1739O - A phase I study evaluating rovalpituzumab tesirine (ROVA-T) in frontline treatment of patients (pts) with extensive stage small cell lung cancer (ES-SCLC)

Abstract

BackgroundROVA-T is an antibody-drug conjugate targeting delta-like protein 3 (DLL3) that is highly expressed in 80% of SCLC. The reported study (NCT02819999) evaluated ROVA-T alone or in combination with platinum-based chemotherapy (CE) in frontline treatment of ES-SCLC. MethodsPts with ES-SCLC (≥18yr; ECOG PS: 0–1) received 1 cycle of CE prior to enrollment (prior treated CNS lesions allowed; tissue banked for later DLL3 analysis). Four cohorts (Co) were enrolled: single-agent ROVA-T (Co1); ROVA-T induction followed by CE (Co2); ROVA-T + CE (Co3); ROVA-T maintenance after CE (Co4). Co1, 2, and 4 were closed early. Co3 received a total 2 IV doses of ROVA-T (0.1 or 0.2mg/kg) on day 1 of each 6-wk cycle in combination with 4 doses of CE. Primary objectives of Co3: determine the recommended phase II dose (RP2D), evaluate safety and preliminary efficacy; toxicity was graded per NCI CTCAE v4.3, efficacy assessed via RECIST 1.1.Table: 1739OTable: 1739OCohort 2 (0.3mg/kg) n=5Cohort 3Cohort 4 (0.3mg/kg) n=3Total† N=260.1mg/kg n=80.2mg/kg* n=6Objective response rate, n (%) [95% CI]‡2 (40.0) [5.3–85.3]5 (62.5) [24.5–91.5]2 (33.3) [4.3–77.7]1 (33.3) [0.8–90.6]10 (38.5) [20.2–59.4]Complete response, n (%)0 (0.0)1 (12.5)0 (0.0)0 (0.0)1 (3.8)Partial response, n (%)2 (40.0)4 (50.0)2 (33.3)1 (33.3)9 (34.6)Median PFS, mo [95% CI]2.3 [0.7-NR]4.0 [1.6–5.7]4.2 [2.3-NR]4.2 [0.7–4.2]3.9 [2.0–4.2]Duration of response, mo Median [95% CI]2.7 [0.5- NR]3.5 [1.8–5.8]2.9 [2.8-NR ]1.7 [NR–NR]2.8 [1.7–5.8]*Best overall response rate: 66.7% (2 out of 6 patients had an unconfirmed response).†Cohort 1 (n=4): One response observed.‡Response is according to RECIST 1.1. Confirmation of CR and PR is required, and changes in tumor measurements must be confirmed by repeat assessment performed no less than 4 weeks (28 days) from initial assessment. CI, confidence interval; CR, complete response; NR, not reached; PFS, progression-free survival; PR, partial response. ResultsAs of March 2019, 26 pts were dosed: Co1 (4), Co2 (5), Co3 (14), Co4 (3). Median age: 66yr (46% <65, 54% ≥65); 73% ECOG 1; 27% had baseline brain metastases. Fifteen (60%) pts received 2 doses of ROVA-T; 67% completed 4 doses CE. One pt (16.6%) in Co3 (0.2mg/kg) experienced DLT: grade 3 bullous dermatitis. Most common drug-related AEs (ROVA-T or CE) were fatigue (57.7%), anemia (38.5%), and neutropenia (34.6%). Most common drug-related AEs by Co: Co1, nausea, dyspnea, and hypoalbuminemia (50% each); Co2, edema peripheral (60%); Co3 (0.1mg), neutropenia and fatigue (62.5% each); Co3 (0.2mg), fatigue (83.3%); Co4, fatigue, neutropenia, and anemia (100% each). See table for efficacy data. Biomarker DLL3 response data are pending. ConclusionsThe safety profile of ROVA-T 0.3mg/kg monotherapy was challenging, while the tolerability of lower doses of ROVA-T in combination with CE was acceptable. The RP2D for ROVA-T + CE was 0.2mg/kg. There was no clear evidence benefit of addition of ROVA-T to CE. Clinical trial identificationNCT02819999. Editorial acknowledgementMary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, funded by AbbVie. Legal entity responsible for the studyAbbVie Inc. FundingAbbVie Inc. DisclosureC. Hann: Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Ascentage; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Genentech/Roche; Research grant / Funding (institution): Merrimack Pharmaceuticals. T. Burns: Advisory / Consultancy: AbbVie Stemcentrx. A. Dowlati: Advisory / Consultancy: Seattle genetics; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: AbbVie; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Roche; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): BMS. D. Morgensztern: Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Heat Biologics; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: BMS; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): NewLink Genetics; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Stemcentrx; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Baxter; Research grant / Funding (institution): Incyte. M. Koch: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. Y. Chang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. P. Komarnitsky: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. C. Ludwig: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. H. Nimeiri: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. All other authors have declared no conflicts of interest.