Antibody-Drug Conjugate STRO-002 Active in Advanced Ovarian Cancer

R. Wendel Naumann, MD

The anti­—folate receptor alpha (FRα) antibody-drug conjugate (ADC) STRO-002 showed early clinical promise in an all-comer population of patients with advanced platinum-resistant/refractory ovarian cancer, according to findings from the small phase I STRO-002-GM1 trial presented during the 2020 AACR Virtual Annual Meeting.

One patient had an ongoing confirmed partial response and remained on study at >36 weeks. An additional 6 patients had confirmed stable disease (SD), including 3 patients at up to 18 weeks, 2 patients at up to 27 weeks, and 1 patient at up to 39 weeks who remained on study for 45 weeks. Four other patients had unconfirmed SD at a 6-week assessment.

“STRO-002 is the first ADC generated with cell free protein synthesis technology to be tested in patients with solid tumors. The preliminary safety profile and evidence of antitumor activity and clinical benefit is encouraging, particularly in this heavily pretreated, platinum-resistant/refractory patient population that has not been enriched for FRα expression,” said lead investigator R. Wendel Naumann, MD, a gynecologic oncologist at Levine Cancer Institute, Carolinas HealthCare System/Atrium Health.

The open-label, dose-escalation/expansion phase 1 STRO-002-GM1 trial was launched in March 2019 and is being conducted at 10 clinical sites throughout the United States. At the time of the data presentation, the trial had enrolled 27 patients with recurrent platinum-resistant or refractory ovarian cancer, or patients who have been treated with at least 2 prior platinum regimens. An all-comer population was enrolled, regardless of their level of FRα expression. There was also no limit on the number of prior chemotherapy regimens received.

Among all 27 patients, the median age was 60 years (range, 47-76). The median time from diagnosis was 3.9 years (range, 0.6-17.1) and the median number of prior lines of therapy was 5 (range, 2-10). Sixteen patients had received a PARP inhibitor, 20 had prior bevacizumab (Avastin), 7 had prior checkpoint therapy, and 8 had received other experimental therapies. Overall, 12 patients had received more than 2 prior platinum-based regimens.

Patients on the trial received STRO-002 intravenously on day 1 of each 21-day cycle until disease progression. Five patients received dose levels of ≤1.8 mg/kg. The remaining 22 patients received STRO-002 at doses of ≥2.9 mg/kg, with the maximum dose being 6.4 mg/kg. The median number of doses was 3 (range, 1-15). The primary outcome measures are safety, maximum-tolerated dose, recommended phase 2 dose, pharmacokinetics, and preliminary efficacy.

Among the patients who received a dose of ≥2.9 mg/kg, “All but 3 of the patients had a decrease in the CA-125 from baseline. Forty-one percent of the patients had either a normalization of the CA-125 or a Gynecological Cancer Intergroup (GCIG)—defined response. Of the 8 patients with a CA-125 response, half were confirmed,” said Naumann.

Overall, 15 (56%) of the 27 patients remain on study treatment, including all patients with a GCIG-defined CA-125 response or CA-125 normalization. Of the 27 patients, 6 patients were not yet evaluable for efficacy.

“STRO-002 was generally well tolerated and mostly associated with mild events,” said Naumann.

The safety population included 26 patients. Overall, 89% of all adverse events (AEs) reported were grade 1 or 2. Grade 3 AEs included neutropenia (23%), arthralgia (15%), abdominal pain (12%), fatigue (8%), diarrhea (4%), and peripheral neuropathy (4%). The only grade 4 toxicity reported was neutropenia (n = 6), which Naumann said resolved within 1 week.

Two dose-limiting toxicities occurred: neuropathy at the 6.0 mg/kg dose level and bone pain at the 6.4 mg/kg dose level. The maximum-tolerated dose and recommended phase 2 dose have not yet been determined. However, Naumann noted that, “Rates of arthralgia, exacerbation of peripheral neuropathy, and reversible neutropenia suggest that the recommended phase 2 dose will be in the 5.2 to 6.0 mg/kg range.”

Enrollment is ongoing in the dose-escalation phase of the trial, which will include 40 patients with FRα-expressing relapsed/refractory ovarian cancer.

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.