The FDA on Thursday lifted a partial clinical hold on an early-stage study of a HER3-targeting antibody-drug conjugate that BioNTech is developing with China-based MediLink Therapeutics.
The hold, which paused enrollment, was announced in mid-June following three treatment-related deaths of cancer patients.
The companies plan to move forward with dose levels no more than 3 mg/kg, according to Monday’s announcement. The clinical trial protocol also includes “additional risk mitigation measures,” they said.
Two treatment-related deaths occurred at 4.0 mg/kg, while a third occurred at 5.5 mg/kg, according to a slide deck published by BioNTech in June. The two deaths at 4.0 mg/kg were due to sepsis from neutropenia, or abnormally low white blood cell counts, while the death at 5.5 mg/kg was due to pneumonia after Covid-19.
The trial is sponsored by MediLink and includes sites in the US and China. In the press release, BioNTech said that MediLink observed “a dose level-dependent trend” of falling white blood cell counts and an increasing rate of mucositis, or inflammation in mucous membranes. Both of which can “increase a person’s risk for developing serious infections.”
“In a new technology, in terms of dosing, we don’t know what’s the best dose level,” MediLink co-founder and chief scientist Jiaqiang Cai said Monday in an interview, noting that the HER3 antibody-drug conjugate was one of the company’s first two assets.
He added that they initially dose-escalated from 0.5 mg/kg all the way to 5.5 mg/kg, at which they saw some toxicity, and then the companies went down to 4.0 mg/kg and 4.5 mg/kg, at which they “didn’t see any very serious issues” in 28 patients.
“In the dose expansion, we recruited some more patients, and then, unfortunately, when more patients were recruited, we saw some serious toxicity,” he said.
When asked if he thought the companies escalated too quickly, Cai said, “We went too fast. Especially just around the Chinese New Year, we recruited nearly 200 patients.”
The antibody-drug conjugate, known as BNT326 or YL202, goes after HER3, which is a protein that’s overexpressed in several cancers. The Phase 1 study included certain advanced lung and breast cancer patients.
The experimental drug is currently in Phase 2 testing for a range of solid tumors as well. In October, BioNTech paid $70 million upfront to partner with MediLink on the HER3-targeting treatment. In June, FDA rejected Daiichi Sankyo’s HER3 ADC due to “findings pertaining to an inspection of a third-party manufacturing facility.” Daiichi is developing the treatment with Merck as part of a deal announced last year.
BioNTech again enlisted MediLink for a second deal in May for $25 million upfront and $1.8 billion down the road.