BioNTech has shared an updated look at the data that persuaded it to gamble $200 million on a rival to Bristol Myers Squibb’s Yervoy. The phase 1/2 study linked the anti-CTLA-4 antibody to a 29.6% response rate, offering encouragement to BioNTech and partner OncoC4 as they gear up for a pivotal clinical trial.
Bristol Myers won FDA approval for Yervoy in 2011 but, while the antibody causes durable responses in some cancer patients, it served more to give notice that a new era of immuno-oncology was coming than to lead the revolution itself. Because the antibody causes widespread activation of the immune system, toxicity is a problem and side effects prevent patients from receiving optimal therapeutic doses.
BioNTech identified OncoC4 as a company capable of realizing the potential of CTLA-4, leading a $200 million upfront deal for the exclusive worldwide commercialization rights to ONC-392. OncoC4 designed the therapy to selectively eliminate tumor-infiltrating regulatory T cells without affecting T cell activation in the peripheral T cells. In theory, the approach should improve efficacy and reduce toxicity compared to Yervoy and AstraZeneca’s CTLA-4 drug Imjudo.
OncoC4 has begun to validate that idea across a series of data drops from a phase 1/2 trial that is testing ONC-392 as a monotherapy and in combination with Merck & Co.’s anti-PD-1 antibody Keytruda. The latest data come from a cohort of patients with metastatic, PD-(L)1-resistant non-small cell lung cancer (NSCLC).
In the 27 evaluable patients, OncoC4 and BioNTech saw a 29.6% overall response rate, with one person having a complete response. Ten patients had grade 3 or 4 immune-related adverse events. The 30% adverse event rate compares favorably to the safety results (PDF) from the clinical trials that supported the approval of Yervoy.
Bristol Myers’ NSCLC approval covers the use of Yervoy in combinations. OncoC4 and BioNTech want to show ONC-392 works as a monotherapy. A planned phase 3 clinical trial, which is scheduled to start in the third quarter, will compare the anti-CTLA-4 antibody to docetaxel in NSCLC patients who progressed on anti-PD-1/PD-L1 therapy.