The first patient has been dosed in a Phase 1 clinical trial testing the safety and efficacy of the CD38-targeting therapy TAK-169 in people with relapsed or refractory multiple myeloma, Molecular Templates (MTEM) announced.
TAK-169, developed by MTEM in partnership with Takeda, is an engineered toxin body — a kind of targeted biologic therapy that binds a cancer protein and is internalized into cells, where it stops key cellular machinery and causes cancer cell death.
The investigative therapy contains an antibody fragment targeting CD38, a protein found in high levels on the surface of myeloma cells. It is fused to a Shiga-like toxin A-subunit (SLTA), a bacterial protein that, once inside malignant myeloma cells, irreversibly blocks the protein-making machinery of the cell and kills it.
Importantly, the SLTA protein in TAK-169 is engineered in a way that allows it to escape the immune system.
TAK-169 has demonstrated a potent cell killing ability in multiple myeloma cell lines and in patient-derived cells. It also has induced complete tumor regressions in mice models of the disease — either as a once-weekly treatment or every two weeks — and its repeat dosing in non-human primates has been shown to be well-tolerated at doses believed to be effective.
The ongoing Phase 1 trial (NCT04017130) is a dose-escalation, dose-expansion study designed to assess the safety, tolerability, and preliminary signs of effectiveness of TAK-169. The participants are multiple myeloma patients who are refractory, or failed to respond to treatments with at least one proteasome inhibitor, one immunomodulatory agent, and one steroid.
The study will be divided in two parts. The dose-escalation part will enroll 39 to 60 patients and treat them with ascending doses of TAK-169. The first group will receive a weekly dose of 50 microgram per kilogram (mcg/kg). If no major safety issues are observed, the researchers will increase the dose of TAK-169 to 100, 200, 335, 500, and 665 microgram per kilogram once weekly on subsequent groups of participants.
The goal is to establish the maximum tolerated dose and to identify the optimal dose for additional testing. Based on preliminary data, TAK-169 also may be tested as a once-every-two-weeks treatment.
After an optimal dose has been established, the study will recruit an additional 54 patients and include them in one of two groups: a group that has never received the CD38-targeting antibody Darzalex (daratumumab), and a group that has failed treatment with that antibody.
In this part, the main goal is assessing preliminary signs of efficacy by determining the proportion of patients who respond to treatment. Secondary goals include duration of response, time to disease progression or death, and overall survival.
Pharmacokinetics, or how a drug is metabolized in the body, and pharmacodynamics, or how the body is affected by that drug, will be assessed as secondary endpoints. Another secondary endpoint will be determining any unwanted immune responses targeting TAK-169.
The study will last 34 months and patients will be followed up for 30 days after taking their last dose.
TAK-169 “represents a promising therapeutic approach for multiple myeloma patients with significant unmet medical needs,” Eric Poma, PhD, Molecular Templates’ CEO and scientific officer, said in a press release.
“We are pleased that dosing is underway in the Phase I study,” Poma said. “This product candidate is designed to deliver a potent, direct, cell-killing mechanism to cells that express CD38, a receptor that is known to be central to myeloma disease.”
The start of patient dosing in this Phase 1 study is a milestone that will trigger a $10 million payment from Takeda to Molecular Templates, the company said.
“This program is a prime example of Takeda’s emphasis on working with world-class partners to discover and develop transformational new therapies for multiple myeloma and other hematologic malignancies,” said Chris Arendt, PhD, head of the oncology therapeutic area unit at Takeda.
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