Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 340

L. Rimassa¹, A. Santoro¹, A.F. Sobrero², F. Sclafani¹, V. Gregorc³, V. Andretta², M.C. Tronconi¹, F. Caligaris Cappio³, A. Lambiase⁴, C. Bordignon<sup>4

1</sup>Istituto Clinico Humanitas, Department of Oncology, Milan, Italy
²Ospedale San Martino, Department of Oncology, Genoa, Italy
³Istituto Scientifico San Raffaele, Department of Oncology, Milan, Italy
⁴MolMed, Clinical Development, Milan, Italy

Background: NGR-hTNF is a VTA consisting of TNF-a fused to the tumor-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumor blood vessels.
Methods: CRC pts failing standard therapies received low-dose NGR-hTNF given at 0.8 μg/m² as 1-hour infusion every 3 weeks (q3w; triweekly cohort). Progression-free survival (PFS) was the primary study objective with restaging performed q6w. A 2-stage design was used, with 16 and 27 pts to be recruited. Ultimately, an additional 13 pts were treated with 0.8 μg/m² on a weekly basis (weekly cohort).
Results: In the triweekly cohort, 111 cycles (range, 1–10) were delivered to 33 pts with radiologically-documented progression after last therapy. Pts characteristics were: median age: 65 years (range, 53–79); M/F 16/17; PS 0/1 26/7. Median number of prior lines was 3 (range, 2–5), whereas 8 pts (25%) had received ≥4 lines and 22 (67%) biologicals. No grade 3–4 drug-related toxicity was observed. Predominant grade 1–2 toxicities were short-lived, infusion-related chills (53%). The median PFS was 2.5 months (95% CI, 2.2–2.8) and the PFS rates at 3 and 4.5 months were 31% and 16%, respectively. The disease control rate was 39% (95% CI, 23–55), with one partial response (3%) and 12 stable diseases (36%). In pts with disease control, the median PFS time was 3.8 months and the 3- and 4.5-month PFS rates were 67% and 42%, respectively. With a median follow-up of 18.4 months (95% CI, 18.3–18.5), the median OS time was 13.1 months (95% CI, 8.7–17.5). The proportions of pts alive at 18 and 24 months were 33% and 25%, respectively. Pts who achieved disease control had a median OS of 15.4 months, while those who did not had 9.3 months. Median OS in pts pretreated with <3 and ≥3 regimens were 18.6 and 9.3 months (p = 0.03), respectively, whereas 1-year survival rates in biological-naïve and prior-biological pts were 72% and 41% (p = 0.01), respectively. There was no toxicity exacerbation using the weekly schedule. In this cohort, two patients (15%) had PFS of 10.5 and 11.0 months, which resulted longer than PFS on prior therapy (3.8 and 6.3 months, respectively).
Conclusion: Based on favourable toxicity profile and disease control in heavily pre-treated CRC patients, NGR-hTNF will be further developed in combination with standard chemotherapy.