Phase 1 dose-escalation study of STRO-002, an antifolate receptor alpha (FRα) antibody drug conjugate (ADC), in patients with advanced, progressive platinum-resistant/refractory epithelial ovarian cancer (EOC).
Authors: Naumann R. Wendel , Braiteh Fadi S. , Martin Lainie P. , Hamilton Erika P. , Diaz John Paul , Diab Sami , Schilder Russell J. , Moroney John William , Uyar Denise , O'Malley David M. , Penson Richard T. , DiLea Clifford , Palumbo Michael , De Almeida Venita I. , Matheny Shannon L. , Lu Lin , Berman Craig Jerome , Molina Arturo 
Published: June 2021

5550 Background: STRO-002-GM1 is a Phase 1, open-label study in patients (pts) with advanced, platinum resistant or refractory EOC. STRO-002 is a novel FRα-targeting ADC with a precise DAR of 4 using site-specific conjugation technology to circumvent limitations of current ADCs. STRO-002 induces immunogenic cell death and contains the tubulin-targeting 3-aminophenyl hemiasterlin warhead SC209, a potent cytotoxin that is a weak substrate for P-gp. Methods: STRO-002 is given IV on Day 1 of each 21-day cycle until disease progression. Ocular exams are performed at baseline and every other cycle. Prophylactic corticosteroid eyedrops are not administered. FRα expression was not required for eligibility and retrospective analysis of FRα expression in archival tumor tissue is ongoing. Results: Enrollment has been completed with 39 pts treated at 9 dose levels (0.5 to 6.4 mg/kg). Data cut-off is Jan 30, 2021. Median age was 61 years (range 48-79). Median number of prior systemic therapies was 6 (range 2-11). 86% of treatment emergent adverse events (AEs) were Grade 1-2. The most common treatment related Grade 3 and 4 AEs were reversible neutrophil count decreased (36%) and neutropenia (33%), Grade 3 arthralgia (12.8%) and neuropathy (7.7%). Two pts developed neutropenic fever that resolved with antibiotic therapy. 34 pts were treated at clinically active doses (≥ 2.9 mg/kg) and 31/34 are evaluable for RECIST 1.1 response. Objective responses were seen in 10/31 pts - 1 CR, 4 confirmed PR, and 5 unconfirmed PR (imaging studies under review in 1 pt with uPR). Disease control rate (CR+PR+SD) is 74% at ≥ 12 weeks and 61% at ≥ 16 weeks. 5 pts remain on treatment with 3 ongoing at > 74 weeks. FRα-expression results are available in 14 pts treated at ≥ 2.9 mg/kg with 50% low, 21% medium and 29% high FRα-expressing tumors per PS2+ scoring algorithm. 12/13 pts with H-scores of ≥ 105 achieved disease control with PR or SD. Maximum plasma concentrations of STRO-002 were achieved at the end of the 1 hour infusion and exposure increased in an apparent dose proportionate/linear manner. Conclusions: STRO-002 is a novel FRα-targeting ADC with an encouraging emerging safety and efficacy profile in heavily pretreated relapsed/refractory EOC. No ocular toxicity signals have been observed. Durable responses and anti-tumor activity have been demonstrated across a broad range of FRα expression levels in evaluable pts treated at ≥ 2.9 mg/kg. 48% (15/31) of pts were on treatment without disease progression for ≥ 24 weeks and 13% (4/31) remain on treatment for over a year, suggesting that STRO-002 is well tolerated in long-term responding patients. A randomized expansion cohort comparing STRO-002 at 4.3 mg/kg vs 5.2 mg/kg dose levels in less heavily pretreated EOC pts is ongoing. Clinical trial information: NCT03748186.