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

Phase 2Not Yet RecruitingNCT07639242

UNC Lineberger Comprehensive Cancer Center60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lung Cancer Lung Cancer (NSCLC)Locally Advanced NSCLC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Up to 5 years

Secondary Outcomes

Overall Survival(OS)

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

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)

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).

Time frame: Up to 5 years

Overall response rate

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

Time frame: Up to 5 years

Duration of Response (DoR)

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.

Time frame: Up to 5 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts