FDA Grants Fast Track Designation to STRO-002 for Advanced Ovarian Cancer

The FDA has granted a fast track designation to STRO-002 as a potential therapeutic option for patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received 1 to 3 lines of systemic therapy.¹

The folate receptor α (FolRα)–targeting antibody-drug conjugate (ADC) is under examination in the phase 1 STRO-002-GM1 trial (NCT03748186), where it has showcased encouraging efficacy and tolerability in this patient population.

The most recently released data from the trial showed that 10 of 31 evaluable patients met RECIST criteria for response to treatment; of these patients, 1 experienced a complete response and 9 achieved a partial response (PR). Three of the PRs are confirmed and 6 are unconfirmed.²

Moreover, the disease control rate was 74% (n = 23) at 12 weeks, and at 16 weeks, this rate was 58% (n = 18). Thirteen percent (n = 4) of patients were on treatment for 52 weeks, with 3 patients continuing treatment for longer than 64 weeks.

“We are pleased with the FDA’s decision to grant fast track designation for STRO-002 and welcome the opportunity to have more frequent interactions with the agency,” Arturo Molina, MD, MS, chief medical officer of Sutro Biopharma, stated in a press release. “We continue to be enthused by the potential of the STRO-002 program, which has shown encouraging preliminary activity and tolerability in our phase 1 dose-escalation study in ovarian cancer, and plan to continue to work with the FDA to potentially accelerate our clinical and regulatory efforts.”

STRO-002 is the first ADC to be developed with cell-free protein synthesis technology for investigating in patients with solid tumors. The agent is comprised of the 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 agent with the predominant species that has a drug-antibody ratio of 4.³

The open-label, dose-escalation/expansion phase 1 trial was launched in March 2019 and is being done at 10 clinical sites in the United States. To be eligible to enroll, patients needed to have recurrent platinum-resistant or -refractory ovarian cancer and have previously received at least 2 platinum regimens. Notably, patients were enrolled irrespective of their level of FRα expression, and no limit was set regarding the number of prior lines of chemotherapy received.⁴

For the dose-expansion portion of STRO-002-GM1, the primary end point is objective response rate, and a secondary objective in the dose-escalation phase is to describe the pharmacokinetics (PK) and immunogenicity of the ADC. In the dose-expansion phase of the research, other secondary objectives include duration of response, progression-free survival, safety, and additional information regarding PK. Key exploratory objectives in the dose-escalation phase include preliminary efficacy of the agent, PK association with efficacy, and biomarkers. In the dose-expansion phase, investigators will continue to evaluate the PK correlation with efficacy and biomarkers.

The dose-escalation cohort has been completed and the dose-expansion cohort has enrolled participants from clinical sites throughout the United States and Spain. Enrollment to this phase is ongoing. In the dose-expansion phase, study participants were randomized 1:1 to receive STRO-002 at a dose of 4.3 mg/kg or 5.2 mg/kg every 3 weeks.

A total of 39 patients had been enrolled to the study as of September 9, 2020.3 Of these patients, 77% (n = 30) have endothelial cancer, 18% had fallopian tube disease, and 5% had primary peritoneal disease. The median age of participants was 61 years, 59% had an ECOG performance status of 0, and 41% had a status of 1.

Moreover, the median time from diagnosis to treatment was 3.9 years, and patients had previously received a median of 5 lines of therapy. All had received prior platinum-based chemotherapy, with 36% having received 3 or more prior platinum-containing regimens. Ninety-seven percent previously received a taxane, 79% received bevacizumab (Avastin), 59% received PARP inhibitors, 21% received checkpoint inhibitors, and 34% received an investigational treatment.

At the time of the 2020 International Gynecologic Cancer Society Virtual Healthcare Conference, 67% (n = 16) of 24 patients who had received the agent at a dose of 2.9 mg/kg or higher and were evaluable for CA-125 response reported a 50% or greater reduction in CA-125. Moreover, 42% of patients had confirmed CA-125 response per Gynecologic Cancer Intergroup criteria. Eight percent of patients were experiencing an ongoing response with confirmation pending or possible and 21% had discontinued without confirmation.

The majority of adverse effects (AEs) reported with the ADC were mild, with 88% of toxicities either grade 1 or 2. Sixty-seven percent of the 39 patients reported fatigue, and 59% reported nausea, 51% had neutropenia/neutrophil count decrease, 44% had arthralgia, and 44% experienced decreased appetite. Other AEs experienced with the agent included abdominal pain (31%), increased aspartate aminotransferase (31%), diarrhea (29%), peripheral neuropathy (26%), and vomiting (26%).

Of the 2 dose-limiting toxicities reported, 1 patient had received a 6.0-mg/kg dose of the agent and reported neuropathy and the other patient received a 6.4-mg/kg dose and experienced bone pain. One case of grade 3 febrile neutropenia was observed. On day 12 of cycle 1, one grade 5 event of death was reported, but no cause was determined; the effect was not determined by investigator assessment to be associated with study treatment.

“Receiving fast track designation is an important recognition for STRO-002 as a potentially best-in-class FolRα ADC for women with ovarian cancer,” Bill Newell, chief executive officer of Sutro Biopharma, stated in a press release. “We look forward to further collaboration with the FDA to bring this potentially important therapeutic option to women in advanced stages of their disease with limited treatment options.”

References

1. Sutro Biopharma announces STRO-002 FDA fast track designation for patients with advanced ovarian cancer. News release. Sutro Biopharma, Inc. August 18, 2021. Accessed August 18, 2021. https://prn.to/2UuhmLR
2. Sutro Biopharma announces encouraging interim data on STRO-002 phase 1 dose-escalation study for patients with ovarian cancer. News release. Sutro Biopharma, Inc. December 3, 2020. Accessed August 18, 2021. https://prn.to/3gdpzvD
3. 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.
4. 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.