This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile \[GEP\] and tumor mutational burden \[TMB\]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.
After Amendment 5, participants can receive 800 mg of favezelimab every 3 weeks (Q3W)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
245
200 mg pembrolizumab solution for intravenous (IV) infusion administered Q3W
200 mg or 800 mg favezelimab solution for IV infusion administered Q3W
20 mg lenvatinib capsules administered orally once daily
Quavonlimab solution for IV infusion administered at the RP2D (dose and schedule based on study NCT03179436)
Arizona Oncology Associates, PC- HAL ( Site 8001)
Tempe, Arizona, United States
University of California Davis Comprehensive Cancer Center ( Site 0137)
Sacramento, California, United States
University of California San Francisco ( Site 0111)
San Francisco, California, United States
UCLA Hematology/Oncology -Santa Monica ( Site 0108)
Santa Monica, California, United States
Yale University School of Medicine ( Site 0100)
New Haven, Connecticut, United States
Objective Response Rate (ORR)
ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by local site radiologic review. The percentage of participants who experience CR or PR as assessed by local site radiologic review with confirmatory assessment per RECIST 1.1 is presented. Participants were assigned to 1 of 4 biomarker-defined groups (GEP low/TMB low, GEP low/TMB high, GEP high/TMB low, and GEP high/TMB high) and randomized within-group to receive a combination treatment of study interventions. Per protocol, no participants within GEP Low/TMB Low biomarker group were assigned to receive Pembrolizumab + Favezelimab 800 mg.
Time frame: Up to approximately 80 months
Progression Free Survival (PFS)
PFS was defined as the time from allocation to the first documented progressive disease (PD) or death due to any cause, whichever occurs first according to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by local site radiologic review. PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS for all participants is presented. Participants were assigned to 1 of 4 biomarker-defined groups (GEP low/TMB low, GEP low/TMB high, GEP high/TMB low, and GEP high/TMB high) and randomized within-group to receive a combination treatment of study interventions. Per protocol, no participants within GEP Low/TMB Low biomarker group were assigned to receive Pembrolizumab + Favezelimab 800 mg.
Time frame: Up to approximately 80 months
Overall Survival (OS)
OS was defined as the time from the date of allocation to death due to any cause. The OS for all participants is presented. Participants were assigned to 1 of 4 biomarker-defined groups (GEP low/TMB low, GEP low/TMB high, GEP high/TMB low, and GEP high/TMB high) and randomized within-group to receive a combination treatment of study interventions. Per protocol, no participants within GEP Low/TMB Low biomarker group were assigned to receive Pembrolizumab + Favezelimab 800 mg.
Time frame: Up to approximately 80 months
Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants in each treatment arm experiencing an AE is reported.
Time frame: Up to approximately 80 months
Number of Participants Discontinuing Study Drug Due to AEs
An AE was defined as any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants in each treatment arm that discontinued study drug due to an AE is reported.
Time frame: Up to approximately 39 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Mayo Clinic Florida ( Site 0115)
Jacksonville, Florida, United States
University of Maryland ( Site 0136)
Baltimore, Maryland, United States
Mayo Clinic Rochester - St. Mary's Hospital ( Site 0117)
Rochester, Minnesota, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0112)
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center ( Site 0113)
New York, New York, United States
...and 71 more locations