STRO-002 Shows Early Efficacy, Safety in Heavily Pretreated Epithelial Ovarian Cancer

The novel anti-folate receptor alpha (FolRα) antibody-drug conjugate (ADC) STRO-002 demonstrated encouraging efficacy with a tolerable safety profile in patients with advanced platinum-resistant or refractory epithelial ovarian cancer, according to updated interim results from the phase 1 STRO-002-GM1 trial (NCT03748186).¹

Results showed that the ADC elicited an overall response rate (ORR) of 24% in a total of 33 evaluable patients who had post-baseline scans available. Durability of response was demonstrated in 44% of patients who received treatment for 16 weeks or more and 12% of those who received treatment for 1 year or longer. The disease control rate (DCR) with STRO-002 was 47% (n = 14/30).

“We are pleased to observe improved efficacy outcomes as our data mature with longer follow-up, and the observed rate of objective response, stable disease, and overall disease control during this study suggest that STRO-002 is potentially superior to other targeted ADC therapies being studied currently in ovarian cancer,” Arturo Molina, MD, MS, chief medical officer of Sutro Biopharma, stated in a press release.

STRO-002 is the first ADC to be produced with cell-free protein synthesis technology for testing in patients with solid tumors. STRO-002 contains an anti-FolRα human IgG1 antibody, SP8166, which is conjugated to a cleavable DBCO-3-aminophenyl-hemiasterlin drug-linker through site-directed conjugation technology to develop an ADC with the predominant species that has a drug-antibody ratio of 4.²

The open-label, dose-escalation/expansion phase 1 trial was launched in March 2019 and is being conducted across 10 clinical sites throughout the United States. Patients with recurrent platinum-resistant or -refractory ovarian cancer and those who received treatment with at least 2 previous platinum regimens have been enrolled. Notably, an all-comer population was enrolled to the trial, irrespective of their level of FRα expression. There was no limit to the number or previous lines of chemotherapy regimens a patient had received.³

The primary end point of the dose-expansion portion of the STRO-002-GM1 trial is ORR to determine the antitumor activity of the ADC. A secondary objective in the dose-escalation phase was to characterize the pharmacokinetics (PK) and immunogenicity of the drug. Key secondary objectives in the dose-expansion phase include duration of response, progression-free survival, as well as additional safety and PK. The exploratory objectives in the dose-escalation phase include preliminary efficacy, pharmacokinetic correlation with efficacy, and biomarkers; objectives in the dose-expansion phase include further PK correlation with efficacy and biomarkers.

To date, a total of 39 patients have been enrolled on the trial; 77% (n =30) have endothelial ovarian cancer, 18% (n = 7) have fallopian tube, and 5% (n = 2) have primary peritoneal. The median age of participants is 61 years. Moreover, the majority of participants, or 59% (n = 23), have an ECOG performance status of 0, while 41% (n = 16) have a status of 1.

The median time from diagnosis to treatment was 3.9 years and the median prior lines of treatment was 5. All patients had previously received treatment with platinum-based chemotherapy and 36% had received 3 more previous platinum-containing regimens. Additionally, 97% (n = 38) of patients received prior taxane treatment, 79% (n = 31) received bevacizumab (Avastin), 59% (n = 23) had PARP inhibitors, 21% (n = 8) had checkpoint inhibitors, and 34% (n = 13) had received experimental therapy.

Additional results showed that in the 30 patients evaluable for RECIST response, 8 patients achieved partial responses (PRs) with STRO-002; 2 were confirmed and 6 were unconfirmed. Moreover, 7 patients with PRs and 13 patients who achieved stable disease experienced a DCR of 60% at 12 weeks or greater.

Twenty-nine percent of patients who received STRO-002 at a dose of 2.9 mg/kg or higher continued on the study for longer than 24 weeks. Forty-one percent of patients remained on study for over 16 weeks, 15% for longer than 45 weeks, and 6% for over 1 year. Forty-seven percent of patients remain on treatment with the ADC.

Additionally, in those who received a dose of 2.9 mg/kg or higher and were evaluable for CA-125 response (n = 24), 67% (n = 16/24) experienced a 50% or greater reduction in CA-125 and 42% (n = 10/24) had confirmed CA-125 response per Gynecologic Cancer Intergroup criteria. Eight percent (n = 2/24) have an ongoing response with confirmation pending or possible, while 21% (n = 5/24) have discontinued without confirmation.

With regard to safety, those who received STRO-002 were found to have mostly mild adverse effects; 88% of toxicities reported were either grade 1 or 2 in severity. Of the 39 patients, 67% (n = 26) experienced fatigue, 59% (n = 23) reported nausea, 51% (n = 20) experienced neutropenia/neutrophil count decrease, 44% (n = 17) had arthralgia, 44% (n = 17) had decreased appetite, 31% (n = 12) experienced abdominal pain, 31% (n = 12) had increased aspartate aminotransferase, 29% (n = 11) had diarrhea, 26% (n = 10) reported peripheral neuropathy, and 26% (n = 10) experienced vomiting.

Two dose-limiting toxicities were reported: 1 patient who received the agent at 6.0 mg/kg experienced neuropathy and 1 patient who was given the agent at a dose of 6.4 mg/kg reported bone pain. Only 1 case of grade 3 febrile neutropenia was reported. One grade 5 event of death on day 12 of cycle 1 was reported, although no cause was reported, and it was not determined to be related to study treatment per investigator assessment.

Notably, a low rate of keratitis was observed with long-term dosing of the ADC. Only 1 patient required therapeutic corticosteroid eyedrops.

“Taken together with the optimized design approach to ADC safety, we believe that STRO-002 will be a potent and well-tolerated treatment option for patients,” added Molina. “Next up, we plan to initiate a dose-expansion trial in patients with less heavily pretreated ovarian cancer in the fourth quarter of 2020.”

References

1. Sutro Biopharma presents promising STRO-002 interim phase 1 clinical data in ovarian cancer at the 2020 IGCS Annual Global Meeting. News release. Sutro Biopharma. September 9, 2020. Accessed September 11, 2020. https://bit.ly/3kdC9dx.
2. Naumann RW, Braiteh FS, Diaz JP, et al. Phase 1 dose-escalation study of STRO-002, an anti-folate receptor alpha (FRα) antibody-drug conjugate (ADC), in patients with advanced platinum-resistant/refractory epithelial ovarian cancer. Presented at: 2020 International Gynecologic Cancer Society Virtual Healthcare Conference; September 10-13, 2020; Virtual. https://bit.ly/3iAhP65.
3. Naumann RW, Uyar D, Moroney JW, et al. 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 at: 2020 AACR Virtual Annual Meeting I; April 27-28, 2020. Abstract CT125.