Based on the positive interim safety data from a phase 1 trial of STRO-002, the phase 2/3 REFRaME study will be initiated to further evaluate the agent in patients with advanced ovarian cancer.
Treatment with STRO-002 (luvelta) in Folate receptor alpha (FolRα)-selected patients with advanced ovarian cancer led to a meaningful clinical benefit, including a 43.8% overall response rate (ORR), median duration of response (DOR) of 5.4 months, and median progression-free survival (PFS) of 6.6 months.1
This interim safety data come from exploratory cohort C of a phase 1 dose-expansion study (NCT03748186). In this cohort,15 patients with advanced ovarian cancer were treated with STRO-002 at the higher dose level of 5.2mg/kg, along with prophylactic pegfilgrastim (Neulasta).
In addition to the efficacy findings, the safety profile of STRO-002 was generally consistent with prior data. Asymptomatic neutropenia was the most common adverse event (AE) and no new safety signals were observed in the trial.
“Today, patients with this form of heavily pre-treated ovarian cancer have extremely limited treatment options available to them, and unfortunately, experience poor outcomes,” said R. Wendel Naumann, MD, professor and director of Gynecologic Oncology Research and associate medical director of clinical trials at the Levine Cancer Institute, Atrium Health, and a co-lead principal investigator in the STRO-002-GM1 studies, in the press release. “To date, luvelta continues to demonstrate encouraging efficacy data, which was further supported by results from the dose-expansion cohort. The safety profile was shown to be manageable and notably devoid of ocular complications across a broad spectrum of patients with FolRα-selected ovarian cancer.”
STRO-002 is a novel FolRα-targeting antibody drug conjugate (ADC). In this study of STRO-002, cohort C was initiated to evaluate the use of prophylactic pegfilgrastim for patients treated with the higher dose of the agent.2
Compared with patients who were not given prophylactic pegfilgrastim in the dose-expansion cohort at the higher dose of 5.2mg/kg, early data from the initial 10 patients in cohort C showed substantial reductions in grade 3 or greater neutropenia and in instances of dose delays
Findings from the trial also demonstrated that treatment with STRO-002 at this higher dose led to a substantial clinical benefit in FolRα-selected patients, defined by Tumor Proportion Score (TPS) of >25%. Regardless of the starting dose, the ORR was 37.5% (n = 32), median DOR was 5.5 months (n = 12), and median PFS was 6.1 months (n = 35).For patients who were unselected for FolRα, treatment with STRO-002 demonstrated a FolRα-dependent response with an 11.1% ORR (n = 9), median DOR of 2.9 months (n = 1), and median PFS of 3.8 months (n = 9).
However, the higher starting dose of 5.2 mg/kg led to greater patient benefit vs the lower dose of 4.3mg/kg. With the higher starting dose, the ORR was 43.8% (n = 16), median DOR was 5.4 months (n = 7), and median PFS was 6.6 months (n = 16) vs an ORR of 31.3% (n = 16), median DOR of 13 months (n = 5), and median PFS of 6.1 months (n = 19) for FolRα-selected patients given the lower dose of 4.3 mg/kg.
Regarding safety, data were consistent with prior findings. The primary AE from the dose-expansion cohort was predominantly asymptomatic neutropenia. No meaningful ocular toxicity signals or complications reported.
Grade 3 or greater neutropenia decreased from 66.7% to 10.0% with the higher dose, resulting in an 85.0% decrease in grade 3 or higher neutropenia rates at the first cycle of the agent (P = .006). Further, instances of dose delays at the second cycle of STRO-002 were reduced by 60.6% (P = .021).
In addition to this promising data, the company plans to initiate the registration-directed phase 2/3 study, REFRaME, in 2023. This phase of the trial will evaluate 25 patients at the 5.2 mg/kg dose with pegfilgrastim delivered prophylactically for 2 cycles. Then, patients will be given a step-down dose to 4.3 mg/kg. From the start of the trial, the other 25 patients will be evaluated at the 4.3 mg/kg dose without prophylactic pegfilgrastim.
At the end of the phase 3 portion of the trial, the company hopes that full approval of the agent can be sought based on PFS as the primary end point which will compare the STRO-002 arm (n = 160) with the standard of care arm (n = 160).
“We are pleased with our phase 1 dose-expansion efficacy data, which are generally consistent with previously reported results and demonstrate luvelta’s potential in a difficult-to-treat patient population. Through the addition of cohort C, we were able to evaluate patients at the higher dose of STRO-002 at 5.2mg/kg with the use of prophylactic pegfilgrastim and determined that the rates of asymptomatic neutropenia and dose delays could be diminished,” said Bill Newell, chief executive officer of Sutro Biopharma, in the press release. “Our meeting with the FDA in 2022 provided a framework for our path forward on the registration-directed phase 2/3 trial for platinum resistant ovarian cancer patients, called REFRaME, which we plan to initiate in the second quarter of 2023.”