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

A Phase 1, Open-Label, Multicenter Study of 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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: INCA33890; Drug: INCB161734; Drug: Cetuximab; Drug: Retifanlimab; Drug: GEMNabP; Drug: mFOLFIRINOX; Drug: FOLFIRI; Drug: FOLFOX

• Study Type: Interventional
• Enrollment (Estimated): 710
• Phase: Phase 1

Contacts and Locations

• 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

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 02050
      • Recruiting
      • Chris OBrien Lifehouse
    • Darlinghurst, New South Wales, Australia, 02010
      • Recruiting
      • St Vincent's Hospital Sydney
  • Victoria
    • Melbourne, Victoria, Australia, 03004
      • Recruiting
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 03000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 06009
      • Recruiting
      • Linear Clinical Research
• Belgium
  • Brussels, Belgium, 01200
    • Recruiting
    • Cliniques Universitaires Ucl Saint-Luc
  • Edegem, Belgium, 02650
    • Recruiting
    • Universitair Ziekenhuis Antwerpen (UZA)
  • Leuven, Belgium, 03000
    • Recruiting
    • Universitair Ziekenhuis (Uz) Leuven
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital Cancer Center
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Center
• France
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
  • Toulouse, France, 31059
    • Recruiting
    • Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Rozzano, Italy, 20089
    • Recruiting
    • IRCCS Istituto Clinico Humanitas
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche di Verona
• Japan
  • Chiba, Japan, 277-0882
    • Recruiting
    • National Cancer Center Hospital East
  • Tokyo, Japan, 135-0063
    • Recruiting
    • The Cancer Institute Hospital of JFCR
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital General Universitario Vall D Hebron
  • Madrid, Spain, 28040
    • Recruiting
    • Fundación Jiménez Díaz
  • Madrid, Spain, 28223
    • Completed
    • Hospital Universitario Quironsalud Madrid
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Hospital
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Healthcare Hematology-Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institue At Healthone
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Withdrawn
      • Mayo Clinic Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Withdrawn
      • Florida Cancer Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Withdrawn
      • Mayo Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medicine
    • New York, New York, United States, 10022
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Jefferson University Hospitals
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years old.
• Locally advanced or metastatic solid tumor with KRAS G12D mutation.
• For Part 1a and Part 2 Combination Groups 1, 2, and 7: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, declined available therapies that are known to confer clinical benefit, or no standard available treatment to improve the disease outcome.
• Cohort specific requirements aas defined in the protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

• 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

Other protocol-defined Inclusion/Exclusion Criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

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: INCA33890; INCA33890 will be administered at protocol defined dose.; 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.; Drug: FOLFIRI; FOLFIRI will be administered at protocol defined dose.; Drug: FOLFOX; FOLFOX 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: INCA33890; INCA33890 will be administered at protocol defined dose.; 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.; Drug: FOLFIRI; FOLFIRI will be administered at protocol defined dose.; Drug: FOLFOX; FOLFOX 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 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
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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 20, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer (CRC); non-small cell lung cancer (NSCLC); INCB161734; KRASG12D Mutation; pancreatic ductal adenocarcinoma (PDAC)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab; Folfox protocol; IFL protocol
• Other Study ID Numbers: INCB161734-101; 2023-507091-47-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No