521TiP IMpower133: A phase I/III study of atezolizumab (atezo) with carboplatin (carbo) and etoposide as 1L therapy in patients (pts) with extensive-stage SCLC (ES-SCLC)

Abstract

Background: Platinum-based chemotherapy (chemo) with etoposide is the current first-line (1L) standard of care for the majority of pts with ES-SCLC. Although initial response rates with chemo range from 50% to 70%, survival outcomes remain poor (median OS, <1 year), highlighting the need for new treatments. Atezo, an anti-PD-L1 mAb that prevents the interaction of PD-L1 with its receptors PD-1 and B7.1, restores antitumor T-cell activity and has shown tolerable safety with promising durability of response in pts with ES-SCLC: confirmed ORR was 6% (n=1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n=4/17, with 2 pts on atezo for ≥12 mo). Preliminary data also indicate the potential synergism of atezo with platinum-based chemo in NSCLC, in which durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial was initiated to evaluate the efficacy and safety of 1L atezo + carbo + etoposide compared with placebo+ carbo +etoposide in treatment-naive pts with ES-SCLC. Trial design: Inclusion criteria include ES-SCLC, measurable disease (RECIST v1.1), ECOG PS 0-1 and no prior anticancer treatment. Exclusion criteria include untreated CNS metastases and autoimmune disease. Submission of tumor tissue is a study requirement but not mandatory for entry; pts will be enrolled regardless of biomarker status. Stratification factors include sex, ECOG performance status and presence of brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carbo (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include ORR and DOR. Safety and tolerability will also be assessed; ≈ 400 pts will be enrolled.