Randomized, blinded, placebo-controlled phase II trial of docetaxel and bavituximab as second-line therapy in locally advanced or metastatic non-squamous non-small cell lung cancer.

Abstract

8095 Background: Bavituximab (B) is a monoclonal antibody against phosphatidylserine (PS) with a selective tumor vascular-directed immune response. The purpose of this trial is to evaluate the efficacy and safety of B or placebo (P) combined with docetaxel (D) in patients with locally advanced or metastatic non-squamous NSCLC. Methods: Patients were randomized 1:1:1 to receive 75 mg/m2 of D every 21 days for up to 6 cycles combined with weekly blinded infusions of P, 1mg/kg B or 3 mg/kg B until disease progression or unacceptable toxicity. Primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). Safety was evaluated by adverse events (AEs), vital signs, CBC, biochemistry, urinalysis, coagulation, ECG. Post study unblinding, a PK substudy revealed vial coding discrepancies in the P and 1 mg/kg vials. As a result, data from these two groups were pooled to form the control (C) arm in the analysis. Results: Forty-one patients were entered into the 3mg/kg B+D arm and 80 into the control arm. No significant differences were seen in age, gender, ethnicity or disease stage. ECOG 2 was 13% in C and 24% in 3 mg/kg B+D arms. At this analysis, 54% death events have been reported in 3 mg/kg B+D and 71% in C arm. ORR is 17.1%/13.8% and median PFS is 4.5/3.3 months for 3 mg/kg B+D/C. Median OS is 11.7 months for 3 mg/kg B+D and 7.3 months for C. The safety profile for 3 mg/kg B+D was similar to that of C in severity and frequency. No other safety signal was identified. Conclusions: This randomized, placebo-controlled phase 2 trial demonstrated a positive trend favoring 3 mg/kg B+D in ORR, PFS and OS. 3 mg/kg B in combination with D was well tolerated and is the planned dose forPhase 3. Clinical trial information: NCT01138163.