Three ETBs (MT-0169, MT-5111, and MT-6402) are currently in clinical studies across different targets (CD38, HER2, PD-L1) and across hematologic malignancies, solid tumor, and immuno-oncology indications. ETBs can also deliver additional payloads to drive unique biology like the alteration of tumor immunophenotype. Here we describe three active clinical stage programs with encouraging safety and efficacy data that represent a transformation of the immunotoxin landscape into a more viable therapeutic approach to target validated as well as typically intractable clinical cancer targets.
These cytokines overlap with cytokine signatures observed after dosing MT-6402 in HLA:A*02 patients. Preclinical assessment of the safety profile of candidates is ongoing and further development is slated for 2021.
Introduction MT-6402 is a de-immunized engineered toxin body (ETB) targeting PD-L1 for solid tumors that carries a Shiga-like Toxin-A (SLT-A) payload with the addition of cytomegalovirus (CMV) antigen seeding technology (AST)...In Part A, the starting dose will be 16 µg/kg based upon the highest non-severely toxic dose in non-human primates; in Part B, the starting dose will be the MTD determined in Part A. Treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, or another reason. Enrollment is estimated to begin at several US centers in the first half of 2021.
MT-6402 delivers a powerful and unique dual mechanism of action. The combination of a PD-L1 specific direct cell kill and redirection of a robust effector T cell response to the tumor has potential benefit in solid tumor indications, including in the relapsed setting, when disease has progressed after checkpoint and/or other therapies.