Momenta Pharmaceuticals, Inc. (MNTA)

[jbog]

ASCO POSTER:

Background: Necuparanib (“necu”) inhibits multiple heparin-binding growth factors, chemokines, and adhesion molecules in nonclinical studies. It is being evaluated in a Phase 1/2 trial with nab-paclitaxel (nabP) + gemcitabine (gem) in patients (pts) with metastatic pancreatic cancer.

Updated Phase 1 safety/pharmacokinetic (PK)/pharmacodynamic (PD) data are provided.

Methods: Necu was given as daily escalating s.c. doses in combination with i.v. 125 mg/m2 nabP and 1000 mg/m2 gem (Days 1, 8, 15 of each 28-day cycle). The necu start dose was 0.5 mg/kg and was escalated until the maximum tolerated dose was determined (which was 5 mg/kg). The protocol was amended to include nabP after 2 necu + gem cohorts were completed.

Results: 39 pts in 7 cohorts (0.5 and 1 mg/kg + gem; 1, 2, 4, 6, and 5 mg/kg + nabP + gem) received necu. No new safety issues have been observed in this Phase 1 trial over the past year and no increase in known AEs of chemotherapy across doses was observed. Exposure to necu was observed starting at 2 mg/kg. Release of heparin-binding proteins (e.g. HGF, a PD marker) from heparan sulfate stores increased with dose and plateaued at 4-5 mg/kg. 3 (8%) pts remain alive; 19 (49%) pts have lived > 1 year, 8 (21%) > 1.5 years, and 4 (10%) > 2 years; 33.7 months is the longest survival to date. 16 pts treated with necu + nabP + gem completed Cycle 1 and had ≥ 1 scan on treatment; 8 (50%) achieved RECIST partial response and 6 (38%) achieved stable disease, for a disease control rate of 14/16 (88%); median overall survival (OS) in this subset was 16.0 months. Median OS of patients treated with ≥ 1 dose of necu + nabP + gem (n = 24) was 12.4 months. Of 15 CA19.9 evaluable pts, 15 (100%) had > 20%, 14 (93%) had > 50%, and 7 (47%) had > 90% decreases from baseline. Conclusions: Acceptable tolerability and encouraging signals of activity continue to be observed with the combination, which is being further evaluated in an ongoing randomized, double-blind, Phase 2 trial. Clinical trial information: NCT01621243