Two Doses Of Ngr-Htnf Combined With Capecitabine/Oxaliplatin (Xelox) In Colorectal Cancer (Crc) Patients Failing Standard Regimens: A Phase Ii Study

e14077 Background: NGR-hTNF consists of tumour necrosis factor (TNF) fused to the tumour homing peptide (NGR), which selectively binds an aminopeptidase N expressed on tumour blood vessels. Preclinically, NGR-hTNF showed a biphasic dose-response curve. Phase I trials previously selected 0.8 μg/m2 and 45 μg/m2 as optimal-biological and maximum-tolerated dose, respectively. Methods: Two sequential cohorts of 12 CRC patients (pts) failing standard therapies were planned to receive NGR-hTNF given at 0.8 μg/m2 (LD) or at 45 μg/m2 (HD) as 1 hour infusion every 3 weeks (q3w). XELOX included capecitabine 825 mg/m2 twice daily for 14 days and oxaliplatin 100 mg/m2 q3w. Safety was the primary aim of the study (< 2/12 pts with grade 3-4 NGR-hTNF-related toxicity). Results: 12 pts were enrolled in the LD cohort and 12 pts in the HD cohort. All but 2 pts had previously received chemotherapy, whereas 9 pts in LD and 10 pts in HD were pretreated also with biologicals. The median number of prior regimens was 3 in LD and 2 in HD. 44 and 35 cycles were delivered in LD and HD, respectively. The combination was well tolerated: no grade 3-4 NGR-hTNF-related toxicities were noted in both cohorts. Most related toxicities were grade 1 to 2 chills experienced by 10 pts during 19 cycles in LD and by 7 pts over 14 cycles in HD. In the LD cohort, one pt (8%) had a partial response and 5 pts (42%) had stable disease for a median duration of 5.0 months (range, 3.0–5.5). In the HD cohort, 4 pts (33%) had stable disease for a median time of 4.1 months (range, 3.0–6.1). For the whole study population, the 3- and 6-month progression-free survival (PFS) rates were 48% (95% CI, 28–69) and 38% (15– 65), respectively. Two pts in the LD cohort experienced PFS times longer than the PFS of prior therapy lines. Conclusions: Both NGR-hTNF doses were safely administered in combination with XELOX in heavily pretreated CRC pts. A hint of activity was apparent with LD NGR-hTNF. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MolMed