Preliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant ED-SCLC from arm A of the phase II BALTIC study

Abstract

Background: Prognosis in extensive-stage disease small cell lung cancer (ED-SCLC) is poor and patients (pts) commonly relapse within months of completing first-line platinum-based chemotherapy (CT). Investigation into a potential role for immune checkpoint inhibitors in SCLC treatment is supported by good scientific rationale, principally the high mutational burden associated with the disease. We report preliminary efficacy of anti-PD-L1 mAb durvalumab (D) plus anti-CTL4 mAb tremelimumab (T) in pts with platinum-refractory/resistant ED-SCLC, as assessed in Arm A of BALTIC (NCT02937818), a Phase II, multi-arm, signal-searching study. Methods: Eligible pts had ED-SCLC, disease progression (PD) during or within 90 days of completing first-line platinum-based CT, WHO/ECOG performance status 0 or 1, and a life expectancy ≥8 weeks. Pts enrolled in Arm A received D 1500 mg + T 75 mg IV q4w for up to 4 months, followed by D 1500 mg IV q4w monotherapy from Week 16 until PD or discontinuation. The primary endpoint was objective response rate (ORR; investigator assessment, RECIST v1.1). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety and tolerability. Results: 25 pts were enrolled between November 2016 and September 2017, and 21 pts received study treatment (mean age 59.6 years; 71.4% male). As of 02 Feb 2018 (data cut off), median duration of treatment was approximately 14 weeks, with D treatment ongoing in 3 pts and T treatment ongoing in 2 pts. ORR was 9.5% (2 pts; 95% CI 1.17, 30.38). Both were partial responses. 5 pts (23.8%) had stable disease and 1 pt (4.8%) had an unconfirmed partial response. DCR at 12 weeks was 8/21 (38.1%). Grade 3 or higher adverse events (AEs; all cause) occurred in 10 pts (48%), of which 4 pts (19%) experienced an event deemed possibly causally related to treatment by the investigator. 1 pt (4.8%) discontinued due to a possibly causally related AE. Updated ORR, DCR and safety data will be presented, as well as PFS and OS data. Conclusions: D in combination with T demonstrated a tolerable safety profile and encouraging anti-tumour activity in pts with platinum-refractory/resistant ED-SCLC, a difficult-to-treat patient population.