Safety and clinical activity of durvalumab in combination with tremelimumab in extensive disease small-cell lung cancer (ED-SCLC).

8517 Background: Treatment options for ED-SCLC are limited, with standard first-line platinum and etoposide and second-line topotecan having limited clinical activity. Beyond these agents, no approved therapy prolongs survival. Dual checkpoint inhibition with the anti-PD-L1 durvalumab in combination with the anti-CTLA-4 tremelimumab has demonstrated a manageable safety profile and clinical activity in several solid tumor types. Here we present safety and clinical activity data for the combination in pretreated patients with ED-SCLC. Methods: In this phase 1 dose-exploration and expansion study, patients with ECOG PS 0–1 received durvalumab 20 mg/kg every 4 wks in combination with tremelimumab 1 mg/kg every 4 wks for 7 doses, then every 12 wks for 2 doses, followed by durvalumab 10 mg/kg every 2 wks for up to 12 mos, with retreatment permitted for progression after 12 mos of therapy. Antitumor activity was evaluated by investigator-assessed RECIST v1.1. Results: As of 20 Oct 2017, 30 patients (median age 63.5 y, 57% male, 70% ECOG PS 1) received treatment in the expansion phase. All patients had prior systemic therapy (median 2 prior therapies); 19 patients were platinum resistant/refractory. 20 patients (67%) reported ≥1 treatment-related AE (TRAE); the most common were fatigue (n = 7 23%) and pruritus (n = 7 23%). 7 patients (23%) had grade 3/4 TRAEs. No patients discontinued due to TRAEs and there were no treatment-related deaths. Confirmed ORR was 13.3% (2 CR, 2 PR; 95% CI 3.8–30.7), including 3 platinum resistant/refractory patients (1 CR with 2 prior therapies, 2 PR each with 1 prior treatment); median duration of response was 18.9 mos (95% CI 16.3–18.9). Disease control rate at 16 wks was 20.0% (95% CI 7.7–38.6). Median PFS was 1.8 mos (95% CI 1.0–1.9), median OS was 7.9 mos (95% CI 3.2–15.8), and 12-mo OS rate was 41.7% (95% CI 23.3–59.2). In addition, one patient with a brain metastasis was continuing in follow-up > 2 years after starting treatment. Conclusions: Durvalumab in combination with tremelimumab had a tolerable safety profile and promising activity in pretreated ED-SCLC. Responses were durable and seen in both platinum-sensitive and platinum resistant/refractory patients. Clinical trial information: NCT02261220.