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

Launched by INCYTE CORPORATION · Feb 5, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called INCB186748 for patients with advanced or metastatic solid tumors that have a specific genetic change known as the KRAS G12D mutation. The goal is to see how well this medication works for patients who have not responded to standard treatments or who cannot receive typical therapies. The trial is currently looking for participants aged 18 and older who have been diagnosed with these types of tumors and meet specific criteria, such as having a certain number of prior treatments.

If you decide to participate, you will receive the study drug and be monitored for your health and response to the treatment. All genders are welcome to join, and the trial is designed to gather important information about how effective and safe this medication is for people with these challenging conditions. If you have questions about your eligibility or what participating involves, the study team will be there to provide more details and support you throughout the process.

Gender

ALL

Eligibility 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.