2909 - Preliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant ED-SCLC from Arm A of the Phase II BALTIC study

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.

Clinical trial identification

NCT02937818 (October 5, 2016).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Editorial Acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Paul Glacken, MSc, and Elizabeth Andrew, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

Disclosure

S. Jones: Former employment: AstraZeneca; Consultant, equity owner: AstraZeneca. H. Jiang: Employment, equity ownership: AstraZeneca. N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, MSD, Lilly, Boehringer-Ingelheim outside the submitted work. All other authors have declared no conflicts of interest.