Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC

Overall survival (OS)

OS is defined as the time from randomization until death from any cause.

Time frame: Up to approximately 5 years

Objective response rate (ORR)

Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by BICR.

Time frame: Up to approximately 5 years

Duration of response (DOR)

DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first. Response and progression are per RECIST v1.1, as assessed by BICR.

Time frame: Up to approximately 5 years

Incidence of adverse events (AEs)

Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5

Time frame: Up to approximately 5 years

Changes in vital signs

Number of patients with changes in vital signs.

Time frame: Up to approximately 5 years

Changes in clinical laboratory test values

Number of patients with changes in clinical laboratory test values.

Time frame: Up to approximately 5 years

Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

EORTC QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 7 single item scales (pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a 2-item global health status/quality of life scale. Change from baseline in EORTC QLQ-C30 physical functioning scale and global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden.

Time frame: Up to approximately 5 years

Time to confirmed deterioration in physical function and global health status, as measured by EORTC QLQ-C30

Time to confirmed deterioration in physical functioning subscale and overall global health status scale, as measured by EORTC QLQ-C30. Higher scores on the Higher scores on the EORTC QLQ-C30 functional scales reflect better functioning, whereas higher scores on symptom the scales reflect higher symptom burden. Time to confirmed deterioration in EORTC QLQ-C30 physical functioning subscale and overall health status scale is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.

Time frame: Up to approximately 5 years

Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ)

The NSCLC-SAQ is a participant reported outcome measure with seven items assessing key NSCLC symptoms such as: cough, pain, dyspnea, fatigue, and appetite. Change from baseline in pulmonary symptoms of cough and dyspnea will be evaluated, with higher scores indicating more severe symptoms.

Time frame: Up to approximately 5 years

Time to Confirmed Deterioration of NSCLC-related symptoms, as measured by NSCLC-SAQ

Time to confirmed deterioration in patient-reported pulmonary symptoms of cough and dypsnea, as measured by NSCLC-SAQ. Higher scores for the pulmonary symptoms on the NSCLC-SAQ indicate more severe symptoms. Time to confirmed deterioration in NSCLC-SAQ measures is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.

Time frame: Up to approximately 5 years

Concentration of zoldonrasib in Arm A

Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits.

Time frame: Up to Cycle 5 Day 1 (each cycle is 21 days)