Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 395

A. Santoro¹, G. Citterio², T. Pressiani¹, V. Gregorc², L. Rimassa¹, F.G. De Braud³, G. Rossoni², F. Caligaris Cappio², A. Lambiase⁴, C. Bordignon<sup>4

1</sup>Istituto Clinico Humanitas, Department of Oncology, Milan, Italy
²Istituto Scientifico San Raffaele, Department of Oncology, Milan, Italy
³Istituto Europeo di Oncologia, Clinical Pharmacology and New Drugs, Milan, Italy
⁴MolMed, Clinical Development, Milan, Italy

Background: HCC is a highly vascularised tumor with a median survival of 6 months reported in untreated pts with advanced disease class C according to Barcelona Clinic Liver Cancer (BCLC) staging. NGR-hTNF is a VTA consisting of TNF-a fused to the tumor-homing peptide NGR, which binds an aminopeptidase N overexpressed on tumor vessels.
Methods: Advanced-stage HCC pts received NGR-hTNF 0.8 μg/m² infused over 1-hour every 3 weeks (q3w). Progression-free survival (PFS) was the primary study aim with restaging performed q6w. A two-stage design was used with 16 and 27 pts to be enrolled. Subsequently, an additional 12 pts were treated with 0.8 μg/m² on a weekly basis (weekly cohort).
Results: Pts with documented progression after loco-regional treatments (59%), systemic therapies (56%; range, 1–3 regimens), or both (33%) received 90 cycles (range, 1–18+). Pt characteristics were: median age 65 years (range, 34–79); M/F 21/6; PS 0/1 18/9; Child-Pugh (C-P) A/B 21/6, BCLC B/C 5/22. No grade 3–4 drug-related toxicities were observed. Main grade 1–2 toxicities were short-lived, infusion-related chills (55%). The median PFS was 2.3 months (95% CI, 1.7–2.9). The disease control rate (DCR) was 30% and the confirmed response rate was 8%. A complete response (4%) lasting 11.5+ months was observed in a 76-year-old sorafenib-refractory, C-P B pt. A partial response (4%) with a 78% tumor reduction was reported in a further C-P B pt. Additionally, a 28% tumor shrinkage was detected in one out of 6 patients (22%) experiencing stable disease. Pts who achieved disease control received a median of 5 cycles (range, 4–18+) and had a median PFS of 4.3 months (range, 3.0–12.8+). With a median follow-up of 14.0 months (95% CI, 12.7–15.3), 8 pts (30%) were still alive and the median overall survival (OS) time was 9.1 months (range, 1.3–21.3+). The survival rates at 12 and 18 months were 34% and 22%, respectively. In the weekly cohort, there was no worsening of toxicity and the DCR was 33%. The subset of 12 sorafenib-pretreated pts reported a response rate of 8% and a DCR of 33%, whereas the median PFS and OS were 2.3 and 9.5 months, respectively.
Conclusions: NGR-hTNF is well tolerated and appears to have promising antitumor activity in previously treated HCC patients. The drug will be further developed in this setting.