Data from the phase 2 portion of the REFRΑME-O1 trial presented at the 2025 SGO Annual Meeting on Women's Cancer revealed that luveltamab tazevibulin generated significant responses in patients with folate receptor alpha (FRα)–positive platinum-resistant ovarian cancer, including those with low to medium expression levels.
The antibody-drug conjugate (ADC) demonstrated an overall response rate (ORR) of 32% (95% CI, 17%-50%) and an impressive disease control rate (DCR) of 96% (95% CI, 80%-99.9%) in patients treated with 5.2 mg/kg plus prophylactic granulocyte–colony stimulating factor (G-CSF) for the first 2 cycles, followed by 4.3 mg/kg. Best responses included complete response (4.0%), partial response (28.0%), stable disease (68.0%), and progressive disease (4.0%).
Notably, the efficacy was consistent across FRα expression levels. Patients with low-to-medium FRα expression (25% to <75%) achieved an ORR of 33.3% and a DCR of 91.7%, comparable to those with high FRα expression (≥75%) who had an ORR of 30.8% and a DCR of 100%.
"[Luveltamab tazevibulin] demonstrated clinical activity with an ORR over 30% in patients with platinum-resistant ovarian cancer and an FRα expression greater than 25% by tumor proportion score, which comprises 80% of all high-grade serous carcinoma," said lead study author Jung-Yun Lee, MD, PhD, associate professor in the Department of Obstetrics and Gynecology at Yonsei University College of Medicine in Seoul, South Korea.
Trial Design and Patient Characteristics
REFRΑME-O1 is a phase 2/3 trial currently enrolling patients for the phase 3 portion, where participants are being randomly assigned 1:1 to receive luveltamab tazevibulin or investigator's choice of chemotherapy.
In the phase 2 portion, investigators enrolled patients with platinum-resistant ovarian cancer who had an FRα expression of at least 25% at any staining intensity. Patients were required to have received one to three prior lines of therapy and have an ECOG performance status of 0 or 1. Those with primary platinum-refractory disease were excluded.
Patients were randomized 1:1 to receive luveltamab tazevibulin at either 5.2 mg/kg with prophylactic G-CSF for the first 2 cycles followed by 4.3 mg/kg in subsequent cycles, or at a consistent 4.3 mg/kg starting from cycle 1. All treatments were administered once every 3 weeks.
The baseline characteristics were well balanced between the two arms. The median age was 60.5 years in the 5.2-mg/kg cohort (n = 28) and 59.0 years in the 4.3-mg/kg cohort (n = 29). Most patients had an ECOG performance status of 0, received prior bevacizumab (Avastin), received a prior PARP inhibitor, and had an FRα expression of at least 75%. Patients in both arms received a median of 2 prior lines of therapy.
Safety Profile and Dose Selection
The safety profile of luveltamab tazevibulin was similar between the two doses. All patients experienced at least one treatment-emergent adverse event (TEAE), with 71.9% experiencing grade 3 or higher TEAEs.
The most common TEAEs included arthralgia (70.2%), nausea (61.4%), constipation (54.4%), neutropenia (45.6%), fatigue (45.6%), and myalgia (43.9%). Notably, rates of neutropenia were lower compared with prior studies following updated management and G-CSF prophylaxis guidelines.
Based on the phase 2 data, researchers selected the optimized dose of luveltamab tazevibulin as 5.2 mg/kg once every 3 weeks plus G-CSF prophylaxis for the first 2 cycles, then 4.3 mg/kg once every 3 weeks for the ongoing phase 3 portion of the trial.
Emerging Landscape of FRα-Targeted Therapies
The positive results from the REFRΑME-O1 trial add to the growing evidence supporting FRα-targeted therapies in ovarian cancer. At the same 2025 SGO Annual Meeting, Elizabeth K. Lee, MD, a medical oncologist at Dana-Farber, presented findings from the RAINFOL-01 study evaluating another FRα-directed antibody-drug conjugate, rinatabart sesutecan (Rina-S).
In this phase 1/2 study of heavily pretreated advanced ovarian cancer patients, Rina-S demonstrated confirmed objective response rates of 22.7% at the 100 mg/m² dose and 55.6% at the 120 mg/m² dose, with two complete responses observed in the higher dose group. Side effects included low blood counts and gastrointestinal distress.
"Rina-S, a novel FRα-directed antibody drug conjugate, demonstrated encouraging activity in patients with ovarian cancer, across FRα expression levels," said Dr. Lee. "These findings support the further study of Rina-S in ovarian cancer."
Clinical Implications
Ovarian cancer remains the fifth leading cause of cancer-related mortality in women, with most patients presenting with advanced disease at diagnosis. Platinum-resistant ovarian cancer represents a significant therapeutic challenge with limited effective treatment options.
The emergence of FRα-targeted ADCs like luveltamab tazevibulin and rinatabart sesutecan offers new hope for these patients. Particularly encouraging is the efficacy observed across different FRα expression levels, potentially expanding the population of patients who might benefit from these therapies.
The ongoing phase 3 portion of the REFRΑME-O1 trial will provide more definitive evidence on the efficacy of luveltamab tazevibulin compared to standard chemotherapy. Similarly, enrollment is ongoing in the phase 2 RAINFOL-OV1 study and the randomized phase 3 RAINFOL-OV2/GOG-3107 trial for Rina-S in platinum-resistant ovarian cancer.
These developments represent significant progress in the treatment landscape for patients with platinum-resistant ovarian cancer, potentially offering more effective and targeted therapeutic options in the near future.
