Metastatic Non–Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Members of all genders, races, and ethnic groups are eligible for this study. Participants must meet all the following inclusion 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 for participants with nonsquamous NSCLC tumor histology if status is unknown 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. 6)Have not received prior systemic treatment for metastatic NSCLC. Participants who received chemotherapy for nonmetastatic diseases are eligible if the treatment was completed at least 12 months prior to the start of study treatment. 7)Measurable disease per CT or MRI 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). 11)Willing and able to comply with the requirements and restrictions in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
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 participant 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 (> 10mg/day prednisone equivalent). Use of topical, inhalational, intranasal, and intraocular 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)Meet any of the following criteria for cardiac disease: a)Myocardial infarction or unstable angina pectoris within 6 months prior to 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 prior to enrollment. 13)Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 14)Has received radiotherapy within 2 weeks prior to first dose of study intervention or radio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of domvanalimab (DOM) + Zimberelimab (ZIM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy (Group A versus Group B) on: •Progression-free survival (PFS) according to Response Evaluation Criterai in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR) •Overall survival (OS) ;Secondary Objective: •To compare the effect of DOM+ZIM in combination with chemotherapy relative to PEMBRO in combination with chemotherapy (Group A vs Group B) on overall response rate (ORR) as assessed by BICR according to RECIST v1.1 •To evaluate duration of response (DOR) as assessed by BICR according to the RECIST v1.1 •To evaluate the safety and tolerability of DOM+ZIM in combination with chemotherapy versus PEMBRO in combination with chemotherapy (Group A vs Group B) •To compare the effect of DOM+ZIM in combination with chemotherapy relative to PEMBRO in combination with chemotherapy (Group A vs Group B) on health-related quality of life (QOL) using non–small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ). ;Primary end point(s): •Primary endpoints of the study are PFS as assessed by BICR and OS ;Timepoint(s) of evaluation of this end point: The first interim analysis of OS will be conducted at the same time as the primary analysis of PFS when approximately 384 disease progression events as assessed by BICR or deaths have occurred among Groups A and B. The second interim analysis of OS will be conducted when approximately 357 deaths (80% of IF) have occurred in the Groups A and B. The final analysis of OS is projected to be conducted around 58 months after the first participant is randomized when approximately 446 deaths have occurred in Groups A and B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints are ORR as assessed by BICR and time to first symptom deterioration in NSCLC SAQ total score.;Timepoint(s) of evaluation of this end point: •Time to first symptom deterioration in NSCLC-SAQ total score. | — |
Countries
Argentina, Austria, Belgium, Chile, Germany, Italy, Korea, Democratic People's Republic of, Netherlands, Portugal, Singapore, Spain, Taiwan
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed