A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination with Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations
- Conditions
- Untreated metastatic NSCLCUntreated Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations1003866610029107
- Registration Number
- NL-OMON53866
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method