Monday, April 27, 2020
Sutro Biopharma, Inc., a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, today announced updated interim data regarding safety and anti-tumor activity results in heavily pre-treated patients with ovarian cancer from its on-going Phase 1 clinical trial (dose escalation phase) evaluating its folate receptor alpha (FolRα) antibody drug-conjugate (ADC) STRO-002.
"We designed STRO-002 to have a wider therapeutic window, with the potential for improved tumor control and better patient tolerability, than other FolRα targeted therapies," said Bill Newell, CEO of Sutro Biopharma. "The data we present today from this all-comers trial suggest that our optimally designed ADC can achieve these objectives. In 75% (15 of 20) of ovarian cancer patients at STRO-002 dose levels of 2.9 milligrams per kilogram (mpk) or higher, we saw in the initial post-baseline scans one partial response and 14 stable disease. This level of tumor control is typically very difficult to achieve in these patients who have been heavily pre-treated, with a median of five prior lines of other therapies, and who have such advanced disease. Equally encouraging are the data showing that 13 patients had a ≥50% reduction or normalization of CA-125, including six confirmed responses, six unconfirmed responses and one prolonged CA-125 normalization. Of these 13 patients, one patient is not yet evaluable under RECIST criteria. All of the other 12 patients (100%) have also achieved stable disease (confirmed or unconfirmed) or a confirmed partial response. With 89% of adverse events (AEs) reported to be grade 1 or 2, we believe the emerging safety profile reflects our optimized design approach."
The interim clinical data for STRO-002 in patients treated at dose levels of 2.9 mpk or higher include: one patient with an ongoing confirmed partial response (36 weeks); five patients with confirmed stable disease (three up to 18 weeks, two up to 27 weeks); and seven ongoing patients who have unconfirmed stable disease at the six-week assessment point.
STRO-002 was generally well-tolerated and was mostly associated with mild AEs. Eighty-nine percent (89%) of AEs were grade 1 or grade 2 and prophylactic corticosteroid eye drops have not been necessary. Grade 3 treatment emergent AEs included fatigue, neutropenia, arthralgia, diarrhea, peripheral neuropathy and myalgia, with the only grade 4 treatment emergent AE being neutropenia; all neutropenias were reversible within one week.
"The preliminary evidence of anti-tumor activity we observed is encouraging, particularly in this heavily pre-treated patient population," said Wendel Naumann, MD, gynecologic oncologist at Levine Cancer Institute and a principal investigator on the STRO-002 study. "With limited therapeutic options for these patients, we are excited to continue to advance this clinical program to further investigate its therapeutic potential."
"These data support Sutro's continued development of targeted therapies for cancer patients and joins two other Sutro-developed and manufactured ADCs in clinical trials, including our BCMA-targeted ADC which is in a Phase 1 trial being conducted by our collaborator Bristol Myers Squibb," said Arturo Molina, MD, Sutro's Chief Medical Officer. "It is extremely encouraging that we see this preliminary evidence of anti-tumor activity at this stage of development. As we advance STRO-002 in the clinic, we plan to share additional data on the efficacy and safety of STRO-002 by the end of 2020 and we look forward to the potential to bring a new treatment option to ovarian cancer patients."
Through April 20, 2020, the Phase 1 trial of STRO-002 has enrolled 30 patients with recurrent platinum resistant or refractory ovarian cancer, without regard to FolRα expression levels. A dose expansion phase of this trial is planned to commence in the second half of 2020. Although maximum tolerated dose (MTD) has not been reached, Sutro is continuing to actively explore the 5.2 mpk to 6.0 mpk dose levels as it seeks to determine the recommended Phase 2 dose.
The ongoing Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is designed to identify the MTD, the recommended Phase 2 clinical dose and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. This trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+™ cell-free protein synthesis technology.