A Phase 2 Study Evaluating Axitinib in Patients With Unresectable, Recurrent, or Metastatic Head and Neck Cancer

Abstract

In combination with IR, M3814 showed efficacy in all of the 6 mouse models of human cancer as demonstrated by a strong potentiation of the effect of IR. In all models, a dose of 2 Gy administered daily for 1 week in combination with M3814 induced statically significant tumor growth inhibition compared to IR alone. In 2 models, FaDu and NCI-H460, M3814 induced tumor regression. In the FaDu model, no tumor regrowth (duration of the experiment >100 days) was observed in the combination arm with IR (2 Gy per fractions, 6 weeks, 5 days per week: total dose 60 Gy) at the doses of 25 and 50 mg/Kg. In the IR only arm, no tumor responses were observed. These effects were a likely consequence of inhibiting DNA-PK activity, as shown by measuring the autophosphorylation of DNA-PK in FaDu tumor tissue. M3814, alone or in combination with IR, did not induce significant weight loss or visual signs of toxicity in the mice in any study. Conclusion: M3814 is active in nonclinical experiments in combination with IR. Strong antitumor activity was observed in several xenograft models with complete regressions of tumors upon application of the established clinical IR schedule of 2-Gy fractions for 6 weeks in the FaDu model (squamous cell carcinomas of the head and neck). Clinical evaluation of M3814 is ongoing.

Antiangiogenic agents in head and neck squamous cell carcinoma: Tired of going solo

“…However, antiangiogenic agents primarily targeting VEGF have disappointingly failed to demonstrate meaningful clinical activity in R/MSCCHN and can be associated with a risk of significant toxicity. Single‐agent phase 2 trials of oral multikinase VEGF receptor (VEGFR) inhibitors in R/MSCCHN have demonstrated low‐to‐modest antitumor activity (sorafenib: objective response rate [RR], 3.7%; disease control rate [DCR], 37%; sunitinib: RR, 2.6%; DCR, 50%; axitinib: RR, 0%; DCR, 77%; and no significant improvement in progression‐free survival [PFS]).…”