A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

NCT ID: NCT06039384

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-28
• Study Completion Date: 2025-07-11

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of INCB099280 in combination with adagrasib and to establish the MTD or identify RDE(s) for the combination of INCB099280 and adagrasib.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Finding

INCB099280 administered in combination with adagrasib in participants with previously treated KRAS glutamine to cysteine mutation at codon 12 (KRASG12C) mutant advanced solid tumors, will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.

Group Type: EXPERIMENTAL

INCB099280

Intervention Type: DRUG

Administered as specified in the treatment arm description

adagrasib

Intervention Type: DRUG

Administered as specified in the treatment arm description

Part 2: Dose Expansion

Up to 80 participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort A: previously treated KRASG12C mutated non-small cell lung cancer (NSCLC) Cohort B: previously treated KRASG12C-mutated colorectal cancer (CRC). Up to 3 doses may be selected from Part 1: Dose Finding for the Part 2: Dose Expansion.

Group Type: EXPERIMENTAL

INCB099280

Intervention Type: DRUG

Administered as specified in the treatment arm description

adagrasib

Intervention Type: DRUG

Administered as specified in the treatment arm description

Interventions

INCB099280

Administered as specified in the treatment arm description

Intervention Type: DRUG

adagrasib

Administered as specified in the treatment arm description

Intervention Type: DRUG

Other Intervention Names

KRAZATI

Eligibility Criteria

Inclusion Criteria

• KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA.
• Histologically confirmed malignant solid tumor with locally advanced and/or metastatic disease.

• Only participants with NSCLC will be enrolled into Part 2 Cohort A.
• Only participants with CRC will be enrolled into Part 2 Cohort B.
• Part 1: Disease progression on or after at least 1 prior systemic treatment.
• Part 2 (Cohort A - NSCLC): Received an anti-PD-(L)1-containing regimen and platinum based chemotherapy regimen either concurrently or sequentially
• Part 2 (Cohort B - CRC): Received at least 1 line of systemic therapy that includes the combination of fluoropyrimidine-based chemotherapy (in combination with oxaliplatin and/or irinotecan) and either a vascular endothelial growth factor-targeting monoclonal antibody or an anti-epidermal growth factor receptor monoclonal antibody (if RAS wild type). Participants with MSI-H/dMMR CRC must also have received a prior immune checkpoint inhibitor approved for this indication.
• Measurable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Estimated life expectancy > 3 months.
• Willingness to avoid pregnancy.

Exclusion Criteria

• Known additional malignancy that is progressing or requires active treatment.
• Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease.
• Part 2 only: Prior treatment with an approved or investigational agent targeting KRASG12C.
• Toxicity from prior therapy that has not recovered to protocol-defined limits.
• Received thoracic radiation of > 30 Gy within 6 months of the first dose of study treatment.
• Participation in another interventional clinical study.
• History or evidence of interstitial lung disease, including noninfectious pneumonitis.
• Presence of gastrointestinal condition that may affect drug absorption.
• Active autoimmune disease requiring systemic treatment, including corticosteroids exceeding a daily dose of 10 mg of prednisone or equivalent.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy exceeding a daily dose of 10 mg of prednisone or equivalent.
• Active infection requiring systemic therapy.
• History of organ transplantation, including allogeneic stem cell transplantation.
• Receipt of systemic antibiotics within 28 days of the first dose of study treatment.
• Probiotic usage is prohibited during screening and throughout the study treatment period.
• Received a live vaccine within 28 days of the planned start of study drug.
• Laboratory values outside the Protocol-defined ranges.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Incyte Medical Monitor

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Valkyrie Clinical Trials

Los Angeles, California, United States

Banner Md Anderson Cancer Center

Greeley, Colorado, United States

Henry Ford Health System

Detroit, Michigan, United States

Mary Crowley Cancer Research Centers McCrc Headquarters

Dallas, Texas, United States

Inova Schar Cancer Institute

Falls Church, Virginia, United States

Fondazione Del Piemonte Per L Oncologia Ircc Candiolo

Candiolo, , Italy

Irccs Istituto Clinico Humanitas

Rozzano, , Italy

Centro Ricerche Cliniche Di Verona (Crc)

Verona, , Italy

Hospital Hm Nou Delfos

Barcelona, , Spain

Hospital General Universitario Vall D Hebron

Barcelona, , Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Guys Hospital

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Countries

United States; Italy; Spain; United Kingdom

Other Identifiers

2023-503223-26-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

INCB99280-204

Identifier Type: -

Identifier Source: org_study_id