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

Incyte

Status and phase: Active, not recruiting; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: adagrasib; Drug: INCB099280

Study type: Interventional

Funder types: Industry

Identifiers

NCT06039384

2023-503223-26-00 (Registry Identifier)

INCB99280-204

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Part 1: Dose Finding

Experimental group

Description:

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.

Treatment:

Drug: INCB099280

Drug: adagrasib

Part 2: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: INCB099280

Drug: adagrasib