Top-line results from SUNRISE: A phase III, randomized, double-blind, placebo-controlled multicenter trial of bavituximab plus docetaxel in patients with previously treated stage IIIb/iv non-squamous non-small cell lung cancer

Background: Exposed phosphatidylserine (PS) in the tumor microenvironment is highly immunosuppressive. Bavituximab targets PS and repolarizes M2 macrophages to M1 resulting in production of pro-inflammatory cytokines such as IFN-γ and IL-12, maturation of dendritic cells, and tumor specific cytotoxic T lymphocyte immunity. In a prior blinded Phase II trial in 2nd-line nonsquamous NSCLC, bavituximab + docetaxel was well-tolerated and demonstrated 60% improvement (11.7 vs 7.3 months) in median overall survival (mOS) (HR, 0.66; P = 0.11) compared to control. Methods: 597 patients with Stage IIIb/IV nonsquamous NSCLC that progressed on platinum-doublet chemotherapy were randomized 1:1 to receive up to six 21-day cycles of docetaxel in combination with weekly 3 mg/kg bavituximab (B+D) or placebo (D) until progression or toxicity. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results: With 12 months follow-up from the last patient randomized and ∼85% of the targeted OS events reached, mOS was 10.5 months (95% confidence interval [CI], 8.4-11.9) among 297 patients in B+D and 10.9 months (95% CI, 9.2-12.1) among 300 patients in D (HR, 1.06; P = 0.533). PFS was 4.2 months (95% CI, 3.9-4.6) in B+D and 4.1 months (95% CI, 3.2-4.8) in D (HR, 1.02; P = 0.876). The ORR was 15% in B+D vs. 11% in D (odds ratio, 0.7; P = 0.15). The safety profile was similar between groups. Grade 3 or higher adverse events occurred in 68% of patients in B+D and 60% in D. In an exploratory analysis of OS for patients who received subsequent immune checkpoint inhibitors (ICI), the mOS was not reached (95% CI, 15.2-NA) in B+D (n = 46) and 12.6 months (95% CI, 10.4-17.8) in D (n = 47) (HR, 0.46; P = 0.006). Conclusions: The combination of B+D was well-tolerated though no OS difference was observed compared to D alone in the ITT population of previously treated nonsquamous NSCLC. An exploratory analysis of patients who received subsequent ICI found significantly longer OS in patients who received prior B+D than those who received D and support further clinical investigation of B+ICI in NSCLC. Clinical trial identification: NIH = NCT01999673 EudraCT = 2013-003953-13 Legal entity responsible for the study: Peregrine Pharmaceuticals Inc. Funding: Peregrine Pharmaceuticals Inc. Disclosure: P. Bidoli: Eli Lilly personal fees and advisory board BMS personal fees and advisory board Boehringer personal fees and advisory board. M. Reck: Honoraria for lectures and consultancy with Hoffmann-La Roche, Lilly, MSD, Merck, BMS, AstraZeneca, Celgene, Boehringer-Ingelheim, Pfizer, Novartis. N. Kallinteris, J. Lai: Peregrine Pharmaceuticals Inc. = employee, stock ownership M. Tang: Peregrine = Employee, stock owner. J. Shan: Employee, officer and stock owner for Peregrine Pharmaceuticals Inc. All other authors have declared no conflicts of interest.