetuximab will be administered at protocol defined dose.
Drug: GEMNabP
GEMNabP will be administered at protocol defined dose.
Drug: mFOLFIRINOX
mFOLFIRINOX will be administered at protocol defined dose.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.
Experimental: Part 2b: Dose Expansion combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
Drug: Cetuximab
Cetuximab will be administered at protocol defined dose.
Drug: GEMNabP
GEMNabP will be administered at protocol defined dose.
Drug: mFOLFIRINOX
mFOLFIRINOX will be administered at protocol defined dose.
Drug: INCB186748
INCB186748 will be administered at protocol defined dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Up to 28 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to approximately 12 months and 60 days
Defined as adverse events reported for the first time or worsening of a pre-existing event occurring after the first dose of study drug up to 30 days (for INCB186748 as monotherapy and in combination with GEMNabP or mFOLFIRINOX) and 60 days (for INCB186748 in combination with cetuximab) after the last dose of INCB186748.
Up to approximately 12 months and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation
Time Frame: Up to approximately 12 months and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation.
Up to approximately 12 months and 60 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
INCB186748 pharmacokinetic (PK) in Plasma
Time Frame: Up to approximately 12 months
INCB186748 concentration in plasma.
Up to approximately 12 months
Objective Response Rate (ORR)
Time Frame: Up to approximately 12 months
Defined as having a best overall Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Up to approximately 12 months
Disease Control Response (DCR)
Time Frame: Up to approximately 12 months
Defined as having a best overall response of CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Up to approximately 12 months
Duration of Response (DOR)
Time Frame: Up to approximately 12 months
Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or death due to any cause if occurring sooner than progression.
Up to approximately 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Investigators

  • Study Director: Incyte Medical Monitor, Incyte Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2025

Primary Completion (Estimated)

March 27, 2027

Study Completion (Estimated)

March 27, 2027

Study Registration Dates

First Submitted

February 5, 2025

First Submitted That Met QC Criteria

February 5, 2025

First Posted (Actual)

February 10, 2025

Study Record Updates

Last Update Posted (Actual)

August 25, 2026

Last Update Submitted That Met QC Criteria

August 24, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCB186748-101
  • 2024-519018-30-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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