FDA Fast Track Designation Granted to Navicixizumab for Heavily Pretreated Ovarian Cancer

The FDA has granted a fast track designation to navicixizumab (OMP-305B83) for the treatment of patients with high-grade ovarian, primary peritoneal, or fallopian tube cancer who have received ≥3 prior therapies and/or prior bevacizumab (Avastin).¹

The agent has been investigated in a phase Ia clinical trial of patients with refractory solid tumors and is now being studied in combination with paclitaxel in a phase Ib trial of patients with advanced heavily pretreated ovarian cancer (NCT03030287).

“We are pleased that the FDA continues to recognize the potential of navicixizumab to become a viable new treatment option for patients with platinum-resistant ovarian cancer who failed multiple other therapies,” Jill Henrich, senior vice president of regulatory affairs at Mereo BioPharma, the company developing navicixizumab, said in a press release. “This designation follows our successful Type B End of Phase I meeting with the FDA held in July 2019 regarding a potential pathway for accelerated approval for navicixizumab where the FDA agreed in principle on an outline for a phase II clinical trial that could potentially support accelerated approval of navicixizumab in patients with ovarian cancer who have become resistant to prior therapies.”

Navicixizumab is an anti-DLL4/VEGF bispecific antibody that has demonstrated robust in vivo antitumor efficacy in a number of solid tumor xenografts.

In the phase Ia trial of the monotherapy, 66 patients with various solid tumors were treated once every 3 weeks in 1 of 8 dose-escalation cohorts or an expansion cohort.²

The median age of all patients was 60 and 68% of patients were female. The most common tumor types included in the trial were ovarian cancer (n = 12) and colorectal cancer (n = 11).

Partial responses were seen in 4 patients, 3 of which had ovarian cancer, and an additional 17 patients had stable disease. Overall, 19 patients achieved a reduction in the size of their target lesion. Four patients remained on treatment for more than 300 days, and 2 remained on for more than 500 days.

Only 1 dose-limiting toxicity was observed so a maximum tolerated dose was not reached. The investigators chose 7.5 mg/kg for the dose used in the expansion cohort.

The most common treatment-related adverse events observed were hypertension (57.6%), headache (28.8%), fatigue (25.8%), and pulmonary hypertension (18.2%). Pulmonary hypertension was considered to be more severe at higher doses.

The ongoing dose-escalation/expansion phase Ib trial is exploring the safety, efficacy, and pharmacokinetics of navicixizumab in combination with paclitaxel in patients with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer. The trial consists of a screening period, a treatment period, and a post-treatment follow-up period of approximately 12 months. About 30 patients were expected to be enrolled across 5 study centers in the United States.

The incidence of dose-limiting toxicities is the primary endpoint of the trial and secondary endpoint include response rate by both RECIST and CA-125 criteria, progression-free survival, safety, and immunogenicity.

According to interim results of the phase Ib trial presented at the 2018 ESMO Congress, 18 patients had been treated with 5 patients still on treatment.³All of the patients had received prior paclitaxel and 13 had received prior bevacizumab. The median number of prior therapies was 4 (range, 2-8).

Partial responses were seen in 8 patients (44%) and 6 others (33%) had stable disease, for a clinical benefit rate of 78%.

Common treatment-related adverse events included hypertension (67%), fatigue (44%), diarrhea (44%), headache (22%), neutropenia (17%), GERD (17%), and decrease appetite (17%). Other significant adverse events included infusion reaction (6%), grade 2 pulmonary hypertension (6%), grade 4 thrombocytopenia (6%), and grade 4 gastrointestinal perforation (6%).

References

1. Mereo BioPharma Receives FDA Fast Track Designation for Navicixizumab for the Treatment of Heavily Pretreated Ovarian Cancer [press release]. London and Redwood City, CA: Mereo BioPharma Group plc; October 7, 2019. https://bit.ly/31V3l8o. Accessed October 7, 2019.
2. Jimeno A, Moore KN, Gordon M, et al. A first-in-human phase 1a study of the bispecific anti-DLL4/anti-VEGF antibody navicixizumab (OMP-305B83) in patients with previously treated solid tumors.Invest New Drugs. 2019;37(3):461-472. doi: 10.1007/s10637-018-0665-y.
3. Fu S, Corr B, Hamilton E, et al. A Phase 1b Study of Navicixizumab & Weekly Paclitaxel in Heavily Pre-Treated Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer.Ann Oncol. 2018;29(suppl 8):viii332-viii358. doi: 10.1093/annonc/mdy285.