NRG Oncology/Alliance LU005: A Phase II/III Randomized Study of Chemoradiation vs. Chemoradiation Plus Atezolizumab in Limited Stage Small Cell Lung Cancer

Purpose/Objective(s)Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation.Materials/MethodsPatients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab delivered concurrently with thoracic radiation, every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), gender, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). The overall sample size for phase II/III will be 506. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. Correlative studies will include blood and tissue based tumor mutational burden analysis, with the hypothesis that higher mutational burden will predict for improved PFS in the experimental arm.ResultsAs of 3/01/2021, 374 sites are approved to enroll patients. Two-hundred patients have been accrued. Current enrollment is ahead of projected accrual.ConclusionLU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. Accrual remains robust in spite of the ongoing COVID 19 pandemic. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation. Patients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab delivered concurrently with thoracic radiation, every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), gender, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). The overall sample size for phase II/III will be 506. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. Correlative studies will include blood and tissue based tumor mutational burden analysis, with the hypothesis that higher mutational burden will predict for improved PFS in the experimental arm. As of 3/01/2021, 374 sites are approved to enroll patients. Two-hundred patients have been accrued. Current enrollment is ahead of projected accrual. LU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. Accrual remains robust in spite of the ongoing COVID 19 pandemic. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech.