Supplementary Material for: Anexelekto (Axl)/Mer inhibitor tamnorzatinib in patients with relapsed/refractory acute myeloid leukaemia: Results from a phase I (monotherapy) and phase II (combination with venetoclax) clinical study

Introduction: Relapsed/refractory (R/R) acute myeloid leukaemia (AML) is a life-threatening haematological malignancy without effective treatments. Anexelekto (Axl) and Mer receptor tyrosine kinases have emerged as important therapeutic targets in AML for their crucial role in survival of AML cells. Tamnorzatinib (ONO-7475) is a potent and highly selective inhibitor of Axl/Mer. We report first-in-human study of tamnorzatinib (NCT03176277) in patients with R/R AML.
Methods: Tamnorzatinib was administered as monotherapy (n=20) to determine an appropriate biological dose of tamnorzatinib and then in combination (n=22) with venetoclax to evaluate safety and clinical efficacy.
Results: Tamnorzatinib was safe and well tolerated as monotherapy (3, 6, and 10 mg) and in combination (6 mg) with venetoclax. No dose-limiting toxicities were observed at any dose level. Near-maximal Axl/Mer inhibition was observed following 6 mg tamnorzatinib alone and in combination therapy. No complete remission (CR) or CR with partial hematologic recovery was observed with combination therapy. However, decreased transfusion dependency was observed; in the venetoclax-resistant subgroup (n=14), 1 patient (7.1%) achieved CR with incomplete hematologic recovery and 1 patient (7.1%) achieved morphologic leukaemia-free state.
Conclusion: Tamnorzatinib alone and in combination with venetoclax was safe and well tolerated but failed to induce robust clinical efficacy in R/R AML.