Data from Sutro Biopharma’s dose-escalation cohort of the Phase 1 study of STRO-002, a folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) for patients with advanced, progressive ovarian cancer were presented as a poster at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting to be held on June 4-8, 2021.

STRO-002-GM1 is an open-label, multi-center, and two-part single-arm monotherapy Phase 1 study for STRO-002 in patients with advanced, progressive epithelial ovarian cancer, not pre-selected based on FolRα-expression levels. The phase 1 is intended to study the safety, pharmacokinetics, and preliminary efficacy of STRO-002, a folate receptor alpha (FolRα)-targeting ADC. The dose-escalation cohort has enrolled 39 patients and completed enrollment as of August 2020. The dose-expansion cohort is open for enrollment and requires tissue from patients for biomarker analysis prior to enrollment.

“We are pleased to share the maturing dose-escalation data on STRO-002 presented by principal investigator R. Wendel Naumann, MD, Professor & Director of Gynecologic Oncology Research at Levine Cancer Institute, Atrium Health at the 2021 ASCO Annual Meeting,” said Bill Newell, Chief Executive Officer of Sutro Biopharma.

“The 39 patients with advanced, progressive ovarian cancer on the study achieved a median progression-free survival of 7.2 months. Median duration of response was 5.8 months in the five confirmed responders. The dose-escalation data positions STRO-002 as a potentially important treatment option providing durable clinical benefit, especially when compared to standard of care and other agents in clinical development,” Newell added.

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Summary of the Dose-Escalation Cohort Update
The dose-escalation cohort enrolled patients with advanced, progressive epithelial ovarian cancer, not pre-selected based on FolRα-expression levels. Patient enrolled were heavily pre-treated and had received a median of six prior lines of therapy – including at least one platinum-based regimen in 100% of patients, and at least three prior lines of platinum regimens in 46%, bevacizumab in 82%, PARP inhibitors in 59%, checkpoint inhibitors in 21%, and other investigational agents in 36% of patients.

The cohort enrolled 39 patients and included 34 patients treated with clinically active dose levels at 2.9 mg/kg or higher, of which 31 patients had at least one post-baseline scan and were evaluable for RECIST responses. The cohort completed enrollment in August 2020 and the data in the ASCO 2021 abstract was based on an earlier cut-off date of January 30, 2021. The data includes:

  • Of the 31 patients evaluable for RECIST, 10 patients met the criteria for response. One patient achieved a complete response (CR) and nine patients achieved a partial response (PR). Of the nine PRs, four were confirmed PRs (cPRs) and five were unconfirmed PRs (uPRs).
  • For the five confirmed responders (1 CR and 4 cPRs), the median duration of response (DOR) was 5.8 months (95% CI: 2.0, not evaluable).
  • Median study follow-up was 8.4 months and median progression-free survival (PFS) was 7.2 months (95% CI: 4.5, 10.8).
  • 86% of treatment-emergent adverse events (AEs) were Grade 1 or 2. The most common Grade 3 and 4 AEs were neutropenia (64%), arthralgia (13%), fatigue (10%), neuropathy (8%), and abdominal pain (8%), all of which were managed with standard medical treatment, dose reductions, or dose delays.
  • Dose-limiting toxicities (DLTs) were observed at higher dose levels in two patients – at 6.0 mg/kg (Grade 2 neuropathy/Grade 3 arthralgia) and at 6.4 mg/kg (Grade 3 bone pain).

Tissue samples for FolRα-expression analysis were provided by clinical sites retrospectively and were available in 18 patients treated at ≥ 2.9 mg/kg in the dose-escalation cohort. Antitumor activity was observed across a broad range of FolRα-expression levels.

The results of the study confirmed durable responses and anti-tumor activity demonstrated across a broad range of FRα expression levels in evaluable patients treated at ≥ 2.9 mg/kg. 48% (15/31) of patients 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. No ocular toxicity signals were observed.

A randomized expansion cohort comparing STRO-002 at 4.3 mg/kg vs 5.2 mg/kg dose levels in less heavily pretreated patients with advanced, progressive ovarian cancer is ongoing.

Encouraging
“It is encouraging to see the durable clinical benefit in our dose-escalation cohort, including in patients with lower levels of FolRα-expression who are being excluded from other ovarian cancer clinical trials,” noted  Arturo Molina, MD, MS., Chief Medical Officer of Sutro.

“The need for new treatment options for this community drives our efforts to potentially bring STRO-002 to the broadest patient population that may benefit from the therapy. In consideration of a potential FolRα biomarker enrichment strategy, we plan to take a data-driven approach through balancing an efficient path forward, while serving the high unmet medical needs for ovarian cancer patients,” Molina concluded.

Clinical trials
Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers – NCT03748186

Reference
[1] Naumann RW, Braiteh FS, Martin LP, Hamilton EP, Diaz JP, Diab S, Schilder RJ, Moroney JW, et al. 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). Abstract: 5550; Presented at: American Society of Clinical Oncology (ASCO), held June 4 – 8, 2021.J Clin Oncol 39, 2021 (suppl 15; abstr 5550).

Featured image: ASCO before COVID-19 – Attendees during the Plenary Session at the American Society for Clinical Oncology (ASCO). Photo Courtesy: © 2021 ASCO/Scott Morgan. Used with permission.

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