A phase Ib safety and pharmacokinetic study of bavituximab plus chemotherapy in patients with refractory advanced solid tumor malignancies

Abstract

3038 Background: Bavituximab (B) is a first in class anti-phosphatidylserine (PS) monoclonal antibody. This immunotherapeutic agent selectively binds to PS exposed on tumor blood vessels causing an enhanced immune response and shutting down blood flow into the tumor. Pre-clinical data suggest a synergistic action using anti-PS antibodies in combination with chemotherapy. Methods: This was an open-label, non- randomized, multi-center study in pts with refractory advanced solid tumors. B was given weekly for up to 8 weeks, at a dose of 3mg/kg i.v., in combination with docetaxel (D)(75–80mg/m2 every 3 weeks) or gemcitabine (G) (1,000mg/m2 weeks 1–7) or paclitaxel (175mg/m2 every 3 weeks) plus carboplatin (AUC=5) (P+C). Study objectives were to assess safety and tolerability of B and to characterize its PK profile when used in combination with chemotherapeutic agents. Serum levels of B were determined by ELISA. Results: 14 pts were enrolled, mean age was 48.4yr, 78.6% were female. All had a stage IV tumor. 5 pts received B+D, 5 pts received B+G and 4 pts received B+P+C. Pts received a mean of 6 doses of B. AEs were reported by 13 pts. Most common were vomiting (6pts), cough (4 pts), asthenia, pain, headache, neutropenia, prolonged aPTT and pain in extremities, each in 3pts. 3 pts reported SAEs considered to be related to B, 1 pt had non-related SAE. On Days 0 and 21, no significant differences in PK characteristics were seen between the three treatment groups following administration of B. No accumulation of B was seen following multiple dose administration. Using RECIST criteria, week 8 tumor responses were PR (3pts), SD (3pts) and PD (6pts); 2 pts were non-evaluable. Conclusions: The PK of B was not impacted by co-administration of conventional chemotherapy. 50% of all evaluable pts achieved an objective tumor response or stable disease. These findings warrant further efficacy studies of B in pts with refractory solid tumors. Treatment Arm Day 0 (Dose 1) Day 21 (Dose 4) Cmax (μg/mL) Tmax (hr) AUCinf (μ*hr/mL) T1/2 (hr) Cmax (μg/mL) Tmax (hr) AUCinf (μ*hr/mL) T1/2 (hr) B+D 47.5 5 3303 25.5 40.7 2.5 3421 27.9 B+G 56.2 5 4354 26.5 44.6 2.5 4083 28.3 B+P+C 58.5 4.25 3835 25 58.7 1.75 4446 24.4 Values shown are medians Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc.