A Study To Evaluate INCB186748 In Participants With Advanced Or Metastatic Solid Tumors With KRAS G12D Mutation

Study Overview

A Study to Evaluate 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.

N/A

Solid Tumors

DRUG: INCB186748
DRUG: Cetuximab
DRUG: GEMNabP
DRUG: mFOLFIRINOX

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

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2025-02-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-25
First Submitted that Met QC Criteria 2025-02-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-09-02
First Posted (ESTIMATED) 2025-02-10	Results First Posted N/A	Last Verified 2025-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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 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 2a: Dose Escalation combination INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB186748 INCB186748 will be administered at protocol defined dose. 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.
EXPERIMENTAL: Part 2b: Dose Expansion combination INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB186748 INCB186748 will be administered at protocol defined dose. 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.

Primary Outcome Measures	Measure Description	Time Frame
Number of participants with Dose Limiting Toxicities (DLTs)	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)	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	Number of participants with TEAEs leading to dose modification or discontinuation.	Up to approximately 12 months and 60 days

Secondary Outcome Measures	Measure Description	Time Frame
INCB186748 pharmacokinetic (PK) in Plasma	INCB186748 concentration in plasma.	Up to approximately 12 months
Objective Response Rate (ORR)	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)	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)	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

Contacts and Locations

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

Study Contact

Name: Incyte Corporation Call Center (US)

Phone Number: 1.855.463.3463

Email: medinfo@incyte.com

Study Contact Backup

Name: Incyte Corporation Call Center (ex-US)

Phone Number: +800 00027423

Email: eumedinfo@incyte.com

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

≥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.

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.

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Incyte Medical Monitor, Incyte Corporation

Publications

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

General Publications

No publications available

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