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

Phase 1TerminatedNCT06039384

Incyte Corporation6 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

INCB099280DRUG

Administered as specified in the treatment arm description

adagrasibDRUG

Administered as specified in the treatment arm description

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (14)

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

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting Toxicities (DLTs)

DLTs were defined as protocol-defined toxicities occurring up to and including on Day 28, except those with a clear alternative explanation. Toxicities with a clear alternative explanation (e.g., due to disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination could have been deemed non-DLTs.

Time frame: up to Day 28

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.

Time frame: up to 574 days

Number of Participants With TEAEs Leading to Treatment Interruptions, Dose Reductions, and Permanent Discontinuation of INCB099280 and Adagarsib

An AE was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.

Time frame: up to 574 days

Secondary Outcomes

Concentration of INCB099280

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered.

Data from ClinicalTrials.gov

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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

...and 4 more locations

Time frame: Lead-in Period Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, and 6

Cmax of INCB099280 When Administered Alone and in Combination With Adagrasib

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmax was defined as the maximum plasma concentration of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.