1389 - A Phase 1b Study of Navicixizumab & Weekly Paclitaxel in Heavily Pre-Treated Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer.

Background

Anti-VEGF & anti-DLL4 have both demonstrated single agent activity in ovarian cancer. Navicixizumab is an anti-DLL4/VEGF IgG2 bispecific monoclonal antibody that had a response rate of 25% (3/12) in heavily pretreated ovarian cancer pts who were treated in an earlier single agent phase Ia trial.

Methods

This is an ongoing Phase 1b study of paclitaxel & navicixizumab in platinum resistant ovarian cancer pts who have failed > 2 prior therapies &/or bevacizumab. Paclitaxel 80 mg/m2 is given on Days 1, 8 and 15 & navicixizumab is given on Days 1 & 15 of every 28 day cycle. This study was designed as a dose escalation trial testing navicixizumab doses of 3 or 4 mg/kg followed by an expansion cohort to enroll a total of 30 patients. The expansion cohort was undertaken with 3 mg/kg of navicixizumab as higher doses did not show increased activity, but did result in more pronounced chronic toxicity in the Phase 1a study. A standardized treatment algorithm for hypertension is being employed.

Results

Eighteen pts were treated; 5 are still ongoing. The median number of prior therapies was 4 (range 2-8), all 18 pts had received prior paclitaxel & 13 had received bevacizumab. Eight pts (44%) had a PR, 6 (33%) had SD, 2 (11%) had PD & 2 (11%) were NE. The clinical benefit rate was 78%. Ten of 14 (71%) pts with an elevated CA-125 had a GCIG-defined response. The related AEs (all grades) that occurred in > 15% of the pts were: hypertension (67%), fatigue (44%), diarrhea (44%), headache (22%), neutropenia (17%), GERD (17%) & decrease appetite (17%). Other related AEs of significance were an infusion reaction (6%), Gr2 pulmonary hypertension (6%), Gr 4 thrombocytopenia (6%) & Gr4 GI perforation (6%). Anti-drug antibody occurred in 3 of 16 pts who have been evaluated; drug exposure was impacted in 1 pt.

Conclusions

The efficacy data in these heavily pre-treated platinum resistant ovarian cancer pts are encouraging & enrollment is ongoing. The safety profile appears to be manageable with hypertension being the most common adverse event related to navicixizumab.

Clinical trial identification

NCT03030287 January 25, 2017.

Legal entity responsible for the study

OncoMed Pharmaceuticals.

Funding

OncoMed Pharmaceuticals.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.