Clinical trial NCT06039384: A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation
Official title: A Phase 1 Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: KRASG12C mutation
non-small cell lung cancer (NSCLC)
colorectal cancer (CRC)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Mirati Therapeutics Inc.
First posted: 2023-09-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Part 1: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years and 90 days
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to 2 years and 90 days
Secondary outcomes:
measure: INCB099280 and adagrasib plasma concentrations.
timeFrame: Up to 2 years
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Greeley
country: United States
facility: Banner Md Anderson Cancer Center
state: Colorado
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers McCrc Headquarters
state: Texas
city: Falls Church
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L Oncologia Ircc Candiolo
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona (Crc)
city: Barcelona
country: Spain
facility: Hospital Hm Nou Delfos
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: