Sutro Biopharma, Inc. announced results from a Phase 1 dose-expansion study of STRO-002 (luvelta), a novel Folate receptor alpha (FolRa)-targeting ADC and interim safety data from exploratory cohort C, a cohort of 15 patients with advanced ovarian cancer treated at the higher dose of luvelta, (5.2mg/kg), along with prophylactic pegfilgrastim. Additionally, the company provided details on the design of the registration-directed Phase 2/3 study, REFRaME, to start in the second quarter of 2023. Results demonstrated that luvelta provided substantial clinical benefit in FolRa-selected patients, defined by Tumor Proportion Score (TPS) of >25%, with a 37.5% overall response rate (ORR), median duration of response (median DOR) of 5.5 months, and median progression free survival (median PFS) of 6.1 months, regardless of starting dose.

Results also demonstrated the higher starting dose of 5.2 mg/kg providing greater patient benefit compared to the lower dose of 4.3mg/kg. FolRa-selected patients account for approximately 80% of the patient population in advanced ovarian cancer, as represented in the patient stratification in the Phase 1 study. Consistent with prior luvelta data, the primary adverse event from the dose-expansion cohort was predominantly asymptomatic neutropenia, with no meaningful ocular toxicity signals or complications reported.

In cohort C, an additional 15 patients with advanced ovarian cancer were enrolled and treated with prophylactic pegfilgrastim on Day 8 after each 5.2 mg/kg administration of luvelta. Initial data on neutropenia and dose delays were available on the first 10 patients, which showed that patients in cohort C experienced substantial decreases in neutropenia and potential increases in dose intensity, due to decreased dose delays. Summary of Results from Phase 1 Dose-Expansion Study: Based on the results, luvelta has demonstrated the potential to provide meaningful clinical benefit to a substantially broader patient population than the on-label patient population of the approved FolRa-targeting agent: Patients who were FolRa-selected, defined by TPS>25%, regardless of starting dose, demonstrated an ORR of 37.5% (n=32) with a median DOR of 5.5 months (n=12) and a median PFS of 6.1 months (n=35); Targeted luvelta patient population is approximately 80% of advanced ovarian cancer patients based on pooled Phase 1 biomarker data; Luvelta demonstrated a FolRa-dependent response, with patients who were unselected for FolRa (TPS=25%) demonstrating an 11.1% ORR (n=9) with a median DOR of 2.9 months (n=1) and a median PFS of 3.8 months (n=9).

Luvelta, when given to patients at a starting dose of 5.2 mg/kg, provided greater patient benefit than a starting dose of 4.3 mg/kg: FolRa-selected patients given the higher dose of luvelta (5.2 mg/kg) demonstrated higher response rates: ORR of 43.8% (n=16); Median DOR of 5.4 months (n=7); Median PFS of 6.6 months (n=16); FolRa-selected patients given the lower dose of luvelta (4.3 mg/kg) demonstrated: ORR of 31.3% (n=16); Median DOR of 13 months (n=5); Median PFS of 6.1 months (n=19). Consistent with earlier reported data, the primary adverse event from the dose-expansion cohort was asymptomatic, transient neutropenia; Cohort C was initiated to explore the use of prophylactic pegfilgrastim for patients treated with the higher dose of luvelta (5.2mg/kg). Early results in the initial 10 patients in cohort C, when compared to patients who were not given prophylactic pegfilgrastim in the dose-expansion cohort at the higher dose (5.2mg/kg), showed substantial reductions in Grade 3+ neutropenia and in instances of dose delays: Grade 3+ neutropenia was reduced from 66.7% to 10.0%, resulting in an 85.0% decrease in Grade 3+ neutropenia rates at the first cycle of luvelta (p=0.006); Instances of dose delays at the second cycle of luvelta were reduced by 60.6% (p=0.021).

Planned Phase 2/3 Study Details: As discussed with the U.S. Food and Drug Administration (FDA), the Phase 2/3 REFRaME study is planned to begin with a randomized, run-in dose confirmation phase. In this phase of the trial, 25 patients will be evaluated at the 5.2 mg/kg dose with pegfilgrastim delivered prophylactically for two cycles followed by a step-down dose to 4.3 mg/kg. The other 25 patients will be evaluated from the start at the 4.3 mg/kg dose without prophylactic pegfilgrastim.

Following this 50-patient phase of the study, additional patients will be randomized between these two luvelta dose levels, and standard of care (chemotherapy). Upon agreement with FDA on the go-forward dose versus standard of care, the dose level of luvelta not chosen will be dropped. Upon having data on approximately 110 patients in the selected dose of luvelta arm, Sutro will look to apply for accelerated approval based on ORR as the primary endpoint.

At the end of the Phase 3 portion of the trial, full approval can be sought based on PFS as the primary endpoint comparing the luvelta arm (n=160) and the standard of care arm (n=160).