Initial safety data of STRO-002 shows potent anti-tumor activity in preclinical endometrial cancer patient-derived xenograft (PDX) models were presented at the AACR-NCI-EORTC.
FRα is overexpressed in 80% of ovarian and endometrial carcinoma and shows minimal expression in normal tissues.
STRO-002 is a folate receptor alpha (FolRα-) targeting antibody-drug conjugate (ADC) being developed by San Francisco-based Sutro Biopharma. The agent is currently being investigated in a Phase I clinical trial of patients with ovarian and endometrial cancers. This investigational drug is the second product candidate to be evaluated in clinical trials.
XpressCF+™ technology platform
The investigational agent was generated with Sutro’s cell-free antibody production system (XpressCF™) and site-specific conjugation (XpressCF+™) platform, which uses the non-natural amino acid pAMF. STRO-002 has a drug-antibody ratio (DAR) of 4 and contains the proprietary tubulin-targeting 3-aminophenyl hemiasterlin warhead SC209, a potent cytotoxin that is rapidly cleared and a weak substrate for efflux pumps
To date, 13 patients have been treated in the Phase I study of STRO-002. According to the study data, the maximum tolerated dose (MTD) has not been reached. Dose escalation continues with two patients currently being treated at the 6 mg/kg dose level and having completed the dose limiting toxicity (DLT) observation period. There have been no DLTs and no infusion reactions to date in these heavily pre-treated patients.
Preliminary evidence of anti-tumor activity was observed in a patient who achieved a confirmed partial response by RECIST 1.1 criteria. This patient also achieved and confirmed a CA-125 response for at least 28 days.
Stable disease by RECIST 1.1 has been confirmed in two ongoing patients at cycles 5 and 10 of study treatment. Three ongoing patients at the 4.3 mg/kg dose level have unconfirmed stable disease per RECIST 1.1 at cycle 3. Patients are not receiving prophylactic corticosteroid eye drops.
Ninety-five percent (95%) of adverse events were grade 1 or grade 2. The preliminary pharmacokinetic (PK) profile reveals an estimated half-life for the total antibody of 22-76 hours with increasing exposure in an apparent dose dependent manner.
Anti-tumor activity of STRO-002 was assessed in preclinical PDX models of endometrial cancer that expressed varying levels of FolRα. High FolRα-expressing models showed the highest tumor growth inhibition. Some models with low and medium FolRα expression also exhibited good tumor growth inhibition.
“The emerging safety profile of STRO-002 is very promising,” said Arturo Molina, M.D., Chief Medical Officer at Sutro Biopharma.
“Antibody-drug conjugates offer the ability to preferentially kill tumor cells while avoiding healthy cells. Early signs of clinical benefit are encouraging, and we believe STRO-002 has potential in this heavily pre-treated population of patients with advanced, relapsed and refractory ovarian cancer,” Molina added.
“STRO-002 is our second proprietary ADC in clinical trials, and one of our four ADC clinical product candidates from our platform in the past three years, including those of our collaborators,” Bill Newell, Sutro’s Chief Executive Officer said.
“Our goal is to continue to develop targeted therapies for cancer patients. The STRO-002 data add to the growing body of evidence that our ADC development platform and pipeline of products has the potential to help patients with life-threatening cancers,” Newell noted.
The ongoing Phase I, open-label, multicenter, dose escalation study with dose expansion of STRO-002 is designed to identify the MTD, the recommended Phase II 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.
Uyar D, Schilder R, Naumann RW, Braiteh F, Hamilton E, Diab S, Moroney J, Penson R, et al. Antitumor activity of STRO-002, a novel anti-folate receptor-α (FRα) antibody drug conjugate (ADC), in patient-derived xenograft (PDX) models and preliminary Phase I dose escalation safety outcomes in patients with ovarian carcinoma (OC).C095 | Poster Session C: Tubulin-interacting Agents | Level 2 – Hall D |Tuesday, Oct 29 | 12:30pm – 4:00pm. | AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference, held October 26 – 30, 2019 in the Hynes Convention Center Boston, MA.