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NCT Number: NCT07639242

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

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.

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Key information

Conditions

Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Locally Advanced NSCLC Lung Cancer (NSCLC) Lung Diseases Lung Neoplasms Metastatic NSCLC - Non-Small Cell Lung Cancer Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location contact

Rebecca Rambharose

CONTACT

[email protected]

Rose M Hall

CONTACT

[email protected]

919-984-0000

Shetal A Patel, MD, PhD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Eligibility must be maintained up until the point at which the subject receives treatment for the subject to be considered eligible for treatment.

Inclusion criteria

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

Exclusion criteria

  • 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.

Treatment and study plan

Olomorasib

Drug

Olomorasib 100 mg tb, twice a day

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

Primary outcomes

  1. Progression free survival (PFS)

    Time frame: Up to 5 years

    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.

Secondary outcomes

  1. Overall Survival(OS)

    Time frame: Up to 5 years

    OS will be defined as the time from first dose of study drug to death from any cause.

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

    Time frame: Up to 5 years

    Adverse events (AEs) will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, from the start of treatment until unacceptable toxicity leading to treatment discontinuation, treatment stopping, or completion of 2 years of treatment, whichever occurs first. The CTCAE provides a grading scale for AE severity: Grade 1 (mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated), Grade 2 (moderate; minimal, local, or noninvasive intervention indicated; limiting instrumental activities of daily living), Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living), Grade 4 (life-threatening consequences; urgent intervention required), and Grade 5 (death related to adverse event).

  3. Overall response rate

    Time frame: Up to 5 years

    Overall response rate (ORR) is defined as the proportion of response-evaluable patients who achieve a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as the disappearance of all target lesions, and PR as at least a 30% decrease in the sum of the longest diameters of target lesions. RECIST 1.1 defines stable disease (SD) as neither sufficient shrinkage for PR nor sufficient increase for progressive disease (PD), and PD as at least a 20% increase in the sum of the longest diameters of target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions

  4. Duration of Response (DoR)

    Time frame: Up to 5 years

    Duration of Response (DoR) defined as the time from a Complete Response (CR), or Partial Response (PR) to disease progression, death, or end of study. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Rose M Hall

CONTACT

[email protected]

919-984-0000

Sponsors and collaborators

Lead sponsor

UNC Lineberger Comprehensive Cancer Center

Other

Registry information

Official study title

Olomorasib Plus Pembrolizumab as First-Line Treatment for KRAS G12C Mutant, PD-L1 TPS 1-49% Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Jun 10, 2026
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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