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

A Phase 1 Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: INCB099280; Drug: adagrasib

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Candiolo, Italy, 10060
    • Fondazione Del Piemonte Per L Oncologia Ircc Candiolo
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
  • Verona, Italy, 37124
    • Centro Ricerche Cliniche Di Verona (Crc)
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Barcelona, Spain, 08023
    • Hospital HM Nou Delfos
  • Pozuelo de Alarcon, Spain, 28223
    • Hospital Universitario Quirónsalud Madrid
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SE1 9RT
    • Guys Hospital
• United States
  • California
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
  • Colorado
    • Greeley, Colorado, United States, 80631
      • Banner MD Anderson Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research Centers McCrc Headquarters
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

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.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: INCB099280; Administered as specified in the treatment arm description; Drug: adagrasib; Administered as specified in the treatment arm description; Other Names: KRAZATI
Experimental: 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.	Drug: INCB099280; Administered as specified in the treatment arm description; Drug: adagrasib; Administered as specified in the treatment arm description; Other Names: KRAZATI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
INCB099280 and adagrasib plasma concentrations.	PK parameters will be calculated from the blood plasma concentrations of INCB099280 and adagrasib using standard noncompartmental (model independent) PK methods.	Up to 2 years
Objective response rate (ORR)	Defined as having a best overall response of complete response (CR) or partial response (PR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.	Up to 2 years
Disease Control Rate (DCR)	Defined as having a best overall response of CR, PR, or stable disease (SD) ≥ 15 weeks (from the start of treatment) assessed per RECIST v1.1 by the investigator.	Up to 2 years
Duration of Response (DOR)	Defined as the time from the first CR or PR until disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause, whichever occurs earlier.	Up to 2 years
Progression-free survival (PFS)	Defined as absence of disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause from start of treatment.	Up to 12 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: Mirati Therapeutics Inc.
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Actual): April 11, 2025
• Study Completion (Actual): July 11, 2025

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: colorectal cancer (CRC); non-small cell lung cancer (NSCLC); KRASG12C mutation
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Adagrasib
• Other Study ID Numbers: INCB99280-204; 2023-503223-26-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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