Luveltamab Tazevibulin Produces Responses in Platinum-Resistant Ovarian Cancer

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Treatment with the folate receptor alpha (FRα)–targeted antibody-drug conjugate (ADC) luveltamab tazevibulin (luvelta; STRO-002) led to responses at the selected dose for part 2 of the phase 2/3 REFRaME-O1 trial (NCT05870748), according to topline data from the dose-optimization portion (part 1) of the study.¹

Findings showed that evaluable patients treated at a starting dose of 5.2 mg/kg of luvelta (n = 25) achieved an overall response rate (ORR) of 32% and a disease control rate of 96%.

Notably, part 1 of the study included patients with low, medium, and high FRα expression levels, defined as patients with tumor proportion score of at least 25% (at least 25% of tumor cells expressing FRα). Approximately half of the patients treated would have been ineligible for the FDA-approved FRα-targeted ADC mirvetuximab soravtansine-gynx (Elahere), according to a news release from Sutro Biopharma, the developer of luvelta.

Additional data from part 1 will be presented at an upcoming medical meeting.

“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,” Bradley Monk, MD, of the Florida Cancer Specialists and Research Institute and director of GOG Partners, stated in a news release.

REFRaME-O1 is a randomized, multicenter, international, open-label, 2-part trial enrolling patients at least 18 years of age with high-grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.² Patients need to have relapsed disease following a total of 1 to 3 prior lines of therapy; prior treatment with bevacizumab (Avastin) is required, unless contraindicated. Key inclusion criteria consist of positive FRα expression per central testing; an ECOG performance status of 0 or 1; at least 1 measurable target lesion per RECIST 1.1 criteria; and adequate organ function.

Patients are excluded if they have low-grade ovarian carcinoma or clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas; received prior treatment with a FRα-targeted ADC or an ADC containing a tubulin inhibitor; have primary platinum-refractory disease; or underwent prior solid organ transplant.

During part 1 of the study, patients were randomly assigned 1:1 to receive luvelta at a starting dose of 5.2 mg/kg once every 3 weeks in combination with prophylactic pegfilgrastim (G-CSF) for 2 cycles, followed by luvelta at 4.3 mg/kg in subsequent cycles; or luvelta at 4.3 mg/kg once every 3 weeks for all cycles.^1,2 Part 2 of REFRaME-O1 serves as a registrational trial, in which approximately 500 patients will be randomly assigned 1:1 to receive luvelta at the 5.2-mg/kg dose or receive investigator’s choice of chemotherapy consisting of gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or topotecan.²

ORR and progression-free survival are the trial’s primary end points. Secondary end points include overall survival, duration of response, safety, and quality of life.

Among patients treated at the selected dose in part 1 of the study, 88% had received prior bevacizumab.¹ Notably, 32% of patients experienced grade 3 or higher neutropenia, and no instances of febrile neutropenia were reported.

“The topline results confirm luvelta’s favorable safety and efficacy profile at the starting dose of 5.2 mg/kg, further supporting our confidence that it can improve clinical outcomes compared to chemotherapy in our ongoing registrational trial," Anne Borgman, MD, chief medical officer of Sutro Biopharma, added in a news release. “Consistent response rates were observed in patients across all levels of FRα expression of 25% or greater, reconfirming luvelta's potential to expand the benefit of a targeted treatment to 8 out of 10 patients [with platinum-resistant ovarian cancer].”

References

1. Sutro Biopharma announces selected dose for luvelta and topline results from dose-optimization portion of REFRαME-O1 trial in platinum resistant ovarian cancer. News release. Sutro Biopharma. December 10, 2024. Accessed December 10, 2024. https://www.sutrobio.com/sutro-biopharma-announces-selected-dose-for-luvelta-and-topline-results-from-dose-optimization-portion-of-refr%ce%b1me-o1-trial-in-platinum-resistant-ovarian-cancer/
2. REFRaME-O1: a study to investigate the efficacy and safety of luveltamab tazevibulin versus investigator's choice (IC) chemotherapy in women with ovarian cancer (including fallopian tube or primary peritoneal cancers) expressing FOLR1. ClinicalTrials.gov. Updated August 29, 2024. Accessed December 10, 2024. https://clinicaltrials.gov/study/NCT05870748