Sutro Biopharma's luveltamab tazevibulin (luvelta) has shown promising results in the dose-optimization portion (Part 1) of the REFRαME-O1 trial for patients with platinum-resistant ovarian cancer (PROC). The data, announced December 10, 2024, highlights a 32% objective response rate (ORR) in evaluable patients at the selected 5.2 mg/kg starting dose, which will be used in the randomized portion (Part 2) of the ongoing registrational trial. These findings suggest luvelta could offer a significant clinical benefit for women with late-stage ovarian cancer.
REFRαME-O1 Trial: Part 1 Results
The REFRαME-O1 trial (Part 1) evaluated luvelta in PROC patients with varying Folate Receptor Alpha (FRα) expression levels, including those with ≥25% Tumor Proportion Score (TPS). Patients were randomized 1:1 to either a 5.2 mg/kg dose with prophylactic pegfilgrastim (G-CSF) for two cycles followed by 4.3 mg/kg for subsequent cycles, or a 4.3 mg/kg dose for all cycles. The primary endpoint was objective response rate (ORR).
Key findings from the 5.2 mg/kg group (N = 25) include:
- An objective response rate (ORR) of 32%, including one confirmed partial response.
- A disease control rate of 96%.
- Approximately half of the patients were ineligible for approved FRα-targeting ADCs.
- 88% of patients had prior bevacizumab treatment.
- Grade 3 or higher neutropenia occurred in 32% of patients, with no febrile neutropenia reported.
Clinical Significance and Expert Commentary
"The clinical results from Part 1 of REFRαME-O1 provide compelling evidence that luvelta has the potential to be both first in class and best in class for patients who have low to medium expression of FRα. FRα is a validated target, and luvelta has the opportunity to reach more patients in need," said Bradley Monk, M.D., Florida Cancer Specialists and Research Institute; Director GOG Partners.
Wendel Naumann, M.D., Professor, Levine Cancer, Atrium Health/Wake Forest University, Charlotte, NC, added, "The topline safety profile of luvelta from Part 1 is encouraging. Neutropenia rates were low, highlighting successful management guidelines. Furthermore, the lack of serious ocular damage, pancytopenia, or Interstitial Lung Disease provide further confidence in our ability to treat a broad group of women with PROC with a focus on their overall wellbeing."
REFRαME-O1: Part 2 and Future Directions
REFRαME-O1 (Part 2) is an ongoing global registrational trial evaluating a 5.2 mg/kg dose of luvelta with prophylactic pegfilgrastim (G-CSF) for the first two cycles, followed by 4.3 mg/kg for subsequent cycles. Part 2 will enroll approximately 500 patients, randomized 1:1 to luvelta or investigator's choice of chemotherapy. Sutro Biopharma is positioning luvelta for an Accelerated Approval application in mid-2027.
About Luveltamab Tazevibulin
Luveltamab tazevibulin (luvelta), formerly known as STRO-002, is an antibody-drug conjugate (ADC) targeting FRα. It is designed to treat a broad range of ovarian cancer patients, including those with lower FRα expression who are not eligible for existing FRα-targeted therapies. Luvelta, developed using Sutro's XpressCF® platform, is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned for efficient tumor delivery and systemic stability.
