Study of treatment with sacituzumab and zimkberelimab for patients with lung cancer confined to the chest and previously operated on who were not disease-free.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion GECP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Feb 2025 → ongoing

Decision date (initial)

2024-08-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundacion GECP

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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.

Secondary objectives 2

1. 1. Overall survival (OS): at 12, 24 and 36 months after the start of adjuvant treatment
2. 2. Safety and tolerability of the combination of Sacituzumab Govitecan + Zimberelimab according to CTCAE v5.0

Conditions and MedDRA coding

Resectable Non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. 1. Patients diagnosed of primary non-small cell lung cancer, histologically confirmed
2. 2. 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
3. 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 (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)
4. 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. 5. Only patients that do not achieve pathological complete response (pCR) seen in the surgical piece after neoadjuvant therapy are eligible.
6. 6. Preoperative (neoadjuvant) use of platinum-based chemotherapy + immunotherapy (anti PD-1) is mandatory.
7. 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. 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. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
10. 10. Patients aged ≥ 18 years.
11. 11. PDL1 value analysed locally
12. 12. PET-CT and brain CT before randomization to confirm the absence of distant disease.
13. 13. Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to randomization
14. 14. 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.
15. 15. 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.
16. 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 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.
17. 17. 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.
18. 18. 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.
19. 19. Patient capable of proper therapeutic compliance and accessible for correct follow-up
20. 20. Patients with a life expectancy of at least more than 12 weeks

Exclusion criteria 24

1. 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. 2. T4 patients with invasion of heart, great vessels, carina, trachea, oesophagus or spine
3. 3. Patients with ALK translocation, STK11 o KEAP1 known mutations before inclusion in this trial.
4. 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. 5. Patients with a combination of microcytic and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
6. 6. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of randomization.
7. 7. Patients that received live attenuated vaccines within 30 days prior to randomization
8. 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. 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. 10. 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.
11. 11. Pregnant or breastfeeding women
12. 12. Patients in whom R0 resection cannot be confirmed.
13. 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. 14. 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.
15. 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. 16. History of allergy or hypersensitivity to any of the study drug components
17. 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. 18. 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.
19. 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. 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. 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. 22. 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.
23. 23. Patients with uncontrolled comorbidities that may affect the clinical trial compliance.
24. 24. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 2

1. 1. Overall survival (OS): at 12, 24 and 36 months after the start of adjuvant treatment
2. 2. Safety and tolerability of the combination of Sacituzumab Govitecan + Zimberelimab according to CTCAE v5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Scientific contact point

Organisation

Fundacion GECP

Contact name

Mariano Provencio

Public contact point

Organisation

Fundacion GECP

Contact name

Maria Fernández

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications