One of BioNTech’s prospective cancer vaccines has failed to show benefit in one of its dual primary endpoints in a Phase II/III trial in patients with head and neck squamous cell carcinoma (HNSCC).
In the AHEAD-MERIT study (NCT04534205), the combination arm of BioNTech’s mRNA cancer immunotherapy BNT113 (tenumomeran/raplemomeran) plus MSD’s Keytruda (pembrolizumab) did not demonstrate a statistically significant improvement in progression-free survival (PFS) versus Keytruda alone, meaning the trial missed one of its dual primary endpoints.
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Despite the PFS miss, the Independent Data Monitoring Committee (IDMC) has recommended that the clinical trial continue as planned to evaluate the second primary endpoint of overall survival (OS).
Under the trial’s pre-specified statistical design, a statistically significant improvement in OS would establish a positive trial outcome, even if the PFS dual primary endpoint was not met. Despite this second chance, BioNTech’s shareholders appear to have concerns, with the company’s stock having dropped 3.63% at market open on 13 October ($92.36), from a 12 October close of $95.84.
Professor Özlem Türeci, co-founder and CMO at BioNTech, said: “The potential of mRNA cancer immunotherapies in combination regimens lies in their ability to induce immune responses that may translate into durable clinical benefit and, ultimately, prolonged survival of patients.
“While the PFS result was not statistically significant at this first analysis, the data support continued evaluation of BNT113 plus pembrolizumab in this trial and show that it is engaging its intended therapeutic mechanism. As immune-mediated anti-tumour effects build and deepen over time, the analysis of the second dual primary endpoint, overall survival, will be critical to fully assess the potential of this approach to deliver durable benefit for patients with HPV-driven head and neck cancer.”
The clinical trial is evaluating the mRNA-based cancer vaccine and immune checkpoint inhibitor (ICI) combination in patients with unresectable recurrent or metastatic human papillomavirus 16-positive (HPV16+) HNSCC expressing PD-L1.
Approximately one third of HNSCC cases are associated with HPV infection, with the majority linked to HPV16. Despite the distinct characteristics of HPV-positive tumours, there are currently no HPV-targeted treatments approved. BioNTech has been granted US Food and Drug Administration (FDA) Fast Track designation for BNT113 in HPV16+ HNSCC.
This is not the only cancer vaccine in BioNTech’s portfolio. It is currently running mid-stage trials of autogene cevumeran, which is a personalised vaccine, in partnership with Genentech, while BNT113 is an off-the-shelf vaccine. One of the studies, in bowel cancer, was terminated after it was deemed unlikely to show benefit. Another study, in pancreatic cancer, is ongoing.
In contrast to the recent setbacks faced by BioNTech, the partnership between MSD and Moderna has yielded a historic breakthrough in the mRNA cancer immunotherapy space.
Central to this is the flagship candidate, intismeran autogene, which achieved the first-ever successful Phase III trial readout for an individualised mRNA cancer therapy. In the INTerpath-001 trial, intismeran autogene was investigated in combination with MSD’s Keytruda versus Keytruda alone in over 1,100 patients with high-risk (Stage IIB-IV) resected melanoma. The combination therapy demonstrated a statistically significant and clinically meaningful improvement in Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS).
According to GlobalData, the drug is likely to achieve blockbuster status in 2031. GlobalData is the parent company of Clinical Trials Arena.
This readout caused Moderna’s stock price to skyrocket and has been described by key opinion leaders (KOL’s) as a true turning point for these kinds of therapies. Detailed data from this study are expected during the European Society of Clinical Oncology meeting, being held in Madrid, Spain, from 23 to 27 October.
