Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolR[alpha]) antibody-drug conjugate (ADC), has demonstrated promising safety and efficacy in patients with recurrent epithelial ovarian cancer, according to an update on the STRO-002-GM1 Phase I dose-expansion cohort. Research presented at the 2023 ASCO Annual Meeting aimed to evaluate the effectiveness of luveltamab tazevibulin, a novel ADC targeting FolR[alpha], in a broad distribution of FolR[alpha] expression (Abstract 5508).
Luveltamab tazevibulin, also known as luvelta, is designed with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead, resulting in cytotoxic and immunologic cell death. Using site-specific conjugation technology, luvelta is intended to target a wide range of ovarian cancer cases with FolR[alpha] expression. The global Phase I study, STRO-002-GM1 (NCT03748186), was conducted to assess the safety and efficacy of luvelta in patients with relapsed ovarian cancer.
The analysis included advanced ovarian cancer patients with progressive platinum-resistant or platinum-sensitive disease. Patients were randomly assigned to receive luveltamab at 4.3 or 5.2 mg/kg intravenously every 3 weeks. Prophylactic corticosteroid eye drops were not administered. FolR[alpha] expression was retrospectively analyzed using the FOLR1 IHC assay.
In total, 44 patients were enrolled in the study, with 23 receiving luveltamab at 4.3 mg/kg and 21 receiving the 5.2 mg/kg dose. Among the patients with a FolR[alpha] expression of >25 percent (n=35), the median number of prior lines of therapy was 2.5, with a range of 1 to 3. Additionally, 69 percent of these patients had received prior bevacizumab treatment and 83 percent had received prior PARP inhibitor treatment.
The most common Grade >=3 treatment-emergent adverse events were neutropenia (70.5%), arthralgia (18.2%), and anemia (13.6%). The incidence of Grade 3 or 4 neutropenia was higher in the 5.2 mg/kg group (76% vs. 65%). Febrile neutropenia occurred in one patient at each dose level. TEAEs led to dose delay and reduction, with a higher incidence in the 5.2 mg/kg group. One patient experienced Grade 5 sepsis with Grade 4 neutropenia, but adverse events were successfully managed with standard medical treatment and dose reductions.
For an in-depth analysis on the study, Oncology Times had a conversation with Ana Oaknin, MD, PhD, first author and Head of the Gynecological Tumor Unit and Attending Physician at the Vall d'Hebron University Hospital in Barcelona, as well as principal clinical investigator of the Gynecologic Cancer Unit at the Vall d'Hebron Institute of Oncology.
Oncology Times: What is the efficacy of STRO-002 in patients with recurrent epithelial ovarian cancer, and how does it vary based on FolR[alpha] expression levels?
Oaknin: "Preliminary findings from the STRO-002-GM2 dose-expansion study in recurrent epithelial ovarian cancer demonstrate promising initial efficacy of luveltamab tazevibulin (STRO-002). In the all-comers population, where patients were not specifically selected for FolR[alpha] expression, a 31.7 percent overall response rate (ORR) was observed, along with a median duration of response (DOR) of 5.4 months and a median progression-free survival (PFS) of 4.3 months.
"When focusing on patients with a FolR[alpha] expression level above 25 percent (TPS >25% and regardless of staining intensity), the preliminary efficacy outcomes improved significantly. This subgroup exhibited a 37.5 percent ORR, median DOR of 5.5 months, and median PFS of 6.1 months. Notably, at the higher starting dose level, these patients experienced even higher response rates, with a 43.8 percent ORR, median DOR of 5.4 months, and median PFS of 6.6 months.
"It is worth highlighting that responders were observed across a broad group of patients with FolR[alpha] expression, which accounted for approximately 80 percent of the advanced ovarian cancer population. The ORRs across different FolR[alpha] expression levels were as follows:
* 11.1 percent for FolR[alpha] by TPS <=25 percent, regardless of intensity;
* 33.3 percent for FolR[alpha] by TPS >25 percent to <=75 percent, regardless of intensity; and
* 40 percent for FolR[alpha] by TPS >75 percent, regardless of intensity.
"Additionally, the efficacy of luveltamab tazevibulin was maintained even with dose reductions and, notably, it did not give rise to unwanted ocular and pneumonitis events typically associated with other ADCs. Although there were instances of Grade 3 or higher neutropenia, these cases were uncomplicated, asymptomatic, and resolved spontaneously with dose delays and reductions. Importantly, the discontinuation rates due to adverse events were low.
"These findings signify the potential of luveltamab tazevibulin as a promising therapeutic option for recurrent epithelial ovarian cancer, particularly in patients with lower levels of FolR[alpha] expression who are not well supported by the current standard of care. The preliminary efficacy, durability of response, and favorable safety profile in this study warrant further investigation and potential consideration for future treatment strategies."
Oncology Times: What are the next steps for evaluating the safety and efficacy of STRO-002 in patients with recurrent epithelial ovarian cancer?
Oaknin: "The next steps involve the initiation of the REFRaMe randomized Phase II/III global registration study for evaluating the safety and efficacy of luveltamab tazevibulin (STRO-002) in patients with recurrent epithelial ovarian cancer. This study will specifically enroll women with platinum-resistant ovarian cancer who exhibit a FolR[alpha] expression level above 25 percent as determined by tumor proportion score (TPS), regardless of staining intensity.
"The population of platinum-resistant ovarian cancer patients with FolR[alpha] expression above 25 percent by TPS, regardless of intensity, represents a significant unmet medical need globally, including individuals who do not meet the criteria for current approved treatment with mirvetuximab (FolR[alpha] expression greater than 75 percent and intensity score of PS2+)."
Oncology Times: Are there any plans to investigate the use of STRO-002 in combination with other agents or in earlier stages of ovarian cancer?
Oaknin: "Currently, there are ongoing clinical investigations exploring the potential of luveltamab tazevibulin (STRO-002) in different settings. In one ongoing Phase I study, luveltamab tazevibulin is being evaluated in combination with bevacizumab in patients with recurrent disease following standard platinum-based therapies (NCT05200364).
"Furthermore, within the STRO-002-GM1 trial, there is a Phase I cohort specifically focusing on luveltamab tazevibulin as a monotherapy for patients with endometrial cancer. This cohort aims to assess the safety and potential efficacy of luveltamab tazevibulin in this particular patient population.
"Looking ahead, [there are] plans to expand the exploration of luveltamab tazevibulin in other cancer types that express FolR[alpha], thereby potentially broadening its potential application beyond ovarian and endometrial cancer."
Dibash Kumar Das is a contributing writer.