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.

Last updated: April 8, 2025
Sponsor: Fundación GECP
Overall Status: Active - Recruiting

Phase

3

Condition

Carcinoma

Treatment

Zimberelimab

Cisplatin

Carboplatin

Clinical Study ID

NCT06431633
GECP 23/03_ARIAN
2024-512960-75-00
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patients diagnosed of primary non-small cell lung cancer, histologicallyconfirmed.
  1. Patients should be classified postoperatively in stage IB, IIA, IIB, IIIA orIIIB (N2) according to pathological criteria (pTNM) and according to 8thversion of the International Association for the Study of Lung Cancer StagingManual in Thoracic Oncology
  1. Complete surgical resection (R0) of the primary NSCLC is also essential.Surgeons are strongly advised to dissect or obtain samples of all accessiblelymph node levels, as established in the European Society of Thoracic Surgeonsguide. Consequently, at the end of the surgical intervention it is recommendedto have obtained samples of a minimum of 3 specific mediastinal ganglionic lobestations (N2), one of which should include station 7, and at least one N1station
  1. The surgical intervention may consist of a lobectomy, sleeve resection,bilobectomy or pneumonectomy, as determined by the responsible surgeon based onintraoperative findings. Patients who have had only segmentectomies or wedgeresections are not considered eligible for participation in this study exceptif R0 resection can be confirmed.
  1. Only patients that do not achieve pathological complete response (pCR) seen inthe surgical piece after neoadjuvant therapy are eligible.
  1. Preoperative (neoadjuvant) use of platinum-based chemotherapy + immunotherapy (anti PD-1) is mandatory.
  1. Preoperative, postoperative, or scheduled radiation therapy is not accepted fora later time. Patients with only N2 disease, who have to receive post-operativeadjuvant radiotherapy will not be eligible.
  1. A minimum of 3 weeks must have elapsed between the surgical interventionperformed for the NSCLC and the randomization. Adjuvant treatment must startbetween the 3rd and the 10th week from surgery.
  1. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  1. Patients aged ≥ 18 years.
  1. PDL1 value analysed locally (hospital must be able to provide this value beforerandomization)
  1. PET-CT and brain CT before randomization to confirm the absence of distantdisease.
  1. Adequate hematologic and organ function
  • 14.All patients are notified of the investigational nature of this study and signeda written in-formed consent in accordance with institutional and nationalguidelines, including the Declaration of Helsinki prior to any trial-relatedintervention.

  • 15.For female patients of childbearing potential, agreement (by patient and/orpartner) to use a highly effective form(s) of contraception

  1. For male patients with female partners of childbearing potential, agreement (bypatient and/or partner) to use a highly effective form(s) of contraception
  1. Oral contraception should always be combined with an additional contraceptivemethod because of a potential interaction with the study drugs.
  • 18.Women who are not postmenopausal or surgically sterile must have a negative serumpregnancy test result within 14 days prior to initiation of study drug.

  • 19.Patient capable of proper therapeutic compliance and accessible for correctfollow-up

  1. Patients with a life expectancy of at least more than 12 weeks

Exclusion

Exclusion Criteria:

  1. Patients with a history of other malignant diseases, with the exception of thefollowing:
  • properly treated non-melanotic skin cancer

  • cancer in situ treated with curative intent or other malignancies treated withcurative intent and without signs of disease for a period of> 3 years after theend of the treatment and which, in the opinion of the doctor in charge of theirtreatment, do not present a substantial risk of relapse of the previousmalignant disease.

  • 2.T4 patients with invasion of heart, great vessels, carina, trachea, oesophagus orspine

  1. Patients with ALK translocation, STK11 o KEAP1 known mutations before inclusionin this trial.
  1. Patients with adenocarcinoma NSCLC must be tested for the common EGFR mutationsbefore inclusion. Patients with any known EGFR mutation cannot be enrolled inthe study.
  1. Patients with a combination of microcytic and non-small cell lung cancer, acarcinoid lung tumor or large cell neuroendocrine carcinoma
  1. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn'sdisease) or GI perforation within 6 months of randomization.
  1. Patients that received live attenuated vaccines within 30 days prior torandomization
  1. History of a primary immunodeficiency, history of organ allogeneictransplantation, use of immunosuppressive drugs within 28 days beforerandomization or previous history of toxicity of severe immune mechanism (grade 3 or 4) with other immunological treatments
  1. Patients with active or uncontrolled infections or with serious medicalconditions or disorders that may not allow patient management as established inthe protocol.
  1. Patients who have suffered untreated and / or uncontrolled cardiovasculardisorders and / or who have symptomatic cardiac dysfunction
  1. Pregnant or breastfeeding women
  1. Patients in whom R0 resection cannot be confirmed.
  1. Patients with an active, known or suspected autoimmune disease. Participantswith type I diabetes mellitus, hypothyroidism only requiring hormonereplacement, skin disorders not requiring systemic treatment, or conditions notexpected to recur in the absence of an external trigger are permitted toenroll.
  • 14.Patients with a condition requiring systemic treatment with eithercorticosteroids or other immunosuppressive medications within 14 days ofrandomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmunedisease.

  1. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patientswith a history of HBV or HCV, patients with detectable viral loads will beexcluded.
  1. History of allergy or hypersensitivity to any of the study drug components
  1. Pleural or pericardial effusion, both will be considered indicative ofmetastatic disease unless proven otherwise. Patients with pleural effusion notvisible on chest-X-ray or too small to perform diagnostic puncture safely maybe included.
  1. Have known history of HIV-1 or 2 with detectable viral load OR takingmedications that may interfere with SN-38 metabolism.
  • 19.Severe infections within 4 weeks prior to be included in the study, including butnot limited to hospitalization for complications of infection, bacteraemia, orsevere pneumonia.

  • 20.Patients with medical, mental, neurological or psychological condition which inthe opinion of the investigator would not permit the patient to understand thepatient information sheet or comply with study procedures.

  1. Clinically severe pulmonary compromise resulting from intercurrent pulmonaryillnesses including, but not limited to, any underlying pulmonary disorder; anyautoimmune, connective tissue, or inflammatory disorders with pulmonaryinvolvement; or prior pneumonectomy.
  1. Treatment with systemic immunosuppressive medications
  • 23.Patients with uncontrolled comorbidities that may affect the clinical trialcompliance.

  • 24.Sexually active men and women of childbearing potential who are not willing touse an effective contraceptive method during the study.

Study Design

Total Participants: 129
Treatment Group(s): 4
Primary Treatment: Zimberelimab
Phase: 3
Study Start date:
February 04, 2025
Estimated Completion Date:
November 30, 2031

Study Description

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

Connect with a study center

  • Hospital General de Elche

    Elche, Alicante 03203
    Spain

    Site Not Available

  • ICO Badalona, Hospital Germans Trias i Pujol

    Badalona, Barcelona 08916
    Spain

    Site Not Available

  • ICO Hospitalet

    Hospitalet de Llobregat, Barcelona 08908
    Spain

    Active - Recruiting

  • Hospital Universitario Jerez De La Frontera

    Jerez De La Frontera, Cádiz 11407
    Spain

    Active - Recruiting

  • Hospitalario Universitario A Coruña

    A Coruña, La Coruña 15006
    Spain

    Active - Recruiting

  • Hospital Universitari de Gran Canària Doctor Negrín

    Las Palmas De Gran Canaria, Las Palmas 35010
    Spain

    Active - Recruiting

  • Hospital Universitario Puerta de Hierro

    Majadahonda, Madrid 28222
    Spain

    Active - Recruiting

  • Hospital de Son Espases

    Palma De Mallorca, Mallorca 07120
    Spain

    Active - Recruiting

  • Complejo Hospitalario Universitario de Vigo

    Vigo, Pontevedra 36036
    Spain

    Active - Recruiting

  • Hospital Universitari Sant Joan de Reus

    Reus, Tarragona 43204
    Spain

    Active - Recruiting

  • Hospital General Universitario de Alicante

    Alicante, 03010
    Spain

    Active - Recruiting

  • Hospital Clínic De Barcelona

    Barcelona, 08036
    Spain

    Active - Recruiting

  • Hospital Parc Taulí

    Barcelona, 08208
    Spain

    Active - Recruiting

  • Hospital Universitari Vall d' Hebron

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041
    Spain

    Active - Recruiting

  • Hospital De Basurto

    Bilbao, 48013
    Spain

    Active - Recruiting

  • Hospital Universitario de León

    León, 24071
    Spain

    Active - Recruiting

  • Hospital Universitario Lucus Augusti

    Lugo, 27003
    Spain

    Active - Recruiting

  • Hospital Clínico San Carlos

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario la Paz

    Madrid, 28046
    Spain

    Site Not Available

  • Hospital Santa María Nai

    Ourense, 32005
    Spain

    Active - Recruiting

  • Hospital Universitari Son Llatzer

    Palma De Mallorca, 07198
    Spain

    Active - Recruiting

  • Hospital Universitario Salamanca

    Salamanca, 37007
    Spain

    Active - Recruiting

  • Hospital Universitario Nuestra Señora La Candelaria

    Santa Cruz De Tenerife, 38009
    Spain

    Active - Recruiting

  • Hospital Virgen del Rocío

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Consorci Sanitari de Terrassa

    Terrassa, 08227
    Spain

    Active - Recruiting

  • Hospital Clínico de Valencia

    Valencia, 46010
    Spain

    Active - Recruiting

  • Hospital Universitario La Fe

    Valencia, 46026
    Spain

    Active - Recruiting

  • Hospital Clínico Universitario de Valladolid

    Valladolid, 47003
    Spain

    Active - Recruiting

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