Atezolizumab Immunotherapy With or Without Tiragolumab for Patients With Unresectable Stage III NSCLC
- Conditions
- NSCLC
- Registration Number
- NCT05798663
- Lead Sponsor
- Alliance Foundation Trials, LLC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 178
Inclusion Criteria:<br><br> 1. Newly pathologically proven diagnosis of stage IIIA/B/C (per AJCC 8) NSCLC<br><br> 2. Age at least 18 years.<br><br> 3. Availability of a representative tumor specimen that is suitable for BOTH<br> determination of PD-L1 status via local testing and, independently, other required<br> correlative study biomarkers. Tissue submission should include:<br><br> a. A representative FFPE tumor specimen in a paraffin block, along with an<br> associated pathology report, which will be sent to the biorepository. Patients may<br> be eligible despite not meeting this additional tissue requirement at the discretion<br> of the AFT Study Team. If institutional policy prevents the submission of a block,<br> refer to the Correlative Science Manual (CSM) for alternative submission<br> instructions.<br><br> 4. If archival tumor tissue is unavailable or is determined to be unsuitable for<br> required testing, tumor tissue must be obtained from a biopsy performed at<br> screening. Questions about biopsy adequacy should be directed to the study team. No<br> active autoimmune disease or uncontrolled infection<br><br> 5. FEV1 = 1.2L or > 40% predictive<br><br> 6. No underlying heart or lung disease precluding treatment per protocol.<br><br> 7. Measurable (RECIST v1.1) stage IIIA, IIIB or IIIC disease per AJCC 8.<br><br> 8. Patients must be considered unresectable or inoperable. Patients who decline surgery<br> for stage III NSCLC are also eligible. Patients with nodal recurrence after surgery<br> for early-stage NSCLC are eligible if the following criteria are met:<br><br> - No prior systemic therapy or radiation for this lung cancer<br><br> - Prior curative-intent surgery at least 3 months prior to the nodal recurrence<br> Note: Patients may be medically unfit for surgery, (e.g., due to general<br> anesthesia risk), but remain fit for chemoradiotherapy. Thus, the criterion<br> does not necessarily have to exclude all patients who are medically unfit for<br> surgery.<br><br> 9. Stage III A/B/C disease (per AJCC 8) with minimum diagnostic evaluation to include:<br><br> - History/physical examination within 4 weeks<br><br> - Contrast enhanced CT of the chest including upper abdomen (or CT without<br> contrast if contrast is medically contraindicated) within 4 weeks<br><br> - MRI of the brain with contrast (or CT with contrast if MRI is medically<br> contraindicated) within 6 weeks<br><br> - PET/CT skull to thigh within 6 weeks If pleural fluid is visible on CT scan,<br> thoracentesis to exclude malignancy should be obtained unless the effusion is<br> too small to tap in which case the patient is eligible.<br><br> 10. Patients must be at least 4 weeks from major surgery and must be fully recovered.<br><br> 11. Adequate hematologic and end organ function, defined by the following laboratory<br> results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1);<br> if repeat labs are obtained on or prior to C1D1 they must re-meet eligibility<br> criteria to treat):<br><br> - ANC = 1500 cells/µL<br><br> - WBC counts > 2500/ µ L<br><br> - Lymphocyte count = 500/ µ L<br><br> - Platelet count = 100,000/ µ L<br><br> - Hemoglobin = 9.0 g/dL (patients may be transfused to meet this criterion).<br><br> - Total bilirubin = 1.5 · upper limit of normal (ULN) with the following<br> exception:<br><br> - Patients with known Gilbert disease who have serum bilirubin level = 3 · ULN<br> may be enrolled.<br><br> - AST, ALT and Alkaline phosphatase = 2.5 · ULN<br><br> - Serum albumin = 25 g/L (2.5 g/dL)<br><br> - For patients not receiving therapeutic anticoagulation: INR and aPTT = 1.5 ·<br> ULN<br><br> - For patients receiving therapeutic anticoagulation: stable anticoagulant<br> regimen<br><br> - Serum creatinine = 1.5 · ULN or creatinine clearance = 45 mL/min on the basis<br> of the Cockcroft-Gault glomerular filtration rate estimation:<br><br> - (140 - age) · (weight in kg) · (0.85 if female) 72 · (serum creatinine in<br> mg/dL)<br><br> 12. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.<br><br> 13. Negative HIV test at screening with the following exception: patients with a<br> positive HIV test at screening are eligible provided they are stable on<br> anti-retroviral therapy, have a CD4+ T-cell count > 200/vL, and have an undetectable<br> viral load.<br><br> 14. Negative hepatitis B surface antigen (HBsAg) test at screening<br><br> 15. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb<br> at screening accompanied by either of the following:<br><br> - Negative total hepatitis B core antibody (HBcAb)<br><br> - Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA<br> < 500 IU/mL<br><br> - The HBV DNA test will be performed only for patients who have a negative HBsAg<br> test, a negative HBsAb test, and a positive total HBcAb test.<br><br> 16. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV<br> antibody test followed by a negative HCV RNA test at screening. The HCV RNA test<br> will be performed only for patients who have a positive HCV antibody test.<br><br> 17. Non-pregnant and non-nursing. The effect of atezolizumab and tiragolumab on the<br> fetus is unknown.<br><br> 18. For women of childbearing potential: agreement to remain abstinent (refrain from<br> heterosexual intercourse) or use contraception, and agreement to refrain from<br> donating eggs, as defined below:<br><br> - Women must remain abstinent (refrain from heterosexual intercourse) or use<br> contraceptive methods with a failure rate of < 1% per year during the treatment<br> period and for 90 days after the final dose of tiragolumab, 5 months after the<br> final dose of atezolizumab, and 6 months after the final dose of paclitaxel,<br> pemetrexed, gemcitabine, carboplatin or cisplatin. Women must refrain from<br> donating eggs during this same period.<br><br> - A woman is considered to be of childbearing potential if she is postmenarchal,<br> has not reached a postmenopausal state (= 12 continuous months of amenorrhea<br> with no identified cause other than menopause), and is not permanently<br> infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or<br> uterus) or another cause as determined by the investigator (e.g., Müllerian<br> agenesis). The definition of childbearing potential may be adapted for<br> alignment with local guidelines or regulations.<br><br> - Examples of contraceptive methods with a failure rate of < 1% per year include<br> bilateral tubal ligation, male sterilization, hormonal contraceptives that<br> inhibit ovulation, hormone-releasing intrauterine devices, and copper<br> intrauterine devices.<br><br> - The reliability of sexual abstinence should be evaluated in relation to the<br> duration of the clinical trial and the preferred and usual lifestyle of the<br> patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or<br> postovulation methods) and withdrawal are not adequate methods of<br> contraception. If required per local guidelines or regulations, locally<br> recognized adequate methods of contraception and information about the<br> reliability of abstinenc
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the progression-free survival (PFS) of patients treated with neoadjuvant, concurrent and adjuvant atezolizumab with or without tiragolumab.
- Secondary Outcome Measures
Name Time Method Overall survival (OS);overall response (ORR);Safety of the two regimens