Ph1/2 study of Rova-T in combination with nivolumab (Nivo) ± ipilimumab (Ipi) for patients (pts) with 2L+ extensive-stage (ED) SCLC.

Abstract

8516 Background: Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3, a Notch ligand expressed in SCLC but not normal tissue. Nivo ± Ipi has activity in 2L+ SCLC. Preliminary data suggest Rova-T may result in immunogenic cell death, complementing effects of Nivo ± Ipi. Methods: Eligibility: DLL3 expression (DLT phase only), progression after ≥1 line of therapy including a platinum-based regimen; ECOG 0-1; no prior immunotherapy. All pts received 0.3 mg/kg Rova-T IV on Day 1 of two 6-wk cycles. Cohort 1 (C1) also received two 3-wk cycles of 360 mg Nivo beginning on wk 4. Cohort 2 (C2) received four 3-wk cycles of 1 mg/kg Nivo and 1 mg/kg Ipi beginning on wk 4. Both cohorts then received 480 mg Nivo q4wks until PD. Primary objective: safety. Secondary: antitumor activity by RECISTv1.1, OS. Exploratory: PK. Results: As of Sep 7, 2018, 30 pts were dosed in C1 and 12 in C2. 55% were DLL3 high (≥75% DLL3 expression). 28 (67%) completed 2 planned cycles of Rova-T. 4 pts (1 in C1, 3 in C2) experienced DLTs including rash (3), pneumonitis (1) and colitis (1). C1 completed recruitment, and C2 enrollment was stopped after DLT evaluation phase. Preliminary PK showed Nivo±Ipi had no substantial effect on Rova-T exposure. Clinical trial information: NCT03026166. Conclusions: Despite activity in 2L+ ED-SCLC, Rova-T with Nivo/Ipi is not appropriate due to DLTs. Rova-T/Nivo demonstrated some durable responses; however, the safety data suggest that optimization of dose and schedule is warranted. NCT03026166.[Table: see text]