Luveltamab Tazevibulin Produces Responses in Platinum-Resistant Ovarian Cancer With Low/Medium FRα Expression

Treatment with the antibody-drug conjugate (ADC) luveltamab tazevibulin generated response with a manageable safety profile in patients with folate receptor alpha (FRα)–positive platinum-resistant ovarian cancer, including those with low to medium expression, according to data from the phase 2/3 REFRαME-O1 trial (NCT05870748).

Data from the phase 2 portion presented at the 2025 SGO Annual Meeting on Women’s Cancer showed that patients treated with luveltamab tazevibulin at 5.2 mg/kg plus prophylactic granulocyte–colony stimulating factor (G-CSF) for the first 2 cycles, then 4.3 mg/kg (n = 25) experienced an overall response rate (ORR) of 32% (95% CI, 17%-50%) and a disease control rate (DCR) of 96% (95% CI, 80%-99.9%). Best responses included complete response (4.0%), partial response (PR; 28.0%), stable disease (SD; 68.0%), and progressive disease (PD; 4.0%). The median time to response was 6.0 weeks (range, 4.7-11).

Notably, in this cohort, patients with low-to-median FRα expression (n = 12), defined as an FRα level of at least 25% and less than 75%, the ORR was 33.3% (95% CI, 12.3%-60.9%) with a DCR of 91.7% (95% CI, 61.5%-99.8%). In those with high FRα expression of at least 75% (n = 13), the ORR and DCR were 30.8% (95% CI, 9.1%-61.4%) and 100% (95% CI, 75.3%-100%), respectively.

Those treated at dose of 4.3 mg/kg in cycle 1 and beyond (n = 29) achieved an ORR of 13.8% (95% CI, 3.9%-32%) and a DCR of 69% (95% CI, 49%-85%). Best responses comprised PR (13.8%), SD (55.2%), and PD (31.0%). The median time to response was 6.4 weeks (range, 5.4-11.9).

“[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,” 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, said in a presentation of the data.

Trial Design

REFRαME-O1 is a phase 2/3 trial that is currently enrolling patients for the phase 3 portion, where patients are being randomly assigned 1:1 to receive luveltamab tazevibulin or investigator’s choice of chemotherapy.

In the phase 2 portion of the study, investigators enrolled patients with platinum-resistant ovarian cancer who had an FRα expression of at least 25% at any staining intensity. One to 3 prior lines of therapy were required, as was an ECOG performance status of 0 or 1. Patients with primary platinum-refractory disease were excluded.

Patients enrolled in phase 2 were randomly assigned 1:1 to receive luveltamab tazevibulin given once every 3 weeks at a starting dose of 5.2 mg/kg with prophylactic G-CSF for the first 2 cycles, then at 4.3 mg/kg in subsequent cycles; or luveltamab tazevibulin at 4.3 mg/kg once every 3 weeks starting in cycle 1.

The primary end points of phase 2 were safety, investigator-assessed ORR per RECIST 1.1 criteria, and pharmacokinetics.

Lee noted that the baseline characteristics were well balanced between the phase 2 arms. The median age was 60.5 years (range, 41-81) in the 5.2-mg/kg cohort (n = 28) and 59.0 years (range, 42-81) in the 4.3-mg/kg cohort (n = 29). The majority of patients had an ECOG performance status of 0 (5.2 mg/kg, 50.0%; 4.3 mg/kg, 58.6%), received prior bevacizumab (Avastin; 89.3%; 79.3%), received a prior PARP inhibitor (53.6%; 55.2%), and had an FRα expression of at least 75% (57.1%; 62.1%). Patients in both arms received a median of 2 prior lines of therapy (range, 1-3).

At data cutoff, 79% of patients in the 5.2-mg/kg cohort had discontinued treatment due to PD (71.4%) and adverse effects (AEs; 3.6%); 86% of patients in the 4.3-mg/kg cohort had discontinued study treatment due to PD (65.5%) and AEs (10.3%).

Safety Data

Lee explained that the safety profile of luveltamab tazevibulin was similar between the 2 doses. Additionally, rates of neutropenia were lower compared with prior studies following updated management and G-CSF prophylaxis guidelines.

In the overall population between both doses (n = 57), all patients experienced at least 1 treatment-emergent AE (TEAE), and 71.9% had grade 3 or higher TEAEs. The most common TEAEs included arthralgia (any-grade, 70.2%; grade ≥3, 12.3%), nausea (61.4%; 3.5%), constipation (54.4%; 7.0%), neutropenia (45.6%; 28.1%), fatigue (45.6%; 3.5%), myalgia (43.9%; 8.8%), abdominal pain (38.6%; 8.8%), neuropathy (38.6%; 1.8%), decreased appetite (38.6%; 0%), vomiting (35.1%; 1.8%), insomnia (29.8%; 3.5%), increased alanine aminotransferase levels (26.3%; 5.3%), and alopecia (24.6%; 0%).

Based on the phase 2 data, the optimized dose of luveltamab tazevibulin was selected 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.

Disclosures: Lee reported giving lectures for AstraZeneca, Eisai, GSK, MSD, Roche, and Takeda; serving in advisory board positions for AstraZeneca, CanariaBio, DS, Eisai, Genmab, GIl, ImmunoGen, Merck, MSD, Seagen, Sutro, and Regeneron; and receiving institutional financial support from Abbvie, Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Daiichi Sankyo, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen. Kelun, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, TORL-bio, Takeda, and Zymeworks.

Reference

Lee J-Y, Oaknin A, Lorusso D, et al. Efficacy and safety of luveltamab tazevibulin in patients with recurrent platinum-resistant ovarian cancer: results from the dose-optimization stage of the REFRαME-O1 (GOG-3086, ENGOT-79OV, and APGOT-OV9) phase 2/3 study. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 922978.