P3.02c-050 IMpower010: Phase III Study of Atezolizumab vs BSC after Adjuvant Chemotherapy in Patients with Completely Resected NSCLC: Topic: IT

Abstract

Early-stage non-small cell lung cancer (NSCLC) is treated surgically, but 30%–70% of patients experience post-resection recurrence and succumb to disease. Adjuvant chemotherapy is the standard of care for fully resected NSCLC (stages IB [tumors ≥4 cm]-IIIA), and although cisplatin-based chemotherapy provides some benefit, the 5-year absolute survival benefit is ≈5%, underscoring the unmet need. Atezolizumab is an anti-PD-L1 monoclonal antibody that inhibits PD-L1 from binding to its receptors PD-1 and B7.1, thereby restoring anti-tumor immune response. Atezolizumab monotherapy has demonstrated promising efficacy and tolerable safety in patients with previously-treated advanced NSCLC, with a survival benefit observed across all PD-L1 expression levels. Given the need to improve survival for patients with early-stage NSCLC, IMpower010 (NCT02486718), a global Phase III randomized, open-label trial, has been initiated to compare the efficacy and safety of atezolizumab with best supportive care (BSC), following adjuvant cisplatin-based chemotherapy in patients with resected stage IB (tumors ≥4 cm)-IIIA NSCLC. Eligibility criteria include complete tumor resection 4-12 weeks prior to enrollment for pathologic stage IB (tumors ≥4 cm)–IIIA NSCLC. Patients must have adequately recovered from surgery, be eligible to receive cisplatin-based adjuvant chemotherapy and have an ECOG PS 0-1. Exclusion criteria include the presence of other malignancies, use of hormonal cancer or radiation therapy within 5 years, prior chemotherapy, autoimmune disease or exposure to prior immunotherapy. Approximately 1127 patients, regardless of PD-L1 expression status, will be enrolled. Eligible patients will receive up to four 21-day cycles of cisplatin-based chemotherapy (cisplatin [75 mg/m2 IV, day 1] + either vinorelbine [30 mg/m2 IV days 1, 8], docetaxel [75 mg/m2 IV day 1] or gemcitabine [1250 mg/m2 IV days 1, 8], or pemetrexed [500 mg/m2 IV day 1; non-squamous NSCLC only]). Adjuvant radiation therapy is not permitted. Following adjuvant treatment, eligible patients will be randomized 1:1 to receive atezolizumab (1200 mg q3w, 16 cycles) or BSC. Stratification factors will include sex, histology (squamous vs non-squamous), extent of disease (stage IB vs II vs IIIA) and PD-L1 expression by IHC (TC, tumor cell; IC, tumor-infiltrating immune cell; TC2/3 [≥5% expressing PD-L1] and any IC vs TC0/1 [<5%] and IC2/3 [≥5%] vs TC0/1and IC0/1 [<5%]). The primary endpoint is disease-free survival, and secondary endpoints include overall survival and safety. Exploratory endpoints include PD-L1 status, immune and tumor related biomarkers before, during and after treatment with atezolizumab and at radiographic disease occurrence or confirmation of new primary NSCLC. Section not applicable. Section not applicable.