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

NCT ID: NCT06818812

Last Updated: 2025-09-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-27

Study Completion Date

2027-03-27

Brief Summary

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

Detailed Description

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Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1a: Dose Escalation monotherapy

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Part 1b: Dose Expansion monotherapy

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Part 1c: Pharmacodynamic cohort

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Part 1d: Food-Effect

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Part 2a: Dose Escalation combination

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Cetuximab

Intervention Type DRUG

Cetuximab will be administered at protocol defined dose.

GEMNabP

Intervention Type DRUG

GEMNabP will be administered at protocol defined dose.

mFOLFIRINOX

Intervention Type DRUG

mFOLFIRINOX will be administered at protocol defined dose.

Part 2b: Dose Expansion combination

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

Group Type EXPERIMENTAL

INCB186748

Intervention Type DRUG

INCB186748 will be administered at protocol defined dose.

Cetuximab

Intervention Type DRUG

Cetuximab will be administered at protocol defined dose.

GEMNabP

Intervention Type DRUG

GEMNabP will be administered at protocol defined dose.

mFOLFIRINOX

Intervention Type DRUG

mFOLFIRINOX will be administered at protocol defined dose.

Interventions

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INCB186748

INCB186748 will be administered at protocol defined dose.

Intervention Type DRUG

Cetuximab

Cetuximab will be administered at protocol defined dose.

Intervention Type DRUG

GEMNabP

GEMNabP will be administered at protocol defined dose.

Intervention Type DRUG

mFOLFIRINOX

mFOLFIRINOX will be administered at protocol defined dose.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Incyte Medical Monitor

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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UCLA Healthcare Hematology-Oncology

Santa Monica, California, United States

Site Status

Sarah Cannon Research Institue At Healthone

Denver, Colorado, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Baltimore, Maryland, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Jefferson University Hospitals

Philadelphia, Pennsylvania, United States

Site Status

Scri Oncology Partners

Nashville, Tennessee, United States

Site Status

Md Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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2024-519018-30-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

INCB186748-101

Identifier Type: -

Identifier Source: org_study_id

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