Molecular Templates, Inc. (Nasdaq: MTEM, “Molecular Templates,” or “MTEM”),  announced that the U.S. Food and Drug Administration (the “FDA”) informed MTEM that it has placed a partial clinical hold on the Phase 1 study of MT-0169 based on previously disclosed cardiac adverse events noted in two patients dosed at 50 mcg/kg that prompted the dose reduction to 5 mcg/kg last year. Since then, four patients have been dosed at 5 mcg/kg and three patients have been dosed at 10 mcg/kg with no cardiac adverse events noted.

Of the patients dosed at 50 mcg/kg, one patient experienced asymptomatic grade 2 myocarditis and one patient experienced asymptomatic grade 3 cardiomyopathy; both patients had full recoveries within two months of these events. No grade 4 or 5 toxicities were observed at 50 mcg/kg. Under the partial clinical hold, current study participants may continue treatment, but no new patients will be enrolled until the partial hold is lifted by the FDA.

After filing a protocol amendment in January 2022, Molecular Templates resumed study treatment in patients with relapsed Multiple Myeloma at 5 mcg/kg, a 90% reduction in dose. Four patients were dosed at 5 mcg/kg with no adverse events greater than grade 1 noted and no cardiac adverse events noted. One patient dosed at 5 mcg/kg had a Very Good Partial Response (“VGPR”) that deepened to a stringent complete response and remains on study for more than 7 months. Three patients were dosed at 10 mcg/kg with no cardiac events noted; one patient dosed at 10 mcg/kg experienced transient grade 2 diarrhea.  

The FDA has asked MTEM to provide narratives on the two patients who experienced cardiotoxicity at 50 mcg/kg, justification for the revised dose of 5 mcg/kg, and data evaluating the clinical benefit-to-risk ratio seen with the lower doses of MT-0169, among other requests.

"Patient safety is our highest priority. The 5 and 10 mcg/kg cohorts have been completed and we have not observed any cardiac adverse events or other serious adverse events at these lower doses. One patient dosed at 5 mcg/kg is in a stringent complete response and is in his seventh month of therapy. We look forward to sharing these data with the FDA and are confident in the benefit-risk profile of MT-0169 at these lower doses," said Roger Waltzman, MD., Chief Medical Officer at MTEM. "We are excited to see early signs of clinical benefit in this difficult-to-treat patient population."