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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06039384
• Other study ID #: INCB99280-204
• Secondary ID: 2023-503223-26-0
• Status: Recruiting
• Phase: Phase 1
• Start date: December 28, 2023
• Est. completion date: November 3, 2025

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: November 3, 2025
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• INCB099280
Administered as specified in the treatment arm description
• adagrasib
Administered as specified in the treatment arm description

Locations

Country	Name	City	State
Italy	Fondazione Del Piemonte Per L Oncologia Ircc Candiolo	Candiolo
Italy	Irccs Istituto Clinico Humanitas	Rozzano
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Hospital Hm Nou Delfos	Barcelona
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon
Spain	Hospital Universitario Virgen Macarena	Sevilla
United Kingdom	Guys Hospital	London
United Kingdom	Hammersmith Hospital	London
United States	Mary Crowley Cancer Research Centers McCrc Headquarters	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Inova Schar Cancer Institute	Falls Church	Virginia
United States	Banner Md Anderson Cancer Center	Greeley	Colorado
United States	Valkyrie Clinical Trials	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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