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Testing the Impact of an Anti-Cancer Drug, Atezolizumab, After Surgery to Prevent Early Stage Non-small Cell Lung Cancer From Returning, AASI-NSCLC Trial Phase 3 336 Immuntherapie
I. To compare disease-free survival (DFS) in the intent-to-treat patient population, among patients randomized to receive atezolizumab for one year (Arm B) versus (vs.) observation (Arm A).
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between patients randomized to atezolizumab versus observation.
II. To compare recurrence-free survival (RFS) between patients randomized to atezoliz...
Mehr anzeigenEvaluating Adjuvant Atezolizumab or Atezolizumab and Hyaluronidase-TQJS to Prevent Recurrence in Stage I Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase III Trial (AASI-NSCLC)
- NCI-2026-00505
- NCI-2026-00505 (Registerkennung) (CTRP (Clinical Trial Reporting Program))
- A082302 (Andere Kennung) (Alliance for Clinical Trials in Oncology)
- A082302 (Andere Kennung) (CTEP)
- U10CA180821 (Zuwendung/Vertrag der US-NIH)
| Teilnehmergruppe/Studienarm | Intervention/Behandlung |
|---|---|
Aktives VergleichspräparatArm A (observation) Patients undergo observation for 1 year. Patients also undergo CT and optional collection of blood samples throughout the trial. | Biospezimen-Sammlung Undergo collection of blood samples Computertomographie Undergo CT Patientenbeobachtung Undergo observation |
ExperimentellArm B (atezolizumab) Patients receive atezolizumab IV over 60 minutes or atezolizumab and recombinant human hyaluronidase SC over 7 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year (17 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and optional collection of blood samples throughout the trial. | Atezolizumab Given IV Atezolizumab and Recombinant Human Hyaluronidase Given SC Biospezimen-Sammlung Undergo collection of blood samples Computertomographie Undergo CT |
| Ergebnismessung | Beschreibung der Messung | Zeitrahmen |
|---|---|---|
Disease-free survival | Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. The rates at various timepoints and medians for each arm will be estimated using the Kaplan-Meier estimator. The 95% confidence interval will be calculated using Greenwood's formula and based on a log-log transformation applied to the survival function. Hazard ratios will be estimated using a stratified Cox regression model. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic regimen, histology, and performance status. | From randomization to disease recurrence, second lung primary, or death, assessed up to 10 years |
| Ergebnismessung | Beschreibung der Messung | Zeitrahmen |
|---|---|---|
Overall survival | Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. | From randomization to death, assessed up to 10 years |
Lung cancer-specific survival | Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. | Up to 10 years |
Recurrence-free survival | Recurrence will be characterized as loco-regional or distant. Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. | From randomization to recurrence or death, assessed up to 10 years |
Rate of loco-regional recurrence | Rates between arms will be compared with Fisher's exact test. The difference in recurrence rates between arms will be estimated by the Miettinen-Nurminen method, and its 95% confidence interval will be provided. Multivariable logistic regression will be used to evaluate the treatment effect on the recurrence rates while adjusting for significant baseline covariates. | Up to 10 years |
Rate of distant recurrence | Rates between arms will be compared with Fisher's exact test. The difference in recurrence rates between arms will be estimated by the Miettinen-Nurminen method, and its 95% confidence interval will be provided. Multivariable logistic regression will be used to evaluate the treatment effect on the recurrence rates while adjusting for significant baseline covariates. | Up to 10 years |
Incidence of grade ≥ 3 adverse events | The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5. The frequency and percentage of grade ≥ 3 adverse events will be compared between the study arms using Fisher's exact test. | Up to 10 years |
Pathologically stage IA3 or IB NSCLC per American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 9th edition
- Note: Tumors with any histology are allowed including both squamous and non-squamous subtypes, except those containing small-cell morphology. Non-squamous histology includes adenocarcinoma, large cell neuroendocrine, poorly differentiated tumors and adenosquamous, etc
Patient must have undergone complete surgical resection with negative margins (complete R0 resection). Surgical resection must be lobectomy or higher, unless the tumor measured no more than 2 cm based on clinical staging, where sub-lobar resection, e.g., wedge or segmentectomy, will be acceptable
- Note: For patients who underwent sub-lobar resection for clinical tumors size of ≤ 2.0 cm, must have CT chest confirming tumor size within 60 days of surgical resection. Patients who received a lobectomy or higher do not require to fulfill this imaging criteria
Patient must have undergone adequate nodal sampling as defined by Commission on Cancer, 2020 Standard. Adequate nodal sampling includes pathological evaluation of at least one (named and/or numbered) hilar station (level 10 or higher) and at least three distinct (named and or numbered) mediastinal stations (level 2-9)
PD-L1 immunohistochemistry showing tumor proportion score (TPS) ≥ 50%, by an Food and Drug Administration (FDA)-approved assay including but not limited to SP263, SP142, 22C3, 28-8, performed either on surgical specimen or biopsy specimen
No EGFR exon 19 deletion (del) or L858R mutation or ALK fusion; molecular testing may have been performed either on surgical specimen or biopsy specimen. Tumors with purely squamous histology are not required to undergo EGFR or ALK gene testing
Patient to be registered to A082302 no earlier than 21 days and no later than 77 days from surgical resection
Recovered from surgical resection as determined by the treating provider or the investigator
No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
Patient must NOT have uncontrolled intercurrent illness, including but not limited to serious ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class ≥ III), unstable angina, or unstable arrhythmia
No current pneumonitis or history of (non-infectious) pneumonitis that required steroids or history of interstitial lung disease (ILD)
No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease modifying agents, corticosteroids, or immunomodulatory agents). Replacement therapy (e.g., thyroid for history of autoimmune thyroiditis, insulin for type I or II diabetes, corticosteroids for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
No known hypersensitivity (≥ grade 3) to atezolizumab and/or any of its excipients
No live vaccine within 30 days prior to registration. Examples include but are not limited to: measles, mumps, rubella, varicella, yellow fever, Bacillus Calmette-Guerin (BCG), typhoid, nasally administered influenza
No history of prior allogeneic bone marrow, stem cell, or solid organ transplant
Patient has not received continuous systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days prior to registration, with the following exceptions:
- Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen or chronic obstructive pulmonary disease \[COPD\] exacerbation) is permitted
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
Absolute neutrophil count (ANC) ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 x upper limit of normal (ULN), except patients with Gilbert syndrome who can have total bilirubin < 3.0 mg/dl
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)
Creatinine clearance ≥ 30 mL/min (using standard Cockcroft-Gault formula, unless measured creatinine clearance \[CrCl\] is available and meet the specified threshold)
Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
- Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- HIV: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. Patients with no known history of HIV do not require any testing
Hepatitis B and hepatitis C: No active hepatitis B (defined as negative for hepatitis B \[HepB\] deoxyribonucleic acid \[DNA\], and positive for HepB surface antibody) or hepatitis C (defined as hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] detected) infection. If there is a history of either infection, patient should be negative for active disease, for hepatitis B negative for hepatitis B virus surface antigen (HBsAg), and for hepatitis C - negative for HCV RNA (qualitative). Patients with no known history of chronic hepatitis do not require any testing
No active infection requiring systemic therapy
Cardiac function: Patients with known history or current symptoms of heart failure, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better