CA184-156: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) plus etoposide/platinum (EP) versus placebo plus EP in patients (Pts) with newly diagnosed extensive-stage disease small cell lung cancer (ED-SCLC).

Abstract

TPS7608 Background: Phase III studies have not reported improvement for ED-SCLC beyond EP. Moreover, chemotherapeutic response in SCLC is short-lived, with a median survival of 8–12 months and 5-year survival rates ranging from 1%–2%. Ipi, a fully human monoclonal antibody which binds CTLA-4, augments antitumor immune responses and may potentially improve the clinical benefit of EP. A randomized phase II study of Ipi + paclitaxel/carboplatin (PC) in pts with ED-SCLC showed significant improvement in progression-free survival (PFS) [measured by immune-related response criteria (irRC)] over PC in pts receiving phased Ipi + PC; irRC were derived from WHO criteria to better capture response patterns observed with Ipi. Addition of Ipi trended toward prolonged overall survival (OS) and did not exacerbate PC toxicity; immune-related adverse events were managed using protocol-specific guidelines. This global (~227 sites among 34 countries), multicenter phase III study in pts with ED-SCLC (ClinicalTrials.gov identifier NCT01450761) will determine if adding Ipi to EP increases OS vs EP alone. Methods: Pts with first-line ED-SCLC and ECOG 0-1 will be eligible; pts with a history of autoimmune disease will be ineligible. Pts will be randomized (1:1 to either Arm A or Arm B) to 2 cycles of EP (etoposide [100 mg/m2, IV on Days 1-3 Q3W] and cisplatin [75 mg/m2, IV] or carboplatin [AUC=5, IV] once Q3W), followed by 4 cycles of blinded study drug (Ipi 10 mg/kg, IV in Arm A or placebo in Arm B, Q3W) with 2 concurrent cycles (during cycles 3-4) of EP and Ipi (6 cycles of total therapy). Eligible pts will receive Ipi maintenance therapy Q12W until disease progression or unacceptable toxicity; pts with a complete response will also be eligible for prophylactic cranial irradiation at investigator’s discretion. The primary endpoint is OS; secondary endpoints include OS among pts who receive blinded therapy, immune-related and mWHO PFS, best overall response rate, and duration of response. The trial will also characterize safety, and is estimated to enroll 1100 pts. Clinical trial information: NCT01450761.