Treatment with the folate receptor alpha (Frα)-directed antibody-drug conjugate rubertamab tazevibulin (STRO-002; Luvelta) resulted in an overall response rate (ORR) of 37.5% in Frα-selected patients with advanced ovarian cancer and improved tumor efficacy. defined by a percentage. Results from a phase 1 dose escalation study (NCT03748186) show a score of over 25%.1
Results also showed that the drug induced a median duration of response (DOR) of 5.5 months (n = 12) and a median progression-free survival (PFS) of 6.1 months (n = 35), regardless of starting dose. I showed that.
In line with previous safety data, the most common side effect from the dose escalation phase was asymptomatic neutropenia, with no significant ocular toxicity signals or complications reported.
“Today, patients with this type of heavily pretreated ovarian cancer have very limited treatment options available and unfortunately poor outcomes,” said R., professor and director of Gynecologic Oncology Research. He is the Associate Medical Director of Clinical Trials at Atrium Health’s Levine Cancer Institute in Charlotte, North Carolina and Co-Principal Investigator of the STRO-002-GM1 study.
“To date, luvelta continues to show encouraging efficacy data, which is further supported by results from the dose expansion cohort,” he added. “The safety profile was shown to be manageable across a broad spectrum of FolRα-selected ovarian cancer patients, particularly in the absence of ocular complications.”
Frα-selected patients account for approximately 80% of all advanced ovarian cancer patients, making Frα an ideal target for treatment selection and evaluation.
A modified 3+3 dose escalation study with a dose escalation phase was employed in this study.2 In the dose escalation phase, patients with relapsed/refractory advanced ovarian cancer were enrolled on standard of care. Patients with ovarian and endometrial cancer were enrolled in the dose expansion portion.
The Ovarian Cancer Expansion Cohort (Cohort A) consisted of a randomized, dose-finding design to two dose levels of STRO-002 (4.3 mg/kg and 5.2 mg/kg). Dose escalation in the endometrial cancer population (Cohort B) includes a single dose cohort design of STRO-002 at 5.2 mg/kg. Thirty-two FolRα-selected patients, defined as a tumor proportion score (TPS) greater than 25%, were included in the findings.
Additional findings from the phase 1 trial were FRα TPS ≤25%, median DOR of 2.9 months (n = 1), and median PFS of 3.8 months (n = 9).
Furthermore, a higher starting dose of 5.2 mg/kg provided greater benefit compared to a lower dose of 4.3 mg/kg in Frα-selected patients. At the high dose, ORR was 43.8% (n = 16) and median DOR and PFS were 5.4 months (n = 7) and 6.6 months (n = 16), respectively. In the low-dose cohort, ORR, median DOR, and PFS were 31.3% (n = 16), 13 months (n = 5), and 6.1 months (n = 19), respectively.
In Cohort C, 15 additional patients with advanced ovarian cancer were enrolled and received pegfilgrastim prophylaxis on day 8 after each dose of rubertamab tazevibulin 5.2 mg/kg. Of her 10 patients for whom safety could be evaluated, a significant reduction in neutropenia and a potential increase in dosing intensity due to reduced dosing delays were reported.
Specifically, grade 3 or greater neutropenia decreased from 66.7% to 10.0%.P. = .006). In addition, there was a 60.6% reduction in dose delay in his second cycle of treatment (P. = .021).
Based on these results, agent developer Sutro plans to initiate a phase 2/3 REFRaME trial for enrollment in the second quarter of 2023.
In the dose confirmation phase of REFRaME, 50 patients were randomized 1:1 to receive 2 cycles of rubertamab tazevibulin 5.2 mg/kg and prophylactic pegfilgrastim, followed by escalation to 4.3 mg/kg. is reduced to 4.3 mg/kg of rubertamab tazevibulin alone.
After this part of the study, additional patients will be randomly assigned to two dose levels and standard chemotherapy. Other dose levels will be reduced based on agreement with the FDA regarding recommended dose and standard of care. After the trial accumulates data on approximately 110 patients who received the recommended dose of rubertamabutazevibrin, Sutro plans to apply for accelerated approval based on her ORR primary endpoint.
After completion of the Phase 3 portion of the study, the company may seek full approval based on the primary endpoint of PFS between the rubertamab tazevibulin arm (n = 160) and the standard of care arm (n = 160) .
Sutro CEO Bill Newell said: “The addition of cohort C allowed us to evaluate patients who were treated with prophylactic pegfilgrastim and he received a high dose of 5.2 mg/kg Luberta, with asymptomatic neutropenia and We determined that we could reduce the rate of dose delays.”
References
- Sutro Biopharma presents updates on STRO-002, luveltamab tazevibulin (Luvelta), a Phase 1 dose-escalation study and registration plans in advanced ovarian cancer. news release. Strobiopharma. January 9, 2023. Accessed January 11, 2023. https://yhoo.it/3kanoOc
- A study of STRO-002, an anti-folate receptor alpha (FolRα) antibody drug conjugate, in ovarian and endometrial cancer. ClinicalTrials.gov. Updated December 21, 2021. Accessed January 11, 2023. https://clinicaltrials.gov/ct2/show/NCT03748186