U3-1565 / Daiichi Sankyo - LARVOL DELTA

Phase I study of the anti-heparin binding-EGF antibody U3-1565 with cetuximab in patients with cetuximab- or panitumumab-resistant metastatic colorectal cancer (AACR 2018) - "On the other hand, re-challenge with anti-EGFR antibodies may have some clinical benefits.PATIENTS AND METHODS This phase I study of combination therapy of U3-1565 (a fully human anti-HB-EGF antibody) and Cmab enrolled patients with KRAS-wild type metastatic colorectal cancer who had received 2≤ regimens with fluoropyrimidine, oxaliplatin, irinotecan and Cmab/Pmab and had disease progression on Cmab/Pmab. No correlation was observed between pre-treatment serum HB-EGF level and the efficacy, while serum HB-EGF level on day 8 in the first cycle decreased lower than the measurement sensitivity in all patients.CONCLUSIONS The RD of this combination therapy was determined to be biweekly infusion of U3-1565 at a loading dose of 24mg/m2 followed by 16mg/ m2 and Cmab at a loading dose of 400mg/m2 followed by 250mg/ m2. The efficacy of this combination therapy after progression on Cmab/Pmab was modest."

Clinical • P1 data • Colorectal Cancer

First-in-human study of the anti-HB-EGF antibody U3-1565 in subjects with advanced solid tumors. (PubMed, Invest New Drugs) - "Subjects with high VEGF-A baseline levels remained on treatment longer (3/6 entered study extension phase versus 1/30), and were more likely to show disease control (3/6 versus 4/30). In conclusion, U3-1565 demonstrates both proof of mechanism and clinical activity across different tumor types."

Clinical • Journal • P1 data

Phase I study of the anti-heparin-binding epidermal growth factor-like growth factor antibody U3-1565 with cetuximab in patients with cetuximab- or panitumumab-resistant metastatic colorectal cancer. (PubMed, Invest New Drugs) - "This phase I study of U3-1565, anti-HB-EGF antibody, and Cetu combination therapy enrolled patients with KRAS wild-type metastatic colorectal cancer who had received two ≤ regimens with fluoropyrimidine, oxaliplatin, irinotecan, and Cetu/Pani and had disease progression on Cetu/Pani. The efficacy of this combination therapy after progression on Cetu/Pani was negligible. Trial Registration: UMIN000013006."

Clinical • Journal • P1 data