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

Incyte

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumors

Treatments: Drug: mFOLFIRINOX; Drug: Cetuximab; Drug: INCB186748; Drug: GEMNabP

Study type: Interventional

Funder types: Industry

Identifiers

NCT06818812

INCB186748-101

2024-519018-30-00 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 6 patient groups

Part 1a: Dose Escalation monotherapy

Experimental group

Description:

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Treatment:

Drug: INCB186748

Part 1b: Dose Expansion monotherapy

Experimental group

Description:

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Treatment:

Drug: INCB186748

Part 1c: Pharmacodynamic cohort

Experimental group

Description:

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Treatment:

Drug: INCB186748

Part 1d: Food-Effect

Experimental group

Description:

Evaluate food effect on drug exposure as defined in the protocol.

Treatment:

Drug: INCB186748

Part 2a: Dose Escalation combination

Experimental group

Description:

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Treatment:

Drug: GEMNabP

Drug: INCB186748

Drug: Cetuximab

Drug: mFOLFIRINOX

Part 2b: Dose Expansion combination

Experimental group

Description:

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Treatment:

Drug: GEMNabP

Drug: INCB186748

Drug: Cetuximab

Drug: mFOLFIRINOX