April 25, 2019
Translational Research in Oncology (TRIO), a global academic clinical research organization, today announced it has partnered with Molecular Templates (Nasdaq: MTEM) to conduct its First-in-Human study for patients with previously treated advanced HER2-positive solid tumors.
This Phase I first-in-human study is an open-label, dose escalation and expansion study of MT-5111 given as monotherapy in subjects with HER2-positive solid tumors. The primary objective of the trial is to evaluate the safety and tolerability and determine the recommended Phase II dose of MT-5111 in subjects with advanced HER2-positive solid tumors.
“We are pleased to partner with Molecular Templates to bring their research into the clinical setting”, says Launa Aspeslet, PhD, CEO of TRIO. “Our extensive experience in cancer trials coupled with strong investigator relationships, proven operational expertise and commitment to high-quality data makes TRIO the ideal partner to advance MT-5111.”
“The depth of experience in the HER2 space that TRIO can offer due to its academic leadership and scientific committee make them a natural fit to coordinate this trial”, added Dennis Slamon, MD, PhD, TRIO Chairman/Executive Director and Director of Clinical Translational Research at the University of California, Los Angeles Jonsson Comprehensive Cancer Center. “The translational research model is the best path to bringing innovative products, like Molecular Templates’ MT-5111, to the market.”
“Molecular Templates is delighted to be partnering with TRIO to conduct a Phase I study for MT-5111,” said Roger Waltzman, MD, Chief Medical Officer of Molecular Templates. “We have seen promising responses with our lead pipeline candidate MT-3724 in DLBCL and we are excited to further leverage the novel mechanism of action of our ETB platform with MT-5111 to potentially benefit patients with HER2 positive cancers including breast and gastric cancers.”
About MT-5111
MT-5111 is an ETB consisting of a single chain variable fragment (scFv) with affinity for HER2, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA). MT-5111 specifically binds and kills HER2 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity. MT-5111 has been specifically designed to avoid competition with and to overcome the primary mechanisms of tumor resistance to current HER2 targeted therapies. To accomplish this, first, MT-5111 binds a HER2 domain that is distinct from the trastuzumab and pertuzumab binding sites, which results in MT-5111 HER2-mediated binding and cell kill even in the presence of these monoclonal antibodies. As such, MT-5111 may have the potential to be combined with other HER2 targeted therapies. Second, SLTA is a large molecule protein and is not a substrate of drug efflux transporters such as MDR1 which has been demonstrated to be one of the primary mechanisms of resistance to the antibody drug conjugate, T-DM1. Third, MT-5111 mediated ribosomal inhibition and cell death take place intracellularly so changes in the tumor microenvironment which inhibit immune-mediated mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) are not expected to inhibit MT-5111 activity. Finally, mutations to the HER2 kinase domain that can induce constitutive downstream signaling to drive tumor proliferation are not expected to interfere with MT-5111 activity given that its mechanism of action is not dependent upon kinase domain binding and MT-5111 works directly on ribosomes to mediate ribosomal inhibition and cell death. Together, MT-5111 represents a novel HER2 targeted therapy which could provide benefit in subjects with HER2-positive cancers and potentially overcome mechanisms of tumor resistance to existing HER2 targeted therapies.