A Study To Evaluate INCB161734 In Participants With Advanced Or Metastatic Solid Tumors With KRAS G12D Mutation

Study Overview

A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

This study is conducted to determine the safety and tolerability of INCB161734 as a single agent or in combination with other anticancer therapies.

N/A

Solid Tumors

DRUG: INCB161734
DRUG: Cetuximab
DRUG: Retifanlimab
DRUG: GEMNabP
DRUG: mFOLFIRINOX

INCB161734-101
2023-507091-47-00 (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 2023-12-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-07-02
First Submitted that Met QC Criteria 2023-12-20	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-07-04
First Posted (ACTUAL) 2023-12-21	Results First Posted N/A	Last Verified 2025-07

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 INCB161734 at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB161734 INCB161734 will be administered at protocol defined dose.
EXPERIMENTAL: Part 1b: Dose Expansion monotherapy INCB161734 at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB161734 INCB161734 will be administered at protocol defined dose.
EXPERIMENTAL: Part 1c: Pharmacodynamic cohort INCB161734 at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB161734 INCB161734 will be administered at protocol defined dose.
EXPERIMENTAL: Part 2a: Dose Escalation combination INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB161734 INCB161734 will be administered at protocol defined dose. DRUG: Cetuximab Cetuximab will be administered at protocol defined dose. DRUG: Retifanlimab Retifanlimab 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 INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.	DRUG: INCB161734 INCB161734 will be administered at protocol defined dose. DRUG: Cetuximab Cetuximab will be administered at protocol defined dose. DRUG: Retifanlimab Retifanlimab 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 1d: Food-Effect Evaluate food effect on drug exposure as defined in the protocol.	DRUG: INCB161734 INCB161734 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 after first dose of study drug monotherapy and in combination with cetuximab and retifanlimab.	Up to 2 years and 90 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 2 years and 90 days

Secondary Outcome Measures	Measure Description	Time Frame
INCB161734 pharmacokinetic (PK) in Plasma	INCB161734 concentration in plasma.	Up to approximately 90 days
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 2 years
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 2 years
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 2 years

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 Groups 1 and 2: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment to improve the disease outcome
For Part 2 Combination Groups 3 and 4: 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 ≤ 2 prior standard systemic regimens for pancreatic cancer
Disease group 2: diagnosis of CRC
Disease group 3: diagnosis of NSCLC
Disease group 4: diagnosis of other advanced solid tumor and not part of Disease groups 1, 2 or 3
Part 1c: Confirmed diagnosis of PDAC, CRC, or NSCLC
Parts 2A and 2B

Combination 1: 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 2: Diagnoses of PDAC, CRC or NSCLC
Combination Group 3 (INCB161734 in combination with GEMNabP) and Combination Group 4 (INCB161734 in combination with mFOLFIRINOX):

Diagnosis of PDAC
≤ 1 prior standard systemic regimen for pancreatic cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Prior treatment with any KRAS G12D 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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Clinical Trial Record