STRO-002-GM2: A phase 1, open-label, safety, pharmacokinetic, and preliminary efficacy study of STRO-002, an anti-folate receptor alpha (FolRα) antibody-drug conjugate (ADC), in combination with bevacizumab in patients with advanced epithelial ovarian cancer (EOC, including fallopian tube or primary peritoneal cancers).
Authors: Naumann R. Wendel , Martin Lainie P. , Oaknin Ana , Spira Alexander I. , Hamilton Erika P. , Schilder Russell J. , Lu Lin , Kuriakose Jason , Berman Craig Jerome , Molina Arturo 
Published: June 2022

TPS5622 Background: STRO-002 is a novel FolRα targeting ADC, generated using cell-free antibody production and site-specific conjugation technology. STRO-002 demonstrates potent in vitro cytotoxicity in EOC cell lines and anti-tumor activity in xenograft models, including induction of immunogenic cell death. STRO-002 is currently being studied as a single agent in ovarian and endometrial cancer (Phase 1 Study STRO-002-GM1; NCT03748186). Preliminary efficacy data in relapsed/progressive platinum resistant EOC compared favorably to standard chemotherapy (Naumann W., et al, ASCO 2021). Pre-clinical models tested with STRO-002/bevacizumab combinations demonstrated additive anti-tumor activity compared to monotherapy. This study is a first in human study of STRO-002 plus bevacizumab in patients with advanced ovarian cancer that have progressed on standard therapy. Methods: STRO-002-GM2 is a Phase 1, open-label, multicenter, dose escalation study with a standard 3+3 design with a 21-day dose-limiting toxicity (DLT) assessment period followed by dose expansion. The study will assess safety, establish recommended phase 2 dose (RP2D), and preliminary efficacy of STRO-002/bevacizumab combination in patients with recurrent high-grade EOC. Bevacizumab will be administered at the labeled dose of 15 mg/kg given with STRO-002 starting at 3.5 mg/kg, both administered IV q 3 weeks. Planned dose escalation doses of STRO-002 include 3.5, 4.3, and 5.2 mg/kg and will continue until MTD/MAD is reached. Additional intermediate dose level cohorts may be added for RP2D optimization. Once a cohort is cleared per dose escalation rules, up to 10 additional subjects may be enrolled and treated at that cleared dose level in order to obtain additional safety and efficacy data for RP2D determination and ungating of the expansion stage. Dose expansion will enroll approximately 40 patients treated at the RP2D. The patient population is relapsed high-grade EOC with up to 4 prior regimens. Subjects with primary platinum refractory disease will be enrolled in dose escalation only. Key inclusion criteria include: measurable disease, adequate bone marrow and renal function. Key exclusion criteria include: contraindication to receive bevacizumab and prior treatment with a FolRα ADC or ADC containing a tubulin inhibitor. Efficacy evaluation is per RECIST v1.1. Tumor tissue (archival or fresh biopsy) is required. Study oversight includes a Safety Evaluation Team. Samples will be collected to assess the PK and immunogenicity. No formal statistical hypothesis testing will be conducted in this study. This study is currently open for enrollment in the U.S. Clinical trial information: NCT05200364.