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

NCT06039384 | Terminated Phase 1 FDA Drug

• 2 other identifiers: INCB99280-2042023-503223-26-00
• Study Type: interventional
• Target: 6
• Locations: 4 countries
• Sites: 14

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

Keywords

KRASG12C mutation; non-small cell lung cancer (NSCLC); colorectal cancer (CRC)

Outcome Measures

Primary Outcomes (3)

• Part 1: 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.

  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 Outcomes (5)

• INCB099280 and adagrasib plasma concentrations.

  Up to 2 years

• Objective response rate (ORR)

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 12 months

Study Arms (2)

Part 1: Dose Finding

EXPERIMENTAL

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.

Drug: INCB099280; Drug: adagrasib

Part 2: Dose Expansion

EXPERIMENTAL

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.

Drug: INCB099280; Drug: adagrasib

Interventions

INCB099280 DRUG

Administered as specified in the treatment arm description

Part 1: Dose Finding; Part 2: Dose Expansion

adagrasib DRUG

Administered as specified in the treatment arm description

Also known as: KRAZATI

Part 1: Dose Finding; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (14)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

Banner Md Anderson Cancer Center

Greeley, Colorado, 80631, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mary Crowley Cancer Research Centers McCrc Headquarters

Dallas, Texas, 75251, United States

Location

Inova Schar Cancer Institute

Falls Church, Virginia, 22042, United States

Location

Fondazione Del Piemonte Per L Oncologia Ircc Candiolo

Candiolo, 10060, Italy

Location

Irccs Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Centro Ricerche Cliniche Di Verona (Crc)

Verona, 37124, Italy

Location

Hospital Hm Nou Delfos

Barcelona, 08023, Spain

Location

Hospital General Universitario Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

adagrasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Incyte Medical Monitor

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: September 15, 2023
• Study Start: December 28, 2023
• Primary Completion: April 11, 2025
• Study Completion: July 11, 2025
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

US (5); GB (2); ES (4); IT (3)