4773 - A phase 1 study evaluating rovalpituzumab tesirine (ROVA-T) in frontline treatment of patients (pts) with extensive stage small cell lung cancer (ES-SCLC)

Background

ROVA-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.

Methods

Pts with ES-SCLC (≥18 yr; 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 0.2 mg/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.

Results

As of March 2019, 26 pts were dosed: Co1 (4), Co2 (5), Co3 (14), Co4 (3). Median age: 66 yr (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 (0.2 mg/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 (0.1 mg), neutropenia and fatigue (62.5% each); Co3 (0.2 mg), fatigue (83.3%); Co4, fatigue, neutropenia, and anemia (100% each). See table for efficacy data. Biomarker DLL3 response data are pending.Table: 1739O

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.

Conclusions

The safety profile of ROVA-T 0.3 mg/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 0.2 mg/kg. There was no clear evidence benefit of addition of ROVA-T to CE.

Clinical trial identification

NCT02819999.

Editorial acknowledgement

Mary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, funded by AbbVie.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

C. 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.