Randomized Phase II Trial of Neoadjuvant and Adjuvant Atezolizumab With or Without Tiragolumab in Conjunction With Chemoradiotherapy for Unresectable Stage III NSCLC

Plain English Summary

Atezolizumab Immunotherapy With or Without Tiragolumab for Patients With Unresectable Stage III NSCLC is a Phase 2 clinical trial sponsored by Alliance Foundation Trials, LLC. studying NSCLC. This trial tests if adding atezolizumab and tiragolumab to standard chemoradiotherapy improves outcomes for patients with unresectable Stage III lung cancer. It is for adults diagnosed with Stage IIIA, IIIB, or IIIC non-small cell lung cancer (NSCLC) that cannot be surgically removed. Participants will receive standard chemoradiotherapy along with one of two immunotherapy drug combinations. Standard treatment options for this stage of lung cancer include chemoradiotherapy alone or, in some cases, surgery followed by other treatments. The trial aims to enroll 178 participants.

Official Summary

This is a phase II trial of neoadjuvant and adjuvant atezolizumab with or without tiragolumab in conjunction with chemoradiotherapy for unresectable stage III NSCLC.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a new diagnosis of Stage IIIA, IIIB, or IIIC NSCLC. Patients must have lung cancer that cannot be removed by surgery, or who choose not to have surgery. Individuals must have adequate lung function (FEV1 of at least 1.2L or >40% predicted) and no active autoimmune diseases or uncontrolled infections. Patients with certain prior treatments for lung cancer or specific heart/lung conditions may not be eligible. This trial is studying NSCLC, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients live without their cancer getting worse, indicating how effective the new drug combinations are at controlling the disease. The specific primary outcome measures are: To determine the progression-free survival (PFS) of patients treated with neoadjuvant, concurrent and adjuvant atezolizumab with or without tiragolumab. (2 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 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for better treatments for unresectable Stage III NSCLC, aiming to improve survival and reduce the risk of cancer progression where current options are limited. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets NSCLC, where improved treatment options are needed.

Investor Insight

This trial explores novel immunotherapy combinations in a significant market for lung cancer treatments, with potential to improve upon existing standards of care and gain market share if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific type and stage of lung cancer. Be prepared for regular clinic visits for treatments, monitoring, and tests over a period of about 2 years. Understand that you will receive standard chemotherapy and radiation alongside new immunotherapy drugs. The trial is being conducted at 15 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: 178 participants

Interventions

• DRUG: Atezolizumab — Atezolizumab will be given to participants either intravenously at a dosage of 1200mg or subcutaneously at a dosage of 1875 mg on Day 1 of each 21-day cycle for Arms A, B, and C, and on days 1 and 22 of concurrent chemoradiotherapy for Arm C only.
• DRUG: Tiragolumab — Tiragolumab will be given to participants intravenously at a dosage of 600 mg on day 1 of each 21-day cycle (Arms B and C), and on days 1 and 22 of concurrent chemoradiotherapy (Arm C only).

Primary Outcomes

• To determine the progression-free survival (PFS) of patients treated with neoadjuvant, concurrent and adjuvant atezolizumab with or without tiragolumab. (2 years)

Secondary Outcomes

• Overall survival (OS) (2 years)
• overall response (ORR) (2 years)
• Safety of the two regimens (1 year)

Full Eligibility Criteria

Inclusion Criteria:

1. Newly pathologically proven diagnosis of stage IIIA/B/C (per AJCC 8) NSCLC
2. Age at least 18 years.
3. Availability of a representative tumor specimen that is suitable for BOTH determination of PD-L1 status via local testing and, independently, other required correlative study biomarkers. Tissue submission should include:

   1. A representative FFPE tumor specimen in a paraffin block, along with an associated pathology report, which will be sent to the biorepository. If institutional policy prevents the submission of a block, refer to the Correlative Science Manual (CSM) for alternative submission instructions.
   2. If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Questions about biopsy adequacy should be directed to the study team.
   3. Patients may still be eligible after these two points (3a and 3b) have been attempted/considered, at the discretion of the AFT Study Team.
4. No active autoimmune disease or uncontrolled infection
5. FEV1 ≥ 1.2L or \> 40% predictive
6. No underlying heart or lung disease precluding treatment per protocol.
7. Measurable (RECIST v1.1) stage IIIA, IIIB or IIIC disease per AJCC 8.
8. Patients must be considered unresectable or inoperable. Patients who decline surgery for stage III NSCLC are also eligible. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:

   * No prior systemic therapy or radiation for this lung cancer
   * Prior curative-intent surgery at least 3 months prior to the nodal recurrence Note: Patients may be medically unfit for surgery, (e.g., due to general anesthesia risk), but remain fit for chemoradiotherapy. Thus, the criterion does not necessarily have to exclude all patients who are medically unfit for surgery.
9. Stage III A/B/C disease (per AJCC 8) with minimum diagnostic evaluation to include:

   * History/physical examination within 4 weeks
   * Contrast enhanced CT of the chest including upper abdomen (or CT without contrast if contrast is medically contraindicated) within 4 weeks
   * MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 6 weeks
   * PET/CT skull to thigh within 6 weeks If pleural fluid is visible on CT scan, thoracentesis to exclude malignancy should be obtained unless the effusion is too small to tap in which case the patient is eligible.
10. Patients must be at least 4 weeks from major surgery and must be fully recovered.
11. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1); if repeat labs are obtained on or prior to C1D1 they must re-meet eligibility criteria to treat):

    * ANC ≥ 1500 cells/µL
    * WBC counts \> 2500/ µ L
    * Lymphocyte count ≥ 500/ µ L
    * Platelet count ≥ 100,000/ µ L
    * Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this criterion).
    * Total bilirubin ≤ 1.5 ⋅ upper limit of normal (ULN) with the following exception:
    * Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ⋅ ULN may be enrolled.
    * AST, ALT and Alkaline phosphatase ≤ 2.5 ⋅ ULN
    * Serum albumin ≥ 25 g/L (2.5 g/dL)
    * For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 ⋅ ULN
    * For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
    * Serum creatinine ≤ 1.5 ⋅ ULN or creatinine clearance ≥ 45 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
    * (140 - age) ⋅ (weight in kg) ⋅ (0.85 if female) 72 ⋅ (serum creatinine in mg/dL)
12. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
13. Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4+ T-cell count \> 200/vL, and have an undetectable viral load.
14. Negative hepatitis B surface antigen (HBsAg) test at screening
15. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:

    * Negative total hepatitis B core antibody (HBcAb)
    * Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA \< 500 IU/mL
    * The HBV DNA test will be performed only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
16. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
17. Non-pregnant and non-nursing. The effect of atezolizumab and tiragolumab on the fetus is unknown.
18. For women of childbearing potential: agreement to remain abstinent (r

Trial Locations

• University of California San Diego Moores Cancer Center, La Jolla, California, United States
• Kaiser Permanente Oakland Medical Center, Oakland, California, United States
• Kaiser Permanente Roseville Medical Center, Roseville, California, United States
• Kaiser Permanente San Francisco Medical Center, San Francisco, California, United States
• Kaiser Permanente Santa Clara Medical Center, Santa Clara, California, United States
• Kaiser Permanente Vallejo Medical Center, Vallejo, California, United States
• Rush University Medical Center, Chicago, Illinois, United States
• Washington University Siteman Cancer Center, St Louis, Missouri, United States
• Missouri Baptist Medical Center, St Louis, Missouri, United States
• University of Nebraska Medical Center, Omaha, Nebraska, United States
• ...and 5 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer (NSCLC)
• Stage III Lung Cancer
• Unresectable Lung Cancer
• Lung Cancer Immunotherapy
• Chemoradiotherapy
• Thoracic Oncology
• Oncology
• Cancer Research
• Advanced Lung Cancer
• Metastatic Lung Cancer

More NSCLC Trials

View all NSCLC clinical trials