Open-label, phase III, randomized, stratified (PDL1- vs PDL1+), 3 arms, multicenter clinical trial. 129 resected patients (43 per arm) with stage from IB to IIIA and IIIB (N2) non-small cell lung cancer that do not achieve pathologic complete response (pCR) after neoadjuvant treatment. This clinical trial has 3 arms of treatment. ARM 1: Observation 10 months, ARM 2: treatment with immunotherapy (Zimberelimab) for 13 cycles and ARM 3: treatment with Sacituzumab Govitecan and Zimberelimab for 8 cycles and Zimberelimab monotherapy for 5 cycles. The primary objective is to evaluate the disease-free survival (DFS): defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time. Patient accrual is expected to be completed within 2 years, treatment is planned to extend during 1 years and the patients will be followed up for 2 years. The study will end once survival follow-up has concluded.
This is an open-label, phase III, randomized, stratified (PDL1- vs PDL1+), 3 arms, multicenter clinical trial. Patients stage IB to IIIA-IIIB (T3N2) after surgical resection if they did not achieve a pathological com-plete response (pCR) will be randomized 1:1:1 to: * ARM 1: Observational Arm for 10 months * ARM 2: Immunotherapy (Zimberelimab) treatment for 13 cycles, Q3W * ARM 3: Sacituzumab Govitecan + Zimberelimab Q3W for 8 cycles + Zimberelimab Q3W for 5 cycles. Patients will receive 8 cycles of the combination and 5 cycles of Zimberelimab monotherapy. The primary objective is to evaluate the disease-free survival (DFS): defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time. Disease Free survival (DFS): The time from random assignment to cancer recurrence or death from any cause. Secondary objectives: * Overall survival (OS): at 12, 24 and 36 months after the start of adjuvant treatment * Safety and tolerability of the combination of Sacituzumab Govitecan + Zimberelimab according to CTCAE v5.0. Exploratory objectives \- To evaluate whether there is a significant association between change in levels of ctDNA between baseline and after adjuvant treatment and OS and DFS. The total trial duration will be 7 years approximately. Approval-start up: 4-6 months. Patient accrual is expected to be completed within 2 years. One year of treatment and 3 years of follow up, and close-out: 4-6 months. The study will end once survival follow-up has concluded
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
129
Zimberelimab is a fully human IgG4 monoclonal antibody targeting human PD-1. PD-1 is a type I transmembrane protein that is part of the immunoglobulin gene superfamily and the CD28 family of cell surface receptors. PD-1 is an inhibitory immune checkpoint protein that is expressed on activated B cells, T cells, and myeloid cells, and it plays a key role in limiting the activity of effector T cells. Zimberelimab is formulated at 30 mg/mL in a buffer solution containing histidine/histidine-HCl buffer solution, sucrose, sodium chloride, and polysorbate 80, at pH 5.5. The investigational product is supplied as a vial contains 120 mg of active Zimberelimab at a concentration of 30mg/mL. No premedication nor profilaxis is needed before Zimberelimab administration. Zimberelimab doses are administered by IV infusion over 60 minutes, followed by a 30- to 60-minute observation period, on D1 of each 21-day cycle.
Sacituzumab govitecan (SG) is an ADC composed of the following 3 components: o The humanized monoclonal antibody hRS7 IgG1κ, which binds to Trop-2, a transmembrane calcium signal transducer that is overexpressed in many epithelial cancers. o The camptothecin-derived agent SN-38, a topoisomerase I inhibitor. o A hydrolyzable linker, with the company designation as CL2A that links the humanized monoclonal antibody to SN-38. Sacituzumab govitecan is approved globally for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) and HR+ breast cancer.
Cisplatin-based adjuvant chemotherapy Cisplatin - CAS 15663-27-1, is a platinum coordination complex with potent anti-neoplastic activity. Induces apoptosis in cancer cells, possibly via caspase-3 activation.
Cisplatin-based adjuvant chemotherapy Structure: The cis-diamino (cyclobutane-1, 1 dicarboxylate) plating. Stability: 24 hours at ambient temperature in 5% glucose, glucosamine or physiologic saline. It is recommended not to dilute with chlorinated solutions for this could affect the carboplatin. Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center. Other Name: ATC code: L01XA02
Hospital General de Elche
Elche, Alicante, Spain
NOT_YET_RECRUITINGICO Badalona, Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
NOT_YET_RECRUITINGICO Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
RECRUITINGHospital Universitario Jerez De La Frontera
Jerez de la Frontera, Cádiz, Spain
Disease free survival
Defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time.
Time frame: The time from random assignment to cancer recurrence or death from any cause, assessed up to 36 months
Overall survival
defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
Time frame: To evaluate at 12, 24 and 36 months after the start of adjuvant treatment
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.
Time frame: From the subject's written consent to participate in the study through 180 days after the final administration of the drug
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Hospitalario Universitario A Coruña
A Coruña, La Coruña, Spain
RECRUITINGHospital Universitari de Gran Canària Doctor Negrín
Las Palmas de Gran Canaria, Las Palmas, Spain
RECRUITINGHospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain
RECRUITINGHospital de Son Espases
Palma de Mallorca, Mallorca, Spain
RECRUITINGComplejo Hospitalario Universitario de Vigo
Vigo, Pontevedra, Spain
RECRUITINGHospital Universitari Sant Joan de Reus
Reus, Tarragona, Spain
RECRUITING...and 20 more locations