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.

Trial Title: 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.

NCT ID: NCT06431633

Condition: Lung Diseases
Carcinoma, Non-Small-Cell Lung
Resectable Lung Non-Small Cell Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Carboplatin
Sacituzumab govitecan

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Zimberelimab
Description: 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.
Arm group label: ARM 2: Immunotherapy. Zimberelimab treatment for 13 cycles
Arm group label: ARM 3: Sacituzumab Govitecan + Zimberelimab for 8 cycles + Zimberelimab for 5 cycles

Other name: anti-PD-1 monoclonal antibody AB122

Intervention type: Drug
Intervention name: Sacituzumab govitecan
Description: 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.
Arm group label: ARM 3: Sacituzumab Govitecan + Zimberelimab for 8 cycles + Zimberelimab for 5 cycles

Other name: Trodelvy

Intervention type: Drug
Intervention name: Cisplatin
Description: 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.
Arm group label: ARM 1: Observation-investigator decision

Other name: Platinol

Intervention type: Drug
Intervention name: Carboplatin
Description: 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
Arm group label: ARM 1: Observation-investigator decision

Other name: Paraplatin

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.

Detailed description: This is an open-label, phase II, 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

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 1. Patients diagnosed of primary non-small cell lung cancer, histologically confirmed. - 2. 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 - 3. 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 - 4. 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. - 5. Only patients that do not achieve pathological complete response (pCR) seen in the surgical piece after neoadjuvant therapy are eligible. - 6. Preoperative (neoadjuvant) use of platinum-based chemotherapy + immunotherapy (anti PD-1) is mandatory. - 7. 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. - 8. 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. - 9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - 10. Patients aged ≥ 18 years. - 11. PDL1 value analysed locally (hospital must be able to provide this value before randomization) - 12. PET-CT and brain CT before randomization to confirm the absence of distant disease. - 13. Adequate hematologic and organ function - 14.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. - 15.For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception - 16. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception - 17. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs. - 18.Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug. - 19.Patient capable of proper therapeutic compliance and accessible for correct follow-up - 20. Patients with a life expectancy of at least more than 12 weeks Exclusion Criteria: - 1. 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. - 2.T4 patients with invasion of heart, great vessels, carina, trachea, oesophagus or spine - 3. Patients with ALK translocation, STK11 o KEAP1 known mutations before inclusion in this trial. - 4. Patients with adenocarcinoma NSCLC must be tested for the common EGFR mutations before inclusion. Patients with any known EGFR mutation cannot be enrolled in the study. - 5. Patients with a combination of microcytic and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma - 6. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of randomization. - 7. Patients that received live attenuated vaccines within 30 days prior to randomization - 8. 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 - 9. Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol. - 10. Patients who have suffered untreated and / or uncontrolled cardiovascular disorders and / or who have symptomatic cardiac dysfunction - 11. Pregnant or breastfeeding women - 12. Patients in whom R0 resection cannot be confirmed. - 13. 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. - 14.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. - 15. 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. - 16. History of allergy or hypersensitivity to any of the study drug components - 17. Pleural or pericardial effusion, both will be considered indicative of metastatic disease unless proven otherwise. Patients with pleural effusion not visible on chest-X-ray or too small to perform diagnostic puncture safely may be included. - 18. Have known history of HIV-1 or 2 with detectable viral load OR taking medications that may interfere with SN-38 metabolism. - 19.Severe infections within 4 weeks prior to be included in the study, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. - 20.Patients with medical, mental, neurological or psychological condition which in the opinion of the investigator would not permit the patient to understand the patient information sheet or comply with study procedures. - 21. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder; any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement; or prior pneumonectomy. - 22. Treatment with systemic immunosuppressive medications - 23.Patients with uncontrolled comorbidities that may affect the clinical trial compliance. - 24.Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Hospital General de Elche

Address:
City: Elche
Zip: 03203
Country: Spain

Contact:
Last name: Miguel Borregón Rivilla, MD

Investigator:
Last name: Miguel Borregón Rivilla, MD
Email: Principal Investigator

Facility:
Name: ICO Badalona, Hospital Germans Trias i Pujol

Address:
City: Badalona
Zip: 08916
Country: Spain

Contact:
Last name: Marta Domenech, MD

Investigator:
Last name: Marta Domenech, MD
Email: Principal Investigator

Facility:
Name: ICO Hospitalet

Address:
City: Hospitalet de Llobregat
Zip: 08908
Country: Spain

Contact:
Last name: Ernest Nadal, MD

Investigator:
Last name: Ernest Nadal, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Jerez De La Frontera

Address:
City: Jerez De La Frontera
Zip: 11407
Country: Spain

Contact:
Last name: Mª Ángeles Moreno, MD

Investigator:
Last name: Mª Ángeles Moreno, MD
Email: Principal Investigator

Facility:
Name: Hospitalario Universitario A Coruña

Address:
City: A Coruña
Zip: 15006
Country: Spain

Contact:
Last name: Rosario García Campelo, MD

Investigator:
Last name: Rosario García Campelo, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitari de Gran Canària Doctor Negrín

Address:
City: Las Palmas De Gran Canaria
Zip: 35010
Country: Spain

Contact:
Last name: David Aguiar Bujanda, MD

Investigator:
Last name: David Aguiar Bujanda
Email: Principal Investigator

Facility:
Name: Hospital Universitario Puerta de Hierro

Address:
City: Majadahonda
Zip: 28222
Country: Spain

Contact:
Last name: Mariano Provencio, MD

Investigator:
Last name: Mariano Provencio, MD
Email: Principal Investigator

Facility:
Name: Hospital de Son Espases

Address:
City: Palma De Mallorca
Zip: 07120
Country: Spain

Contact:
Last name: Aitor Azkárate Martínez, MD

Investigator:
Last name: Aitor Azkárate Martínez, MD
Email: Principal Investigator

Facility:
Name: Complejo Hospitalario Universitario de Vigo

Address:
City: Vigo
Zip: 36036
Country: Spain

Contact:
Last name: Gerardo Huidobro, MD

Investigator:
Last name: Gerardo Huidobro, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitari Sant Joan de Reus

Address:
City: Reus
Zip: 43204
Country: Spain

Contact:
Last name: Clara Lucía Gozálvez, MD

Investigator:
Last name: Clara Lucía Gozálvez, MD
Email: Principal Investigator

Facility:
Name: Hospital General Universitario de Alicante

Address:
City: Alicante
Zip: 03010
Country: Spain

Contact:
Last name: Bartomeu Massuti, MD

Investigator:
Last name: Bartomeu Massuti, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitari Vall d' Hebron

Address:
City: Barcelona
Zip: 08035
Country: Spain

Contact:
Last name: Alex Martínez, MD

Investigator:
Last name: Alex Martínez, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínic De Barcelona

Address:
City: Barcelona
Zip: 08036
Country: Spain

Contact:
Last name: Noemí Reguart

Investigator:
Last name: Noemí Reguart, MD
Email: Principal Investigator

Facility:
Name: Hospital de la Santa Creu i Sant Pau

Address:
City: Barcelona
Zip: 08041
Country: Spain

Contact:
Last name: Andres Barba, MD

Investigator:
Last name: Andres Barba, MD
Email: Principal Investigator

Facility:
Name: Hospital Parc Taulí

Address:
City: Barcelona
Zip: 08208
Country: Spain

Contact:
Last name: Laia Vilà, MD

Investigator:
Last name: Laia Vilà, MD
Email: Principal Investigator

Facility:
Name: Hospital De Basurto

Address:
City: Bilbao
Zip: 48013
Country: Spain

Contact:
Last name: Mª Ángeles Sala, MD

Investigator:
Last name: Mª Ángeles Sala, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario de León

Address:
City: León
Zip: 24071
Country: Spain

Contact:
Last name: Blanca Távara, MD

Investigator:
Last name: Blanca Távara, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Lucus Augusti

Address:
City: Lugo
Zip: 27003
Country: Spain

Contact:
Last name: Begoña Campos, MD

Investigator:
Last name: Begoña Campos, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico San Carlos

Address:
City: Madrid
Zip: 28040
Country: Spain

Contact:
Last name: Monica Antoñanzas, MD

Investigator:
Last name: Monica Antoñanzas, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Fundación Jiménez Díaz

Address:
City: Madrid
Zip: 28040
Country: Spain

Contact:
Last name: Manuel Dómine, MD

Investigator:
Last name: Manuel Dómine, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario la Paz

Address:
City: Madrid
Zip: 28046
Country: Spain

Contact:
Last name: Javier De Castro, MD

Investigator:
Last name: Javier De Castro, MD
Email: Principal Investigator

Facility:
Name: Hospital Santa María Nai

Address:
City: Ourense
Zip: 32005
Country: Spain

Contact:
Last name: Karmele Areses, MD

Investigator:
Last name: Karmele Areses
Email: Principal Investigator

Facility:
Name: Hospital Universitari Son Llatzer

Address:
City: Palma De Mallorca
Zip: 07198
Country: Spain

Contact:
Last name: Juan Coves Sarto, MD

Investigator:
Last name: Juan Coves Sarto, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Salamanca

Address:
City: Salamanca
Zip: 37007
Country: Spain

Contact:
Last name: Alejandro Olivares Hernández, MD

Investigator:
Last name: Alejandro Olivares Hernández, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Nuestra Señora La Candelaria

Address:
City: Santa Cruz De Tenerife
Zip: 38009
Country: Spain

Contact:
Last name: Karla Mercedes Medina, MD

Investigator:
Last name: Karla Mercedes Medina, MD
Email: Principal Investigator

Facility:
Name: Hospital Virgen del Rocío

Address:
City: Sevilla
Zip: 41013
Country: Spain

Contact:
Last name: Reyes Bernabé, MD

Investigator:
Last name: Reyes Bernabé, MD
Email: Principal Investigator

Facility:
Name: Consorci Sanitari de Terrassa

Address:
City: Terrassa
Zip: 08227
Country: Spain

Contact:
Last name: Remei Blanco, MD

Investigator:
Last name: Remei Blanco, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico de Valencia

Address:
City: Valencia
Zip: 46010
Country: Spain

Contact:
Last name: Amelia Insa, MD

Investigator:
Last name: Amelia Insa, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario La Fe

Address:
City: Valencia
Zip: 46026
Country: Spain

Contact:
Last name: Oscar Juan-Vidal, MD

Investigator:
Last name: Oscar Juan-Vidal, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico Universitario de Valladolid

Address:
City: Valladolid
Zip: 47003
Country: Spain

Contact:
Last name: Rafael López, MD

Investigator:
Last name: Rafael López, MD
Email: Principal Investigator

Start date: October 1, 2024

Completion date: June 15, 2031

Lead sponsor:
Agency: Fundación GECP
Agency class: Other

Source: Fundación GECP

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06431633
http://www.gecp.org