Evaluating 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)

Plain English Summary

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 is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Lung Non-Small Cell Carcinoma. This trial tests if an immunotherapy drug, atezolizumab, given after surgery can prevent early-stage lung cancer from returning. It is for patients who have had surgery to remove stage I non-small cell lung cancer. Participants will receive either atezolizumab, a combination of atezolizumab and another drug, or standard observation after surgery. The current standard approach after surgery is observation, which involves regular check-ups and tests. The trial aims to enroll 336 participants.

Official Summary

This phase III trial compares the effect of atezolizumab (or atezolizumab and recombinant human hyaluronidase) to standard observation for preventing cancer return after surgery (recurrence) in patients who have undergone a complete surgical removal (resection) of stage I non-small cell lung cancer (NSCLC). Patients who have undergone resection for lung cancer are typically followed by observation or active surveillance, which involves closely watching a patient's condition but not giving treatment unless there are changes in test results. During active surveillance, patients are given certain exams and tests done on a regular schedule. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Atezolizumab and recombinant human hyaluronidase is a formulation of atezolizumab combined with an enzyme called hyaluronidase, which helps increase tissue absorption of the drug. Giving atezolizumab or atezolizumab and recombinant human hyaluronidase after resection may be effective for preventing NSCLC recurrence, and may be a better approach to treating patients with stage I NSCLC than the usual observation approach.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must have had surgery for stage IA3 or IB non-small cell lung cancer. The cancer must have been completely removed with clear margins, and specific lymph node sampling must have been done. Patients must have a specific marker (PD-L1 TPS ≥ 50%) on their tumor and not have certain genetic mutations (EGFR, ALK). Patients must be at least 18 years old, in good general health, and not have active autoimmune diseases or certain other medical conditions. This trial is studying Lung Non-Small Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

Disease-free survival means the trial will measure how long patients live without their cancer returning or developing a new lung cancer, or dying, for up to 10 years. The specific primary outcome measures are: Disease-free survival (From randomization to disease recurrence, second lung primary, or death, assessed up to 10 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to find a better way to prevent early-stage lung cancer from coming back after surgery, addressing a need for more effective adjuvant therapies. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Lung Non-Small Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial targets a significant market of early-stage lung cancer patients, with atezolizumab being a known immunotherapy, suggesting a competitive landscape but potential for improved treatment outc Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer stage and health. Participation involves receiving either an IV or under-the-skin injection of the study drug, or being monitored, and attending regular appointments for tests and check-ups. You will need to provide blood samples and undergo CT scans as part of the trial. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 336 participants

Interventions

• BIOLOGICAL: Atezolizumab — Given IV
• BIOLOGICAL: Atezolizumab and Recombinant Human Hyaluronidase — Given SC
• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• PROCEDURE: Computed Tomography — Undergo CT
• OTHER: Patient Observation — Undergo observation

Primary Outcomes

• Disease-free survival (From randomization to disease recurrence, second lung primary, or death, assessed up to 10 years)

Secondary Outcomes

• Overall survival (From randomization to death, assessed up to 10 years)
• Lung cancer-specific survival (Up to 10 years)
• Recurrence-free survival (From randomization to recurrence or death, assessed up to 10 years)
• Rate of loco-regional recurrence (Up to 10 years)
• Rate of distant recurrence (Up to 10 years)

Full Eligibility Criteria

Inclusion Criteria:

* 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

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Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage I Lung Cancer
• Adjuvant Therapy
• Immunotherapy
• Cancer Recurrence
• Oncology
• Thoracic Surgery
• Lung Cancer Surgery
• Cancer Treatment

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