PHASE II STUDY OF NGR-HTNF, A NOVEL VASCULAR TARGETING AGENT (VTA), ADMINISTERED AS SINGLE AGENT AT LOW DOSE IN PATIENTS (PTS) WITH COLORECTAL CANCER (CRC) REFRACTORY TO STANDARD REGIMENS

4110 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13 highly expressed on tumour blood vessels. NGR-hTNF combines activity on tumour vascular permeability and direct anticancer activity. In preclinical models, NGR-hTNF showed antitumor activity at both low and high doses. Methods: Pts with CRC refractory to standard treatments, including biological agents, were enrolled to evaluate a low dose of NGR-hTNF given at 0.8 mcg/m2 as 1-hour intravenous infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled in stage 1 and 2, respectively. Progression-free survival (PFS) was the primary end point and reassessment was performed q6w. Results: 32 pts (16 M/16 F; PS 0/1 26/6; median age: 65 years, range 53–79) received 111 cycles (median 2, range 1–10) and 13 pts (41%) were treated with ≥4 doses. The median number of prior regimens was 3 (range: 2–5), with 8 pts (25%) pre-treated with ≥4 lines. In the first stage, one pt (6%) achieved a confirmed partial response lasting 5 months and 9/16 pts (56%) had a stable disease (SD). The median and 3-month PFS were 2.9 months (95% CI 1.9–3.9) and 47% (95% CI 21–71%), respectively. After completion of the second stage, a total of 4 pts were progression-free at 4.5 months, with one pt still on treatment after 7 months. Neither grade 3–4 treatment-related adverse events nor toxicity- related death were observed. Main grade 1–2 toxicities per patient were infusion-related chills (41%) and transient blood pressure increase (9%). The study is currently recruiting patients into a subsequent cohort of 12 patients treated with a weekly schedule of administration. Conclusions: Based on the favourable and manageable toxicity profile and preliminary evidence of activity in heavily pretreated CRC patients, NGR-hTNF will be further developed both as single agent and in combination with standard chemotherapeutics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Molmed