IMpower132: A phase III clinical program—1L atezolizumab plus platinum-based chemotherapy in chemo-naive advanced non-squamous NSCLC.

Abstract

TPS9101 Background: Platinum-based chemotherapy (chemo) is the current standard of care for patients (pts) with newly diagnosed advanced non-squamous NSCLC. The combination of platinum-based chemo and pemetrexed (pem) provides comparable benefit to pts as other standard platinum doublets commonly used and has a favorable toxicity profile. However, the survival benefit conferred by this combination leaves considerable room for improvement. The anti–PD-L1 mAb atezolizumab (atezo) inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. In the OAK trial, pts with 2L/3L advanced NSCLC had improved mOS in the atezo arm (13.8 mo) vs the docetaxel arm (9.6 mo), with a survival benefit observed across PD-L1 expression levels. The potential for chemo to further augment responses to atezo, with tolerable safety, has also been demonstrated. A global, Phase III, randomized, open-label trial, IMpower132 (NCT02657434), is being conducted to evaluate 1L atezo + platinum-based chemo + pem in chemo-naive pts with stage IV NSCLC. Methods: Eligibility criteria include stage IV NSCLC, measurable disease (RECIST v1.1), no prior chemo and ECOG PS 0-1. Exclusion criteria include tumors known to harbor EGFR or ALK driver mutations, untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Pts will be enrolled regardless of PD-L1 expression status and randomized to the treatment arms. Pts will be stratified by sex, ECOG PS, type of chemo (carboplatin [carbo] vs cisplatin [cis]) and smoking status. Pts will receive four or six 21-day cycles of either atezo + carbo/cis + pem or carbo/cis + pem. Following the induction phase, pts will receive maintenance atezo + pem or pem alone, depending on their allocated treatment regimen. Pts receiving atezo may continue until loss of clinical benefit.Co-primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include IRF-assessed PFS, investigator-assessed ORR and safety. Predictive biomarkers associated with efficacy will be evaluated. Approximately 568 pts will be enrolled. Clinical trial information: NCT02657434.