Untreated metastatic NSCLC
Conditions
Interventions
• Group A (ZIM+DOM + chemotherapy):
Approximately 320 participants will be randomized to Group A to receive ZIM 360
mg by IV infusion plus DOM 1200 mg by IV infusion with platinum doublet
chemother
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Members of all genders, races, and ethnic groups are eligible for this study. Participants must meet all the following eligibility criteria to be eligible for participation in this study (no waivers for participant eligibility will be permitted). 1) Participants assigned male at birth and participants assigned female at birth, 18 years of age or older, able to understand and give written informed consent. 2) Life expectancy >= 3 months. 3) Pathologically documented NSCLC that meets both criteria below: a) Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on AJCC, Eighth Edition). b) Have documented negative test results for EGFR and ALK mutations. Note: Tumor testing for EGFR or ALK mutations is required for participants with nonsquamous NSLC tumor histology if status is unknown (Section 6.3.9). 4) Have no actionable genomic alterations such as ROS proto-oncogene 1, neurotrophic tyrosine receptor kinase, proto-oncogene B-raf, RET mutations, or other driver oncogenes with approved frontline therapies. Testing of actionable genomic alterations required by local regulations will be performed locally. 5) Provide adequate tumor tissue from locations not radiated prior to biopsy to evaluate PD L1 expression prior to randomization. Bone biopsies, cytology, and fine needle aspirates are not suitable tissues. If no tissue is available, a new biopsy will need to be obtained prior to enrollment in the study. 6) Have not received prior systemic treatment for metastatic NSCLC. Participants who received chemotherapy for nonmetastatic disease are eligible if the therapy was completed at least 12 months prior to the start of study treatment. 7) Measurable disease as per RECIST v1.1 criteria by investigator assessment. 8) ECOG performance status score of 0 or 1. 9) Organ function requirement. 10) Participants assigned male at birth and participants assigned female at birth of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception from screening visit until 6 months after the last dose of chemotherapy and 120 days after the last dose of DOM, ZIM, or PEMBRO (or longer according to local regulatory requirements), as described in Appendix 4 of the study protocol. 11) Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion criteria
Exclusion criteria: Participants who meet any of the following exclusion criteria at screening/Day -1 are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted): 1) Have mixed SCLC and NSCLC histology. 2) Positive serum pregnancy test or participants who are breastfeeding or have plans to breastfeed during the study period and for the required duration of contraception use after the last dose of study drug. 3) Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint. Participants who received PD-(L)1 inhibitors as a part of treatment for early or locally advanced stage NSCLC are not eligible. 4) Known hypersensitivity to the study drug, its metabolites, or formulation excipient. 5) Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.3. 6) Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment. Participants with a history of malignancy that has been completely treated, with no evidence of active cancer for at least 3 years prior to enrollment, or with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll. 7) Have an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. 8) Are receiving chronic systemic steroids (> 10 mg/day prednisone equivalent). Use of topical, inhalational, intra nasal, and intra ocular steroids will be permitted. 9) Have significant third-space fluid retention (eg, ascites or pleural effusion) and is not amenable for required repeated drainage 10) Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases and are not requiring use of steroids for at least 14 days prior to the start of study treatment. All participants with carcinomatous meningitis are excluded regardless of clinical stability. 11) Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). c) New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction less than 40%. 12) Active chronic inflammatory bowel disease (ulcerative colitis, Crohn*s disease) or gastrointestinal perforation within 6 months of enrollment. 13) Has a history of (noninfectious) pneumonitis/inter
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • PFS is defined as the time from the date of randomization until disease progression (PD) as assessed by BICR according to RECIST v1.1 or death from any cause, whichever comes first. • OS is defined as the time from the date of randomization to the date of death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| • ORR is defined as the proportion of participants who have achieved a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later as assessed by BICR according to RECIST v1.1. • DOR is defined as the time from the first response (CR or PR), to the first documented PD as assessed by BICR according to RECIST v1.1 or death from any cause, whichever comes first. • Incidence, severity, seriousness, and relatedness of treatment-emergent adverse events (TEAEs) and incidence and severity of clinical laboratory abnormalities. • Time to first symptom deterioration in NSCLC SAQ total score. NSCLC-SAQ Total Score is the sum all 5 domain scores (cough, pain, dyspnea, fatigue, and appetite). | — |
Countries
Netherlands
Outcome results
None listed