Updated interim data regarding safety and anti-tumor activity results in heavily pre-treated patients with ovarian cancer from an on-going Phase I dose-escalation phase clinical study (NCT03748186) evaluating the folate receptor alpha (FRα) antibody drug-conjugate (ADC) STRO-002 (Sutro Biopharma) shows encouraging results.
Folate receptor alpha or FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein is overexpressed in solid tumors, including in 80% of ovarian and endometrial carcinoma. However, the show minimal expression in normal, healthy tissues. FRα, has been demonstrated to contribute to cancer malignancy by acting as a signaling molecule, has become an attractive therapeutic target for cancer therapy using antibody-drug conjugates (ADCs).
STRO-002 is an antibody-drug conjugate or ADC composed of SP8166 (H01), an anti-folate receptor alpha human immunoglobulin G1 antibody, conjugated to a proprietary cleavable drug linker, SC239, containing a tubulin-targeting 3-aminophenyl hemiasterlin payload (SC209). This payload is a natural product derived from marine sponges that, like other structurally diverse peptide-like molecules, binds to the Vinca-peptide site in tubulin, and disrupts normal microtubule dynamics.
The investigational drug was discovered and developed, Sutro’s using proprietary XpressCF+™ cell-free protein synthesis technology. The drug is being developed for the treatment of patients diagnosed with ovarian and/or endometrial cancers. 
A wider therapeutic window
“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 (mg/kg) or higher (of body weight), we saw in the initial post-baseline scans one partial response and 14 patient with stable disease,” Newell added
Difficult to achieve
“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,” Newell explained.
“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,” he concluded.
Interim clinical data
The interim clinical data for STRO-002 in patients treated at dose levels of 2.9 mg/kk or higher included 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 an unconfirmed stable disease at the six-week assessment point.
In the trial, STRO-002 was generally well-tolerated and was mostly associated with mild adverse events (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, M.D., a 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,” Nauman added.
“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 I trial being conducted by our collaborator Bristol Myers Squibb,” noted 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,” Molina said.
Through April 20, 2020, the Phase I 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 the maximum tolerated dose (MTD) has not been reached, Sutro is continuing to actively explore the 5.2 mg/kg o 6.0 mg/kg dose levels as it seeks to determine the recommended Phase II dose.
The ongoing Phase I, open-label, multicenter, dose-escalation trial with dose expansion of STRO-002 was designed to identify the MTD, the recommended Phase II 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.
Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody-drug Conjugate in Ovarian & Endometrial Cancers – NCT03748186
 STRO-002-GM1, a First in Human, Phase 1 Study of STRO-002, an anti-Folate Receptor-alpha (FRα) Antibody Drug Conjugate (ADC), in Patients with Advanced Platinum-Resistant/Refractory Epithelial Ovarian Cancer (OC), including Fallopian Tube or Primary Peritoneal Cancers. Presented during the Virtual Annual Meeting of the American Association for Clinical Research (AACR). Poster: CT125 [Download]
 Li X, Abrahams C, Zhou S, Krimm S, Henningsen R, Stephenson H, Hanson J, Masikat MR, et al. Discovery and activity of STRO-002, a novel ADC targeting folate receptor alpha for ovarian and endometrial cancer. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl): Abstract nr 1782. [Abstract]
 STRO-002 ADC Review | Journal of Antibody-drug Conjugates [Overview]