Phase II study of NGR-hTNF, a vascular targeting agent, in combination with doxorubicin in patients with relapsed small cell lung cancer (SCLC).

Abstract

e18043 Background: NGR-hTNF consists of tumour necrosis factor (TNF) fused to the tumour-homing peptide NGR, which selectively binds an aminopeptidase N overexpressed on tumour blood vessels. Both preclinical synergism and safe clinical toxicity profile were previously shown by using low-dose NGR-hTNF combined with doxorubicin. SCLC patients (pts) failing front-line platinum-based combination therapy are poor responders to chemotherapy. Methods: SCLC pts previously treated with at least one chemotherapy regimen received low-dose NGR-hTNF given at 0.8 μ g/m2 plus doxorubicin 75 mg/m2 every 3 weeks. NGR- hTNF was continued until progression and doxorubicin until a lifetime cumulative dose of 550 mg/m2. Primary study endpoint was the 3-month progression-free rate, with RECIST-defined tumour restaging done every two cycles. A two-stage design was used, assuming that 7/16 and 13/27 progression-free pts at 3 months would warrant further testing. Results: 16 pts (13M/3F) with a median age of 67 years (range, 41-75) were entered onto the first study stage. The number of prior treatment lines ranged from 1 to 3, whereas the median treatment-free interval was 3.0 months (95% CI, 0.8-6.6). Eleven pts presented with a PS of 0 and 5 pts with a PS of 1 or 2. In total, 55 cycles (median, 3; range, 1-10) were delivered. NGR-hTNF did not apparently modify the doxorubicin-related toxicity profile. No grade 3 to 4 NGR-hTNF-related toxicities were observed, whereas most grade 1 to 2 events were short-lived infusion-time related chills (56%). Eight pts (50%; 95% CI, 25-75%) were progression free at 3 months, thus allowing to proceed to the second study stage. The median progression-free survival was 3.0 months (95% CI, 1.8-4.2). Four partial responses (25%) and four stable diseases (25%) were observed, yielding an overall disease control rate of 50% (95% CI, 25-75%). Six pts progressed at their first restaging and 2 pts discontinued early because of symptomatic deterioration. The study is currently completing the accrual in the second study stage. Conclusions: The combination of NGR-hTNF and doxorubicin can be safely administered in pretreated SCLC pts, showing preliminary evidence of activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MolMed