Study of Treatment With Sacituzumab and Zimberelimab for Patients With Lung Cancer Confined to the Chest and Previously Operated on Who Were Not Disease-free.

NCT06431633 | Recruiting Phase 3 DMC

• 2 other identifiers: GECP 23/03_ARIAN2024-512960-75-00
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 30

Brief Summary

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.

Conditions

Lung Diseases; Carcinoma, Non-Small-Cell Lung; Resectable Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  The time from random assignment to cancer recurrence or death from any cause, assessed up to 36 months

Secondary Outcomes (2)

• Overall survival

  To evaluate at 12, 24 and 36 months after the start of adjuvant treatment

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  From the subject's written consent to participate in the study through 180 days after the final administration of the drug

Other Outcomes (1)

• Change in levels of ctDNA during treatment

  To analyze at pretreatment, after 6 months of treatment, and at disease relapse, assessed up to 36 months

Study Arms (3)

ARM 1: Observation-investigator decision

ACTIVE COMPARATOR

Patients randomized in this arm will be in observation for 10 months. It is allowed to administer adjuvant treatment according to investigator criteria. Immunotherapy is not allowed in this arm, only chemotherapy treatment is allowed.

Drug: Cisplatin; Drug: Carboplatin

ARM 2: Immunotherapy. Zimberelimab treatment for 13 cycles

EXPERIMENTAL

Adjuvant treatment with Zimberelimab will start between the 3rd to the 10th week from surgery. 13 cycles will be administered in total. Cycles will be administered in 21-day intervals (Q3W). Zimberelimab: day 1 360 mg IV Q3W (13 cycles)

Drug: Zimberelimab

ARM 3: Sacituzumab Govitecan + Zimberelimab for 8 cycles + Zimberelimab for 5 cycles

EXPERIMENTAL

Sacituzumab Govitecan: day 1 and 8; 10mg/Kg IV Q3W Zimberelimab: day 1 360 mg IV Q3W Treatment sequence: Adjuvant treatment will start between the 3rd to the 10th week from surgery. 13 cycles will be administered in total. Cycles will be administered in 21-day intervals (Q3W). Patients will receive 8 cycles of Sacituzumab Govitecan + Zimberelimab and 5 cycles of Zimberelimab monotherapy.

Drug: Zimberelimab; Drug: Sacituzumab govitecan

Interventions

Zimberelimab DRUG

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.

Also known as: anti-PD-1 monoclonal antibody AB122

ARM 2: Immunotherapy. Zimberelimab treatment for 13 cycles; ARM 3: Sacituzumab Govitecan + Zimberelimab for 8 cycles + Zimberelimab for 5 cycles

Sacituzumab govitecan DRUG

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.

Also known as: Trodelvy

ARM 3: Sacituzumab Govitecan + Zimberelimab for 8 cycles + Zimberelimab for 5 cycles

Cisplatin DRUG

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.

Also known as: Platinol

ARM 1: Observation-investigator decision

Carboplatin DRUG

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

Also known as: Paraplatin

ARM 1: Observation-investigator decision

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients diagnosed of primary non-small cell lung cancer, histologically confirmed.
• \. Patients should be classified postoperatively in stage IB, IIA, IIB, IIIA or IIIB (N2) according to pathological criteria (pTNM) and according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
• \. Complete surgical resection (R0) of the primary NSCLC is also essential. Surgeons are strongly advised to dissect or obtain samples of all accessible lymph node levels, as established in the European Society of Thoracic Surgeons guide. Consequently, at the end of the surgical intervention it is recommended to have obtained samples of a minimum of 3 specific mediastinal ganglionic lobe stations (N2), one of which should include station 7, and at least one N1 station
• \. The surgical intervention may consist of a lobectomy, sleeve resection, bilobectomy or pneumonectomy, as determined by the responsible surgeon based on intraoperative findings. Patients who have had only segmentectomies or wedge resections are not considered eligible for participation in this study except if R0 resection can be confirmed.
• \. Only patients that do not achieve pathological complete response (pCR) seen in the surgical piece after neoadjuvant therapy are eligible.
• \. Preoperative (neoadjuvant) use of platinum-based chemotherapy + immunotherapy (anti PD-1) is mandatory.
• \. Preoperative, postoperative, or scheduled radiation therapy is not accepted for a later time. Patients with only N2 disease, who have to receive post-operative adjuvant radiotherapy will not be eligible.
• \. A minimum of 3 weeks must have elapsed between the surgical intervention performed for the NSCLC and the randomization. Adjuvant treatment must start between the 3rd and the 10th week from surgery.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• \. Patients aged ≥ 18 years.
• \. PDL1 value analysed locally (hospital must be able to provide this value before randomization)
• \. PET-CT and brain CT before randomization to confirm the absence of distant disease.
• \. Adequate hematologic and organ function
• All patients are notified of the investigational nature of this study and signed a written in-formed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
• For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception

You may not qualify if:

• \. Patients with a history of other malignant diseases, with the exception of the following:
• properly treated non-melanotic skin cancer
• cancer in situ treated with curative intent or other malignancies treated with curative intent and without signs of disease for a period of\> 3 years after the end of the treatment and which, in the opinion of the doctor in charge of their treatment, do not present a substantial risk of relapse of the previous malignant disease.
• T4 patients with invasion of heart, great vessels, carina, trachea, oesophagus or spine
• \. Patients with a combination of microcytic and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
• \. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of randomization.
• \. Patients that received live attenuated vaccines within 30 days prior to randomization
• \. History of a primary immunodeficiency, history of organ allogeneic transplantation, use of immunosuppressive drugs within 28 days before randomization or previous history of toxicity of severe immune mechanism (grade 3 or 4) with other immunological treatments
• \. Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol.
• \. Patients who have suffered untreated and / or uncontrolled cardiovascular disorders and / or who have symptomatic cardiac dysfunction
• \. Pregnant or breastfeeding women
• \. Patients in whom R0 resection cannot be confirmed.
• \. Patients with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• \. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (30)

Hospital General Universitario de Alicante

Alicante, Alicante, 03010, Spain

RECRUITING

Hospital General de Elche

Elche, Alicante, 03203, Spain

RECRUITING

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitari Vall d' Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clínic De Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08041, Spain

RECRUITING

Hospital Parc Taulí

Barcelona, Barcelona, 08208, Spain

RECRUITING

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital De Basurto

Bilbao, Bilbao, 48013, Spain

RECRUITING

Hospital Universitario Jerez De La Frontera

Jerez de la Frontera, Cádiz, 11407, Spain

RECRUITING

Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

RECRUITING

Hospital Universitari de Gran Canària Doctor Negrín

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

RECRUITING

Hospital Universitario de León

León, León, 24071, Spain

RECRUITING

Hospital Universitario Lucus Augusti

Lugo, Lugo, 27003, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario la Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

RECRUITING

Hospital de Son Espases

Palma de Mallorca, Mallorca, 07120, Spain

RECRUITING

Hospital Santa María Nai

Ourense, Ourense, 32005, Spain

RECRUITING

Hospital Universitari Son Llatzer

Palma de Mallorca, Palma de Mallorca, 07198, Spain

RECRUITING

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36036, Spain

RECRUITING

Hospital Universitario Salamanca

Salamanca, Salamanca, 37007, Spain

RECRUITING

Hospital Universitario Nuestra Señora La Candelaria

Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38009, Spain

RECRUITING

Hospital Virgen del Rocío

Seville, Sevilla, 41013, Spain

RECRUITING

Hospital Universitari Sant Joan de Reus

Reus, Tarragona, 43204, Spain

RECRUITING

Consorci Sanitari de Terrassa

Terrassa, Terrassa, 08227, Spain

RECRUITING

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

Hospital Universitario La Fe

Valencia, Valencia, 46026, Spain

RECRUITING

Hospital Clínico Universitario de Valladolid

Valladolid, Valladolid, 47003, Spain

RECRUITING

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Lung Diseases; Carcinoma, Non-Small-Cell Lung

Interventions

zimberelimab; sacituzumab govitecan; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Mariano Provencio, MD

  President of Fundacion GECP

  STUDY CHAIR

Central Study Contacts

Eva Pereira

CONTACT

+34 934302006; gecp@gecp.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: May 28, 2024
• Study Start: February 4, 2025
• Primary Completion (Estimated): November 30, 2031
• Study Completion (Estimated): November 30, 2031
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (30)