BNT327, now in early-phase trials, is part of a class of drugs that could one day challenge Keytruda’s dominance. BioNTech obtained the candidate when it bought Biotheus last month in an acquisition deal that could reach up to $950 million.
BioNTech on Tuesday revealed Phase Ib/II data for its investigational PD-L1/VEGF bispecific antibody BNT327, touting encouraging response and survival outcomes in patients with locally advanced or metastatic triple-negative breast cancer.
The results, presented at the ongoing 2024 San Antonio Breast Cancer Symposium, showed a confirmed overall response of 73.8% at a median follow-up of 18.1 months, with a 95.2% disease control rate. Patients took a median of 1.9 months to respond to BNT327, and the response then persisted for a median of 11.7 months.
Matured median progression-free survival was 13.5 months in the study’s intention-to-treat population. Median overall survival (OS) had not yet been reached at readout, though the 12-month OS rate was found to be 80.8%. OS analysis had nearly matured at 18 months, yielding a 72.2% rate at this time point.
As for safety, BioNTech documented treatment-related toxicities in all treatment patients, nearly 60% of which were grade 3 and 4 in severity. The most common side effects included neutropenia, leukocytopenia, anemia and proteinuria. Almost a third of patients developed immune-related adverse events, including rashes and hyperthyroidism. None of the patients died due to side effects.
Tuesday’s data come from a Phase Ib/II study, conducted entirely in China, which combined BNT327 with nab-paclitaxel. At the time of analysis, 42 patients had evaluable data, and all had been previously untreated. BNT327 was given at a 20-mg/kg dose every two weeks until unacceptable toxicity or disease progression.
BNT327 belongs to an emerging—and closely watched—class of cancer therapies that target both the PD-1 and VEGF pathways, a treatment approach that some companies are betting could eventually dethrone Keytruda as the cornerstone treatment in cancer.
The buzz around this dual-targeting mechanism started in September, when Akeso and Summit Therapeutics unveiled Phase III data for their PD-1/VEGF bispecific ivonescimab. The companies claimed victory over Keytruda after ivonescimab cut the risk of disease progression or death by 50% in patients with non-small cell lung cancer, as compared with Merck’s blockbuster.
Analysts at the time recommended caution. “Merck has a very large amount of data for pembrolizumab [Keytruda] in multiple tumors that are unlikely to be penetrated anytime soon, even if ivonescimab begins to run trials challenging in these indications,” BMO Capital Markets wrote in a note.
Still, BioNTech is betting on the PD-1/VEGF niche. Last month, it went all-in on BNT327 when it acquired Biotheus—the original developer of the bispecific—for up to $950 million. BMO said in a note at the time that the acquisition was a “good deal” for BioNTech. The analyst firm expects $2 billion in sales for BNT327 by 2032 “based on indications we believe BNTX could develop.”
