Título: Estudio en fase III, aleatorizado y abierto para evaluar zimberelimab y domvanalimab en combinación con quimioterapia frente a pembrolizumab con quimioterapia, como tratamiento de primera línea de pacientes con cáncer de pulmón no microcítico metastásico sin aberraciones tumorales genómicas del receptor del factor de crecimiento epidérmico ni de la quinasa del linfoma anaplásico

Especialidad: Oncología

Código de protocolo: GS-US-626-6216

Número EudraCT: 2022-000578-25

Promotor: Gilead Sciences, Inc.

Investigador principal: Dr. Vicente Guillem

Más información:

CRO: PPD

Criterios de inclusión: 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).
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 of the study protocol.
Willing and able to comply with the requirements and restrictions in this protocol
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.
Life expectancy 3 months
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 NSCLC tumor histology if status is unknown
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.
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.
Have not received prior systemic treatment for metastatic NSCLC. Participants who received chemotherapy for nonmetastatic disease are eligible if the treatment was completed at least 12 months prior to the start of study treatment.
Measurable disease per RECIST v1.1 criteria by investigator assessment Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
ECOG performance status score of 0 or 1.

Criterios de exclusión: 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): Have mixed SCLC and NSCLC histology.
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 notrequiring 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.
Meet 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%.
Active chronic inflammatory bowel disease (ulcerative colitis, Crohns disease) or gastrointestinal perforation within 6 months of enrollment.
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has received radiotherapy within 2 weeks prior to first dose of study intervention or radiotherapy to the lung that is > 30 Gy within 6 months of the first study treatment.
Has had an allogenic tissue/solid organ transplant.
Have received a live virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
Have active infection requiring treatment (eg, antibiotics).
Have known history of HIV-1 or 2 with uncontrolled viral load (ie, 200 copies/mL or CD4+ T-cell count < 350 cells/L), or taking medications that may interfere with metabolism of study drugs. No HIV testing is required unless mandated by local health authority.
Have known acute hepatitis B, known chronic hepatitis B infection with active untreated disease, or known active hepatitis C infection. In participants with a history of hepatitis B virus or hepatitis C virus, participants with detectable viral loads will be excluded. No hepatitis testing is required unless mandated by local health authority.
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
Have other concurrent medical or psychiatric conditions that, in the investigators opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
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.
Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.3 of the protocol
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.
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.
Are receiving chronic systemic steroids (> 10 mg/day prednisone equivalent). Use of topical, inhalational, intranasal, and intraocular steroids will be permitted.
Have significant third-space fluid retention (eg, ascites or pleural effusion) and is not amenable for required repeated drainage.

Fecha de firma: 17/01/2023

Estado: en marcha

Centro: Vithas Valencia 9 de Octubre