Abstract CT125: STRO-002-GM1, a first in human, phase 1 study of STRO-002, an anti-folate receptor alpha (FRα) antibody drug conjugate (ADC), in patients with advanced platinum-resistant/refractory epithelial ovarian cancer (OC), including fallopian tube or primary peritoneal cancers
Authors: Naumann R. Wendel , Uyar Denise , Moroney John W. , Braiteh Fadi S. , Schilder Russell J. , Diaz John P. , Hamilton Erika , Diab Sami , Martin Lainie P. , O'Malley David M. , Penson Richard T. , DiLea Clifford , Palumbo Michael , DeAlmeida Venita , Matheny Shannon , Molina Arturo 
Published: September 2020

Abstract
Introduction: FRα is overexpressed in 80% of OC with minimal expression in normal tissues. STRO-002 is a novel FRα-targeting ADC designed to circumvent limitations of current ADCs. STRO-002 was generated with a cell-free antibody production system (XpressCF™) and site-specific conjugation (XpressCF+™) platform. STRO-002 has a DAR of 4 and contains the tubulin-targeting 3-aminophenyl hemiasterlin warhead SC209, a potent cytotoxin that is rapidly cleared and a weak substrate for P-gp efflux pumps. STRO-002 demonstrated potent cytotoxic activity in multiple FRα-positive tumor cell lines and significant efficacy in OC xenograft models. Herein we report the results of our dose escalation study of STRO-002 in patients (pts) with OC. Methods: STRO-002-GM1 is a Phase I, open-label, multicenter, dose escalation study with dose expansion to identify the maximum tolerated dose (MTD), and recommended Phase II dose (RP2D) in pts with advanced, platinum resistant or refractory OC. There is no patient selection based on FRα expression. STRO-002 is given IV on Day 1 of each 21-day cycle (C) until disease progression. Ocular exams are performed at baseline and every other cycle. No prophylactic corticosteroid eye drops are used. Results: 20 pts have been dosed & 18 pts have completed at least 1 cycle of STRO-002 at 7 dose levels: 0.5, 1.0, 1.8, 2.9, 4.3, 5.2 and 6.0 mg/kg. Median age is 60.5 (r, 48-70). Median ECOG status is 0 (r, 0-1). Median # of prior therapies is 6 (r, 2-10). 55% of pts have prior PARP inhibitors, 85% have prior bevacizumab. Median # of STRO-002 cycles is 3 (r, 1-15). One DLT of grade 3 neuropathy was reported at the 6.0 mg/kg dose level. Two patients have experienced grade 4 neutropenia, an expected and reversible side effect of STRO-002 treatment. 92% of AEs are grade 1 or 2. The most common TEAEs in ≥ 30 % of pts includes fatigue, nausea, decreased appetite and dizziness. No ocular findings have been observed. Emerging PK profile: after 1 hour infusion, total antibody concentrations declined in a log-linear manner with a 22-84 h half-life, dose-exposure relationship appeared linear without accumulation after repeat administration. Six pts have discontinued due to disease progression. 14 pts remain on treatment and dose escalation is ongoing. One patient has achieved a confirmed partial response (PR); 2 patients have confirmed stable disease (cSD) at C5, 2 pts have cSD at C7 and 1 pt has cSD at C13; 3 patients have achieved a confirmed CA-125 response. Conclusions: STRO-002 is the first hemiasterlin-containing ADC generated with cell-free protein synthesis technology to be tested in pts with solid tumors. The preliminary safety profile and evidence of efficacy and clinical benefit in the first 20 OC pts treated with STRO-002 is encouraging, particularly in this heavily pre-treated, platinum resistant/refractory patient population. No ocular toxicity signals have been observed. MTD has not been reached. Updated results and the recommended phase 2 dose will be presented. This study is registered with clinicaltrials.gov identifier NCT03748186.
Citation Format: R. Wendel Naumann, Denise Uyar, John W. Moroney, Fadi S. Braiteh, Russell J. Schilder, John P. Diaz, Erika Hamilton, Sami Diab, Lainie P. Martin, David M. O'Malley, Richard T. Penson, Clifford DiLea, Michael Palumbo, Venita DeAlmeida, Shannon Matheny, Arturo Molina. STRO-002-GM1, a first in human, phase 1 study of STRO-002, an anti-folate receptor alpha (FRα) antibody drug conjugate (ADC), in patients with advanced platinum-resistant/refractory epithelial ovarian cancer (OC), including fallopian tube or primary peritoneal cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT125.