The FDA partially halted BioNTech and MediLink Therapeutics’ clinical trial in mid-June after three patients had been reported dead. The phase 1 study was evaluating their ADC candidate BNT326/YL202 in patients with non-small cell lung cancer and breast cancer.
Back in June, BioNTech’s announcement of the FDA hold cited concerns that the drug candidate “may, at higher doses, expose human subjects to unreasonable and significant risk of illness or injuries.”
The FDA requested the drug developers to review clinical and safety data and to provide additional information to the investigators and patients about grade 5 events observed in the study, which refer to death related to or caused by an adverse event.
MediLink Therapeutics, the study sponsor, had observed side effects including neutrophil count decrease (neutropenia) and higher rate of mucositis, particularly in patients who were receiving higher doses of the ADC drug candidate. These are common side effects also seen with established chemotherapies that are known to increase the risk for developing serious infections.
BioNTech and MediLink quickly stopped enrolling patients in the higher dose cohorts and reduced dosing for participants already enrolled at higher dose levels. The partners then implemented further risk mitigation measures, including updates to the investigator brochure and the informed consent for patients, as well as to the clinical trial protocol.
Based on these updates, the FDA has lifted the partial hold on the trial, for which recruitment will be reinitiated. Going forward, patients will receive doses no higher than 3 mg/kg, which have shown to have a manageable safety profile so far.
BNT326/YL202 is an ADC candidate targeting the human epidermal growth factor receptor 3 (HER3). Elevated levels of the HER3 protein have been observed in a wide variety of solid tumors, and is generally associated with a lower survival rate. Preliminary data from the ongoing phase 1 clinical trial, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting earlier this year, showed “encouraging efficacy” in heavily pretreated patients with advanced or metastatic non-small cell lung cancer and breast cancer.
The ADC candidate was originally developed by MediLink Therapeutics, a drug development company focusing on ADCs based in China. In 2023, BioNTech entered a deal potentially worth $1 billion with MediLink to obtain the rights to the drug candidate outside of China.
