BioNTech partner MediLink Therapeutics can resume enrollment of a Phase 1 clinical trial testing an antibody-drug conjugate in people with lung and breast cancer, BioNTech said Monday, after the Food and Drug Administration removed a partial hold related to immune-related side effects.
Trial investigators will limit dosing of the drug, dubbed BNT326, to 3 milligrams per kilogram of body weight to reduce cases of suppressed white blood cell counts and mucositis, an inflammation of the digestive tract. People who had been enrolled in groups scheduled to receive a higher dose will now get the 3 milligram infusion, BioNTech said.
A review of safety data had shown a “dose-dependent” increase in the incidence of those side effects, prompting the dose limitation, BioNTech said. Those side effects are common in existing chemotherapies and are typically managed with dose reductions or interruptions, or use of a type of biological drug that boosts white blood cell production.
At 3 milligrams per kilogram, “the safety profile was manageable and encouraging clinical activity was observed,” BioNTech said.
BNT326 combines an antibody that binds with a protein called HER3 that is expressed in some types of breast and lung cancer. After binding with tumor cells, the drug releases a toxic chemotherapy.
When BioNTech announced the partial hold on June 17, it cited “safety findings including grade 5 adverse events,” a term trial investigators typically use to describe deaths from side effects. Data presented at a medical meeting earlier that month noted the deaths of three trial participants given doses higher than 3 mg/kg.
BioNTech licensed the drug last year from China-based MediLink for an upfront fee of $70 million and promises of additional milestone payments worth up to $1 billion. The deal followed an expansion by the German biotech, which has largely focused on RNA medicines, into ADCs, including a deal with another China-based company called Duality Biologics.
Editor’s note: This story has been updated with additional information regarding the trial deaths.
