Sutro Biopharma presented expanded data from the dose-optimization portion of its REFRΑME-O1 trial evaluating luveltamab tazevibulin (luvelta) in patients with platinum-resistant ovarian cancer (PROC) at the Society of Gynecologic Oncology (SGO) Annual Meeting in Seattle. The late-breaking oral presentation revealed encouraging antitumor activity across all levels of Folate Receptor-α (FRα) expression of 25% or greater.
Based on the trial results, Sutro has selected an optimized dosing regimen of 5.2 mg/kg plus G-CSF for two cycles, followed by 4.3 mg/kg for subsequent cycles.
Improved Response Rates at Optimized Dose
At the optimized 5.2 mg/kg dose, luvelta achieved an overall response rate (ORR) of 32% and a disease control rate (DCR) of 96%. This represents a significant improvement over the 4.3 mg/kg group, which showed an ORR of 13.8% and a DCR of 69%.
Dr. Jung Yun Lee, Professor and Gynecologic Oncologist at Yonsei Cancer Center and Severance Hospital in South Korea, commented on the findings: "These data demonstrate the potential for improved patient responses compared to standard chemotherapy in PROC, especially patients whose FRα expression falls within the range of at least 25% to less than 75% 2+, which remains an important unmet medical need."
Consistent Efficacy Across FRα Expression Levels
One of the most promising aspects of the data is luvelta's consistent clinical activity across varying levels of FRα expression. In patients with positive staining (PS) 2+ ≥75% (who would be eligible for currently approved FRα-targeting ADCs), the treatment achieved an ORR of 30.8% and a DCR of 100%.
Importantly, in patients with PS2+ <75%, who typically have fewer treatment options, luvelta demonstrated an ORR of 33.3% and a DCR of 91.7%. This suggests potential benefit for a broader patient population than existing therapies.
Safety Profile and Patient Characteristics
The safety profile remained consistent across dosing groups, with no new safety signals observed. Neutropenia, a common side effect of many cancer treatments, was reported to be well-managed. The majority of patients in both dose cohorts had previously received bevacizumab, indicating a heavily pre-treated population.
Mechanism of Action and Development Status
Luvelta (formerly known as STRO-002) is a FRα-targeting antibody-drug conjugate designed using Sutro's cell-free XpressCF® platform. The ADC contains four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver the payload to tumor cells while maintaining systemic stability.
The U.S. Food and Drug Administration has previously granted luvelta Fast Track designation for Ovarian Cancer, as well as Orphan and Rare Pediatric Disease designations for CBF/GLIS2 Pediatric AML.
Future Development Plans
Despite the encouraging clinical data, Sutro Biopharma recently announced it is deprioritizing investment into luvelta's development across all indications. The company is now exploring out-licensing opportunities to continue advancing the treatment for patients with platinum-resistant ovarian cancer and potentially other indications.
"We believe these results demonstrate luvelta's potential to address significant unmet needs in ovarian cancer treatment, particularly for patients with varying levels of FRα expression," said a company representative. "We're committed to finding the right partner to continue developing this promising therapy."
Unmet Need in Platinum-Resistant Ovarian Cancer
Platinum-resistant ovarian cancer represents a significant therapeutic challenge, with limited effective treatment options available. Standard chemotherapy typically yields response rates of 10-15% in this population, highlighting the need for novel approaches.
FRα is overexpressed in approximately 80% of ovarian cancers, making it an attractive target for therapy. However, currently approved FRα-targeting treatments are only indicated for patients with high expression levels, leaving many patients without targeted options.
Luvelta's demonstrated efficacy across a broader range of FRα expression levels could potentially address this gap in care, providing a new option for patients who currently have limited treatment alternatives.
