On January 9, 2023 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its results from a Phase 1 dose-expansion study of STRO-002 (luvelta), a novel Folate receptor alpha (FolRα)-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 (Press release, Sutro Biopharma, JAN 9, 2023, View Source [SID1234626112]).

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Results demonstrated that luvelta provided substantial clinical benefit in FolRα-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. FolRα-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.

"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 Dr. R. Wendel Naumann, Professor and Director of Gynecologic Oncology Research and Associate Medical Director of Clinical Trials at the Levine Cancer Institute, Atrium Health in Charlotte, North Carolina, and a co-lead principal investigator in the STRO-002-GM1 studies. "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."

Commented Bill Newell, Chief Executive Officer of Sutro: "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 luvelta at 5.2mg/kg with the use of prophylactic pegfilgrastim and determined that the rates of asymptomatic neutropenia and dose delays could be diminished. 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."

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 FolRα-targeting agent

Patients who were FolRα-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 FolRα-dependent response, with patients who were unselected for FolRα (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

FolRα-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)

FolRα-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).

Webcast Details

The data will be presented by members of the Sutro management team and Dr. R. Wendel Naumann, a co-lead principal investigator in the STRO-002-GM1 studies. Dr. Naumann is a Professor and Director of Gynecologic Oncology Research and Associate Medical Director of Clinical Trials at the Levine Cancer Institute, Atrium Health in Charlotte, North Carolina. Dr. Naumann is also a member of Sutro’s Clinical Advisory Board.

Monday, January 9, 2023 at 1:30 pm PT, or 4:30 pm ET

To access and register for the live audio webcast, please go to View Source

The webcast information will also be available through the News & Events section of the Investors portion of the Company’s website at www.sutrobio.com. An archived replay will be available for at least 30 days after the event.