Phase II clinical trial of chemotherapy + atezolizumab for stage IIIa and IIIb non-small cell lung cancer followed by atezolizumab as adjuvant treatment after surgery and atezolizumab as maintenance treatment for non-resected patients after chemoradiotherapy

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

20 May 2025 → ongoing

Decision date (initial)

2025-01-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective is to evaluate the Progression free survival (PFS) rate at 18 months in the intent-to-treat population (ITT). Progression free survival (PFS) defined as the time from initiation of treatment to the occurrence of disease progression or death.

Secondary objectives 20

1. 1. Resectability rate (%)
2. 2. Proportion of R0 resections (%)
3. 3. Pathological complete response (pCR) in the intent-to-treat population (ITT)
4. 4. Major Pathological response (MPR) rate
5. 5. PFS rate at 12 months
6. 6. PFS rate at 12 and 18 months in patients candidates for surgery and in patients not candidates for surgery with pCR and clinical follow up
7. 7. PFS rate at 12 and 18 months in patients candidate for surgery and in patients not candidates for surgery with pCR and adjuvant treatment
8. 8. PFS rate at 12 and 18 months in patients who are candidates for surgery with pCR
9. 9. PFS rate at 12 and 18 months in patients who are candidates for surgery with No pCR
10. 10. Overall survival (OS) rate at 12 and 18 months of treatment
11. 11. OS rate at 12 and 18 months in patients candidates of for surgery and in patients not candidates for surgery with pCR and clinical follow up
12. 12. OS rate at 12 and 18 months in patients candidate for surgery and in patients not candidates for surgery with pCR and adjuvant treatment
13. 13. OS rate at 12 and 18 months in patients who are candidates for surgery with pCR
14. 14. OS rate at 12 and 18 months in patients who are candidates for surgery with no pCR
15. 15. Downstaging rate (%)
16. 16. To evaluate whether there is a significant association between baseline levels of ctDNA and OS and PFS.
17. 17. To evaluate whether there is a significant association between ctDNA clearance (no detection of ctDNA) after neoadjuvant treatment and OS and PFS.
18. 18. To identify molecular alterations that may lead to treatment failure.
19. 19. To measure minimal residual disease after surgery and evaluate its capacity to predict PFS and OS
20. 20. To describe the levels, relationships and changes of molecular markers related to the immune response at diagnosis and during treatment, as well as, whether they are predictive for pathological Response, ORR, ctDNA negativization, adverse events, sites of first failure, PFS and OS

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA – IIIB disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology)
2. 2. PET-CT and brain CT or MRI at baseline to confirm the absence of distant disease
3. 3. ECOG (Performance status) 0-1
4. 4. Adequate hematologic and organ function defined by laboratory results obtained within 14 days prior to enrollment
5. 5. 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.
6. 6. Adequate lung function: Forced Espiratoy Volumen in 1 second (FEV1) >50% of normal volume and Difusion Capacity of the Lungs for Carbon Monoxide (DLCO) >40% of normal value
7. 7. Patients aged > 18 years
8. 8. 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.
9. 9. 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.
10. 10. 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.
11. 11. Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 8 days prior to initiation of study drug.
12. 12. Patient capable of proper therapeutic compliance and accessible for correct follow-up
13. 13. Presence of at least one measurable lesion by CT-SCAN, as defined by RECIST v1.1.
14. 14. Patients with a life expectancy ≥12 weeks

Exclusion criteria 30

1. 1. Patients with known sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene, ALK fusion oncogene.
2. 2. Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
3. 3. Weight loss >10% within the previous 3 months.
4. 4. Patients that receive previous treatment with antineoplasic drugs, chest radiotherapy, or previous surgery for lung cancer.
5. 5. Malignancies other than NSCLC within 3 years prior to enrolment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 3-year OS > 90%) treated with expected curative outcome
6. 6. 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.
7. 7. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab or Tiragolumab formulation.
8. "8. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen are eligible for this study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: ▪ Rash must cover less than 10% of body surface area (BSA). ▪ Disease is well controlled at baseline and only requiring low-potency topical steroids. ▪ No acute exacerbations of underlying condition within the previous 12 months"
9. 9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
10. 10. Positive test for HIV. All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical study.
11. 11. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
12. 12. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA (vaccinated patients are excluded).
13. 13. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
14. 14. Active tuberculosis.
15. 15. Symptomatic neuropathy (sensory) grade > 1 according to the NCI Common Toxicity Criteria for Adverse Events v5.0 and that were not related to the tumor
16. 16. Severe infections within 4 weeks prior to be included in the study, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
17. 17. Received therapeutic oral or IV antibiotics within 2 weeks prior to be included in the study. Patients receiving prophylactic antibiotics are eligible.
18. 18. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina.
19. 19. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
20. 20. Patients with a superior vena cava syndrome.
21. 21. Major surgical procedure other than for diagnosis within 28 days prior to inclusion or anticipation of need for a major surgical procedure during the course of the study.
22. 22. Prior allogeneic bone marrow transplantation or solid organ transplant.
23. 23. Administration of a live, attenuated vaccine within 4 weeks before inclusion or anticipation that such a live attenuated vaccine will be required during the study.
24. 24. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
25. 25. 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.
26. 26. Treatment with any other investigational agent with therapeutic intent within 28 days prior to initiation of study treatment.
27. "27. 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 who have received acute, low-dose (≤ 10 mg oral prednisone or equivalent), systemic immunosuppressant medications may be enrolled in the study. The use of corticosteroids (≤ 10 mg oral prednisone or equivalent) for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency is allowed."
28. 28. Patients with uncontrolled comorbidities that may affect the clinical trial compliance.
29. 29. Women who are pregnant or in the breastfeeding period.
30. 30. 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. Evaluate the Progression free survival (PFS) rate at 18 months in the intent-to-treat population. Progression free survival (PFS) defined as the time from initiation of treatment to the occurrence of disease progression or death.

Secondary endpoints 20

1. 1. Resectability rate (%)
2. 2. Proportion of R0 resections (%)
3. 3. Pathological complete response (pCR) in the intent-to-treat population (ITT)
4. 4. Major Pathological response (MPR) rate
5. 5. PFS rate at 12 months
6. 6. PFS rate at 12 and 18 months in patients candidates for surgery and in patients not candidates for surgery with pCR and clinical follow up
7. 7. PFS rate at 12 and 18 months in patients candidate for surgery and in patients not candidates for surgery with pCR and adjuvant treatment
8. 8. PFS rate at 12 and 18 months in patients who are candidates for surgery with pCR
9. 9. PFS rate at 12 and 18 months in patients who are candidates for surgery with No pCR
10. 10. Overall survival (OS) rate at 12 and 18 months of treatment
11. 11. OS rate at 12 and 18 months in patients candidates of for surgery and in patients not candidates for surgery with pCR and clinical follow up
12. 12. OS rate at 12 and 18 months in patients candidate for surgery and in patients not candidates for surgery with pCR and adjuvant treatment
13. 13. OS rate at 12 and 18 months in patients who are candidates for surgery with pCR
14. 14. OS rate at 12 and 18 months in patients who are candidates for surgery with no pCR
15. 15. Downstaging rate (%)
16. 16. To evaluate whether there is a significant association between baseline levels of ctDNA and OS and PFS.
17. 17. To evaluate whether there is a significant association between ctDNA clearance (no detection of ctDNA) after neoadjuvant treatment and OS and PFS.
18. 18. To identify molecular alterations that may lead to treatment failure.
19. 19. To measure minimal residual disease after surgery and evaluate its capacity to predict PFS and OS
20. 20. To describe the levels, relationships and changes of molecular markers related to the immune response at diagnosis and during treatment, as well as, whether they are predictive for pathological Response, ORR, ctDNA negativization, adverse events, sites of first failure, PFS and OS

Investigational products

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

Test 1

Comparator 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 · 21 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 12 files

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

Application history

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