The FDA has allowed MediLink Therapeutics to restart a phase 1 trial of its BioNTech-partnered antibody-drug conjugate (ADC) that saw three fatalities after the companies confirmed that only lower doses will be used.
The agency put the trial on hold in mid-June, with BioNTech explaining at the time that the decision was linked to concerns that the candidate, dubbed BNT326/YL202, “may, at higher doses, expose human subjects to unreasonable and significant risk of illness or injuries.”
In a presentation at the American Society of Clinical Oncology (ASCO) earlier that month, the German drugmaker had referred to two deaths from the fifth-dose cohort and one death in the seventh-dose group. BioNTech had already made the call to focus on doses below 4 mg/kg, it added in the presentation, “where the safety profile was manageable and promising clinical activity was observed.”
This morning, the biotech confirmed that it will focus solely on doses no higher than 3 mg/kg. The company said its partner MediLink "had observed a dose level-dependent trend of treatment-related adverse events (TRAEs) of BNT326/YL202, in particular neutrophil count decrease and an increasing rate of mucositis events,” BioNTech explained.
These events are common side effects of chemotherapies and increase the risk of developing serious infections, the company pointed out.
“Based on emerging safety data from the ongoing trial evaluating BNT326/YL202, the companies swiftly and proactively took precautionary measures, including not enrolling additional patients in dose cohorts higher than 3 mg/kg, and reducing dose levels for participants already enrolled at higher dose levels in the trial,” BioNTech added.
“In parallel, MediLink has notified the FDA and worked with BioNTech on analyzing the emerging data and implementing further risk mitigation measures,” the company said. “These include updates to the investigator brochure, the informed consent for patients, and the clinical trial protocol with amended guidance on dose delay, reduction and modification, and prophylactic medications addressing TRAEs.”
Suzhou, China-based MediLink had been testing the HER3-targeting ADC in non-small cell lung cancer and breast cancer since late 2022, building on preclinical evidence that the ADC delivers its cytotoxic payload to tumor cells that express HER3 without causing significant toxicity to healthy tissues.
BioNTech has been involved in the program since October 2023, when it paid $70 million upfront for the rights to the asset beyond China in a deal that had $1 billion in biobucks attached.
BNT326/YL202 was created by MediLink’s solid-tumor-focused TMALIN ADC platform, which BioNTech has tapped for multiple prospects. In May, the German company handed over $25 million upfront for the chance to apply the TMALIN platform to several undisclosed targets.
The two companies aren’t the first to have to amend their ADC dosing to maneuver out of a FDA hold. Mersana Therapeutics suffered FDA holds for two of its ADCs last year that were tied to patient deaths in phase 1 trials. The biotech only saw one of these assets, an immunosynthen STING agonist, return to the clinic permanently once it had confirmed the starting dose would be lowered.