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Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 508
V. Gregorc1, G.L. Ceresoli2, P.A. Zucali2, F.G. De Braud3, E. Bajetta4, A. Santoro2, M.G. Viganò1, F. Caligaris Cappio1, A. Lambiase5, C. Bordignon5
1Istituto Scientifico San Raffaele, Department of Oncology, Milan, Italy
2Istituto Clinico Humanitas, Department of Oncology, Milan, Italy
3Istituto Europeo di Oncologia, Clinical Pharmacology and New Drugs Unit, Milan, Italy
4IRCCS Fondazione Istituto Nazionale dei Tumori, Department of Oncology, Milan, Italy
5MolMed, Clinical Development, Milan, Italy
Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds an aminopeptidase N overexpressed on tumor blood vessels. In preclinical models, NGR-hTNF has shown antitumor activity even at low doses.
Methods: MPM patients (pts) with radiologically-documented progression after a pemetrexed-based chemotherapy were treated with low-dose NGR-hTNF given intravenously as 1-hour infusion at 0.8 μg/m2 every 3 weeks (q3w; triweekly cohort). The trial had a 2-stage design with 16 and 27 patients to be enrolled. Primary study aim was progression-free survival (PFS) with restaging performed q6w according to MPM-modified RECIST criteria. Subsequently, an additional 14 pts were treated at 0.8 μg/m2 on a weekly basis (weekly cohort).
Results: In the triweekly cohort, 43 pts were evaluated over 170 cycles (range, 1–18). Patient characteristics were: median age 64 years (range, 54–80); male/female 27/16; epithelial/nonepithelial histology 34/9; PS 0/1/2 24/10/9; EORTC score good/poor 34/9. Only one grade 3 drug-related toxicity was observed. Main grade 1–2 toxicities were short-lived chills (71%), arising during the first infusions. The median and 3-month PFS were 2.8 months (95% CI, 1.9–3.7) and 43% (95% CI, 28–58), respectively. The disease control rate (DCR) was 44%. One patient (2%) had a partial response lasting 10.0 months and 18 patients (42%) maintained stable disease (SD) for a median time of 4.3 months (range, 2.2–13.7 months). With a median follow-up of 19.6 months, the median and 1-year overall survival (OS) were 11.6 months and 48%, respectively. Median OS in pts who achieved DCR and in those who did not were 13.3 and 8.3 months, respectively. In the weekly cohort, 242 infusions were delivered (range, 4 to 45 cycles) and 5 pts (36%) received ≥30 weekly cycles. There was no toxicity exacerbation. Seven pts (50%) experienced SD for a median time of 8.1 months (range, 2.4–11.4+). The 6- and 12-month PFS rates were 36% and 19%, respectively. In the overall study population (n = 57), the DCR was 46% (95% CI, 34–59), the median duration of DCR was 4.7 months (95% CI, 4.0–5.3), and the median OS was 13.1 months (95% CI, 9.1–17.1).
Conclusion: NGR-hTNF 0.8 μg/m2 weekly is well tolerated, showing promising disease control in previously treated MPM patients, and will be further developed in this setting.
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