Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Study Overview
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Brief Summary
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This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation.

Official Title
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A Randomized Phase 3 Study of MRTX849 Versus Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation

Conditions
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Metastatic Non Small Cell Lung Cancer, Advanced Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: MRTX849
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation. Candidacy to receive treatment with docetaxel. Crossover Inclusion Criteria: Evidence of RECIST 1.1 defined disease progression on docetaxel per BICR ECOG performance status 0-2 Exclusion Criteria: Prior treatment with an agent targeting KRAS G12C (e.g., AMG 510, Sotorasib). Active brain metastases. Crossover Exclusion Criteria: Receipt of any other systemic anti-cancer therapy after last administration of docetaxel on the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRTX849<br> | Drug: MRTX849<br>* 21 day cycles<br>* Other names: KRAZATI;|
| Active Comparator: Docetaxel<br> | Drug: Docetaxel<br>* 21 day cycles<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Defined as time from randomization until disease progression or death from any cause, whichever occurs first. | 32 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined as time from date of randomization to date of death due to any cause. | 49 Months | 
| Objective Response Rate (ORR) | Defined as the percent of patients documented to have a confirmed CR or PR. | 32 Months | 
| Duration of Response (DOR) | Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first. | 49 Months | 
| 1-year Survival Rate |  | 49 Months | 
| Safety | characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, laboratory abnormalities, and number of patients discontinuing study treatment due to an adverse event. | 49 Months | 
| Population PK parameters of MRTX849 | Data for this Outcome Measure will not be reported here but will be used in a Population PK Analysis which will include participants who were not enrolled in this study, and issued in a separate report. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules | 49 Months | 
| Patient Reported Outcomes (PROs) | To be assessed by Lung Cancer Symptom Scale (LCSS). | 49 Months | 
| Quality of LIfe Assessment | To be assessed by European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L). | 49 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, KRAS G12C, Non-small cell lung cancer, Metastatic Cancer, Docetaxel, Phase 3 Clinical Trial, Adagrasib, KRAS, KRAZATI