Evaluating INCB186748 for advanced solid tumors with KRAS G12D mutation

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

Phase 1 Interventional Incyte Corporation · NCT06818812

This study is testing a new drug called INCB186748 to see if it can help people with advanced solid tumors that have a specific KRAS G12D mutation feel better and improve their health.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment308 (estimated)
Ages18 Years and up
SexAll
SponsorIncyte Corporation Industry-sponsored
Drugs / interventionscetuximab, chemotherapy
Locations9 sites (Santa Monica, California and 8 other locations)
Trial IDNCT06818812 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy of INCB186748 in patients with advanced or metastatic solid tumors that have the KRAS G12D mutation. Participants will receive INCB186748, potentially in combination with other treatments like Cetuximab and GEMNabP or mFOLFIRINOX, depending on their specific cancer type and treatment history. The study aims to determine the safety and effectiveness of these interventions in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced or metastatic solid tumors that have the KRAS G12D mutation.

Not a fit: Patients without the KRAS G12D mutation or those with early-stage tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat solid tumors harboring the KRAS G12D mutation.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Santa Monica, California and 8 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Solid TumorsINCB186748KRASG12D Mutationpancreatic ductal adenocarcinomacolorectal cancer
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.