Olomorasib + Pembrolizumab KRAS G12C Mutant, PD-L1 TPS 1-49% Locally Advanced or Metastatic NSCLC

NCT07639242 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LCCC2518
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial evaluates the combination of olomorasib and pembrolizumab as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has a Kirsten Rat Sarcoma Virus (KRAS) G12C mutation and a programmed death-ligand (PD-L1) score between 1% and 49%. The main goal of the study is to determine how long patients live without their cancer worsening after starting treatment, also known as progression-free survival (PFS). Additional goals include evaluating how many patients experience tumor shrinkage or disappearance, how long responses to treatment last, overall survival, and the safety and side effects of the treatment combination. Furthermore, how well the treatment works in patients whose cancer has spread to the brain, outcomes in patients with a lower Eastern Cooperative Oncology Group performance status (ECOG), and whether certain tumor or blood-based biomarkers are associated with treatment response or side effects, if enough patient data is available for analysis.

Conditions

Lung Cancer; Lung Cancer (NSCLC); Metastatic NSCLC - Non-Small Cell Lung Cancer; Locally Advanced NSCLC

Keywords

olomorasib; pembrolizumab; KRAS G12C+mutant; Kirsten Rat Sarcoma Virus G12C+ mutant; programmed death-ligand; PD-L1

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS will be as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RECIST indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 5 years

Secondary Outcomes (4)

• Overall Survival(OS)

  Up to 5 years

• Adverse events (AEs) will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  Up to 5 years

• Overall response rate

  Up to 5 years

• Duration of Response (DoR)

  Up to 5 years

Study Arms (1)

Lung Cancer

EXPERIMENTAL

Drug: Olomorasib; Drug: Pembrolizumab

Interventions

Olomorasib DRUG

Olomorasib 100 mg tb, twice a day

Lung Cancer

Pembrolizumab DRUG

200 mg, 30-minute IV infusion in every 3 weeks for first 12 cycles or 395 mg for first 12 cycles Sub-cutaneous in abdomen or thigh

Lung Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to participate in this study a subject must meet ALL of the eligibility criteria outlined below.
• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Subject is willing and able to comply with study procedures based on the judgement of the investigator.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group performance status (ECOG) of 0-2
• Subjects must have previously untreated, Stage IIIB-IIIC or Stage IV Non-Small Cell Lung Cancer (NSCLC) not amenable to curative intent treatment.
• Measurable disease according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1 within 28 days prior to treatment
• Known KRAS G12C mutation identified on tumor tissue or circulating tumor DNA (ctDNA) as determined by molecular testing performed in a CLIA, CAP or other similarly certified laboratory per local guidelines.
• Subjects must have a known PD-L1 tumor proportion score (TPS) of 1-49% as determined by an IHC assay in a CLIA, CAP, or other similarly certified laboratory as per local guidelines

You may not qualify if:

• Subject has a serious pre-existing medical condition(s) that, in the judgment of the Investigator, would preclude participation in this study, including interstitial lung disease (ILD) or severe dyspnea at rest and uncontrolled disease-related pericardial effusion or pleural effusion.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Shetal A Patel, MD, PhD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose M Hall

CONTACT

919-984-0000; rose_hall@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2026
• First Posted: June 10, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 21, 2030
• Study Completion (Estimated): June 21, 2030
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)