Phase III Trial of Sacituzumab Govitecan and Zimberelimab in Resected Non-Small Cell Lung Cancer Lacking Pathological Complete Response
- Trial ID
- 2024-512960-75-00
- Protocol
- GECP 23/03
- Sponsor
- Fundacion GECP
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase III clinical trial is to evaluate **disease-free survival (DFS)** in patients with resectable non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response after neoadjuvant treatment. DFS is defined as the duration from randomization to the earliest occurrence of disease recurrence, any new lung cancer, or death from any cause. This measure is clinically relevant as it provides insight into the efficacy of the adjuvant treatment regimen in prolonging the period without disease progression, which is crucial for improving patient outcomes.
Secondary objectives include:
- Overall survival (OS) at 12, 24, and 36 months following the initiation of adjuvant treatment. This objective assesses the long-term survival benefits of the treatment.
- Safety and tolerability of the combination of **Sacituzumab Govitecan** and **Zimberelimab** according to CTCAE v5.0. This evaluation is essential to ensure that the treatment regimen is not only effective but also safe for patients.
Participants
The clinical trial involves participants diagnosed with **resectable non-small cell lung cancer**. The study population includes both male and female subjects, aged 18 years and older, with a life expectancy of at least 12 weeks. Participants are required to have undergone complete surgical resection of the primary tumor and must not have achieved a pathological complete response after neoadjuvant therapy. The trial does not include vulnerable populations. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on specific inclusion criteria, including adequate hematologic and organ function, and the absence of distant disease confirmed by PET-CT and brain CT. Lifestyle considerations such as the use of contraception are required for participants of childbearing potential. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **Zimberelimab** and **Sacituzumab Govitecan** as adjuvant treatments for patients with resectable non-small cell lung cancer (NSCLC) who have not achieved a pathological complete response following neoadjuvant therapy. This is a phase III, randomized, double-blind, controlled trial. The primary objective is to assess disease-free survival (DFS), defined as the time from randomization to the earliest event of disease recurrence, new lung cancer, or death from any cause. Secondary endpoints include overall survival at 12, 24, and 36 months, as well as the safety and tolerability of the drug combination according to CTCAE v5.0.
The trial is expected to commence recruitment on August 15, 2024, and conclude by August 15, 2031. Participants will be involved in the study for a maximum treatment period of 12 months. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be adults aged 18 years or older, with histologically confirmed primary NSCLC, and classified postoperatively in stages IB, IIA, IIB, IIIA, or IIIB (N2) according to the 8th edition of the International Association for the Study of Lung Cancer Staging Manual. Participants must have undergone complete surgical resection (R0) and received preoperative platinum-based chemotherapy combined with immunotherapy.
Participants will be randomly assigned to receive either the investigational treatment or a control, with neither the participants nor the investigators aware of the group assignments, ensuring a double-blind design. The study will be conducted under strict adherence to ethical guidelines, with informed consent obtained from all participants. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any condition that, in the opinion of the investigator, would make continued participation detrimental to the participant's health. The trial aims to provide valuable insights into the potential benefits of combining these therapies for improving outcomes in NSCLC patients.
Treatment
The clinical trial involves the administration of **Zimberelimab**, an experimental medication formulated as a **solution for infusion**. Zimberelimab is administered intravenously, with a maximum daily dose of 360 mg. The treatment period extends up to 12 months. The active substance, Zimberelimab, is a protein of other origin, and the product is not a pediatric formulation. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
In addition to Zimberelimab, the trial includes the administration of **Trodelvy**, a 200 mg powder for concentrate for solution for infusion. The active substance in Trodelvy is **Sacituzumab Govitecan**, also a protein of other origin. This medication is administered intravenously, with a maximum daily dose of 10 mg/kg. The treatment duration is similarly set for up to 12 months. Trodelvy is not a pediatric formulation, and its administration is closely monitored to ensure compliance with the prescribed dosing schedule.
Both Zimberelimab and Trodelvy are utilized as test products in this phase III clinical trial, which aims to evaluate the disease-free survival in patients with stage IB-IIIA-IIIB (N2) previously resected non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response after neoadjuvant treatment. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Compliance with the treatment protocol is ensured through regular monitoring and adherence checks.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **disease-free survival (DFS)**. DFS is defined as the length of time from randomization to the earliest event, which includes disease recurrence, the occurrence of any new lung cancer, or death from any cause. This primary endpoint will provide a measure of the treatment's effectiveness in prolonging the period during which patients remain free from disease.
Secondary endpoints include the assessment of overall survival (OS) at 12, 24, and 36 months following the initiation of adjuvant treatment. Additionally, the safety and tolerability of the combination of Sacituzumab Govitecan and Zimberelimab will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. These secondary measures will offer further insights into the long-term benefits and potential risks associated with the treatment regimen.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients diagnosed of primary non-small cell lung cancer, histologically confirmed
- Patients should be classified at diagnosis in stage IB, IIA, IIB, IIIA or IIIB (T3N2) according to 9th 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 (three) specific mediastinal ganglionic lobe stations (N2), one of which should include station 7, and at least one N1 station (including those resected with the tumor piece)
- 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
- PET-CT and brain CT before randomization to confirm the absence of distant disease.
- Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to randomization
- All patients are notified of the investigational nature of this study and signed a written informed 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 that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of trial treatment.
- For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate [< 1% per year] when used consistently and correctly, and to continue its use for 6 months after the last dose of trial treatment. Male patients should not donate sperm during this study and for at least 6 months after the last dose of trial treatment.
- Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs. The same rules are valid for male patients involved in this clinical study if they have a partner of childbirth potential. Male patients must always use a condom.
- Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
- Patient capable of proper therapeutic compliance and accessible for correct follow-up
- Patients with a life expectancy of at least more than 12 weeks
Exclusion Criteria
- 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 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.
- 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 Patients with relevant cardiac history, even when well controlled, should have a LVEF> 50% in the 12 weeks prior to randomization.
- 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 (> 10 mg daily prednisone equivalent) 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.
- History of allergy or hypersensitivity to any of the study drug components
- 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.
- Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
- 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.
- 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.
- 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.
- Treatment with systemic immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to inclusion.
- Patients with uncontrolled comorbidities that may affect the clinical trial compliance.
- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 15 Aug 2024 | 129 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 10 | 12 | PRD9351384 |
Zimberelimab | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 360 | 12 | PRD10273654 |