Phase II Trial of Chemotherapy and Atezolizumab in Stage IIIA/IIIB NSCLC with Atezolizumab Adjuvant and Maintenance Therapy
- Trial ID
- 2024-515984-68-00
- Protocol
- GECP 23/02
- Sponsor
- Fundacion GECP
Trial statistics
Objectives
The primary objective of this Phase II clinical trial is to evaluate the **Progression Free Survival (PFS)** rate at 18 months in the intent-to-treat population (ITT) for patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC). PFS is defined as the time from the initiation of treatment to the occurrence of disease progression or death. This measure is clinically relevant as it provides insight into the efficacy of the treatment regimen in delaying disease progression, which is crucial for improving patient outcomes in NSCLC.
Secondary objectives include:
- Resectability rate (%)
- Proportion of R0 resections (%)
- Pathological complete response (pCR) in the ITT population
- Major Pathological Response (MPR) rate
- PFS rate at 12 months
- PFS rate at 12 and 18 months in various patient subgroups based on surgical candidacy and pCR status
- Overall Survival (OS) rate at 12 and 18 months of treatment
- OS rate at 12 and 18 months in various patient subgroups based on surgical candidacy and pCR status
- Downstaging rate (%)
- Evaluation of the association between baseline levels of circulating tumor DNA (ctDNA) and OS and PFS
- Evaluation of the association between ctDNA clearance after neoadjuvant treatment and OS and PFS
- Identification of molecular alterations that may lead to treatment failure
- Measurement of minimal residual disease after surgery and its predictive capacity for PFS and OS
- Description of levels, relationships, and changes of molecular markers related to the immune response at diagnosis and during treatment, and their predictive value for various clinical outcomes
Participants
The clinical trial involves participants diagnosed with **non-small cell lung cancer (NSCLC)**, specifically those with stage IIIA to IIIB disease as per the 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology. The study population includes both male and female subjects aged over 18 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have adequate hematologic and organ function, as well as sufficient lung function, defined by specific laboratory criteria. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their ability to comply with therapeutic protocols and follow-up requirements, and they must have at least one measurable lesion by CT-SCAN. Lifestyle considerations include the use of effective contraception for both male and female participants of childbearing potential, with specific guidelines to prevent potential drug interactions. The trial excludes individuals with distant disease confirmed by PET-CT and brain CT or MRI at baseline. The sponsor has not disclosed the total number of participants involved in this study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **atezolizumab** in combination with chemotherapy for patients with stage IIIA and IIIB **non-small cell lung cancer (NSCLC)**. This is a Phase II, randomized, double-blind, controlled study. The primary objective is to assess the progression-free survival (PFS) rate at 18 months in the intent-to-treat population. The trial is expected to commence recruitment on May 2, 2025, and conclude by May 2, 2035. Participants will be involved in the study for a maximum treatment period of 19 months for those receiving atezolizumab, and up to 3 months for those receiving chemotherapy agents such as **carboplatin** and **paclitaxel**.
The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as histologically- or cytologically-documented NSCLC, adequate organ function, and performance status. Baseline assessments will include PET-CT and brain imaging to rule out distant disease. Following the screening, participants will be randomized to receive either the investigational treatment or a comparator. Regular follow-up visits will be scheduled to monitor treatment response, adverse events, and overall health status. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, non-compliance with study procedures or the emergence of any condition that contraindicates continued participation may also lead to early termination. The study will adhere to ethical guidelines, ensuring that all participants provide informed consent prior to any trial-related interventions. The trial aims to provide valuable insights into the potential benefits of atezolizumab as an adjuvant treatment following surgery or as maintenance therapy for non-resected patients after chemoradiotherapy.
Treatment
The clinical trial involves the administration of **Tecentriq** (atezolizumab), a concentrate for solution for infusion, as the experimental medication. Tecentriq is provided in a pharmaceutical form suitable for **intravenous use**. The dosage is set at 1200 mg, administered once every three weeks, with a maximum treatment period of 19 cycles. Atezolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF05. The administration of Tecentriq is monitored to ensure participant compliance, with dosing schedules strictly adhered to as per the trial protocol.
In addition to the experimental treatment, the trial includes the use of **Carboplatino Teva** (carboplatin) as a comparator treatment. This medication is also administered as an **injection** for intravenous use. The maximum daily dose of carboplatin is 750 mg, with a treatment period limited to 3 cycles. Carboplatin is a chemical-based substance, categorized under the ATC code L01XA02, and is utilized as part of the chemotherapy regimen in the study.
Another comparator treatment used in the trial is **Paclitaxel Teva** (paclitaxel), which is administered as an **injection** for intravenous use. The dosing for paclitaxel is calculated based on body surface area, with a maximum dose of 200 mg/m² per cycle, and a treatment period of 3 cycles. Paclitaxel is a chemical compound, classified under the ATC code L01CD01, and is also part of the chemotherapy regimen. Compliance with the administration schedule for both carboplatin and paclitaxel is closely monitored to ensure adherence to the trial protocol.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **Progression Free Survival (PFS)** rate at 18 months in the intent-to-treat population. PFS is defined as the time from the initiation of treatment to the occurrence of disease progression or death. This primary endpoint will provide a measure of the treatment's ability to delay disease progression in patients with stage IIIA and IIIB non-small cell lung cancer.
Secondary endpoints include a variety of measures to further assess efficacy. These include the resectability rate, the proportion of R0 resections, and the pathological complete response (pCR) in the intent-to-treat population. Additionally, the major pathological response (MPR) rate, PFS rates at 12 months, and overall survival (OS) rates at 12 and 18 months will be evaluated. The study will also explore the association between baseline levels of circulating tumor DNA (ctDNA) and both OS and PFS, as well as ctDNA clearance after neoadjuvant treatment. Molecular alterations that may lead to treatment failure will be identified, and minimal residual disease after surgery will be measured to predict PFS and OS. Changes in molecular markers related to the immune response will also be described to determine their predictive value for various outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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)
- 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.
- Patient capable of proper therapeutic compliance and accessible for correct follow-up
- Presence of at least one measurable lesion by CT-SCAN, as defined by RECIST v1.1.
- Patients with a life expectancy ≥12 weeks
- PET scan and brain CT or MRI at baseline to confirm the absence of distant disease. Positive mediastinal lymph nodes by PET scan must be confirmed histologically by mediastinoscopy/EBUS/EUS.
- ECOG (Performance status) 0-1
- Adequate hematologic and organ function defined by laboratory results obtained within 14 days prior to enrollment
- 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.
- Adequate lung function: Forced Expiratoy Volumen in 1 second (FEV1) >50% of normal volume and Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) >40% of normal value
- Patients aged > 18 years
- 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 men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined below: • With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 180 days after the final dose of chemotherapy. Men must refrain from donating sperm during this same period. • With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 180 days after the final dose of chemotherapy to avoid exposing the embryo. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria
- Patients with known sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene, ALK fusion oncogene.
- Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
- Weight loss >10% within the previous 3 months.
- Patients that receive previous treatment with antineoplasic drugs, chest radiotherapy, or previous surgery for lung cancer.
- 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
- 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.
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab or Tiragolumab formulation.
- "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 requires low-potency topical steroids. ▪ No acute exacerbations of underlying condition within the previous 12 months"
- 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.
- 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.
- Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
- 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).
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis.
- 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
- 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.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to be included in the study. Patients receiving prophylactic antibiotics are eligible.
- 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.
- 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.
- Patients with a superior vena cava syndrome.
- 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.
- Prior allogeneic bone marrow transplantation or solid organ transplant.
- 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.
- 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.
- 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.
- Treatment with any other investigational agent with therapeutic intent within 28 days prior to initiation of study treatment.
- "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."
- Patients with uncontrolled comorbidities that may affect the clinical trial compliance.
- Women who are pregnant or in the breastfeeding period.
- Sexually active 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 | 02 May 2025 | 97 |
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 |
|---|---|---|---|---|---|---|
Tecentriq 1 200 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 1200 | 19 | PRD5434939 |
Carboplatino Teva 10 mg/ml Concentrado para solución para perfusión | Comparator | CONCENTRADO PARA SOLUCIÓN PARA PERFUSIÓN | INTRAVENOUS USE | 750 | 3 | PRD11874602 |
Paclitaxel Teva 6 mg/ml concentrado para solución para perfusión EFG | Comparator | CONCENTRADO PARA SOLUCIÓN PARA PERFUSIÓN EFG | INTRAVENOUS USE | 200 | 3 | PRD721519 |