The Mainz, Germany-based biopharma, BioNTech, announced on Tuesday that its mRNA cancer immunotherapy failed to meet its first dual primary endpoint.
The clinical trial is testing the efficacy of the investigational drug, BNT113, combined with Merck's cancer drug Keytruda, chemically known as pembrolizumab, in patients with advanced head and neck squamous cell carcinoma (HNSCC) linked to the HPV16 virus.
The combination did not show a statistically significant improvement in progression-free survival (PFS), which measures the time a patient lives without their disease worsening, when compared against treatment with Keytruda monotherapy.
The missed endpoint applies to the Phase III component of the AHEAD-MERIT Phase II/III trial. The independent data monitoring committee recommended that the trial continue to assess overall survival, its second primary endpoint.
BioNTech is evaluating its investigational mRNA cancer immunotherapy drug BNT113 in the AHEAD-MERIT trial. The trial progressed with an initial non-randomized safety run-in followed by a randomized comparison in about 285 patients.
BioNTech’s Phase 2/3 clinical trial recruits patients with human papillomavirus 16 (HPV16)-positive head and neck squamous cell carcinoma.
The study is assessing whether adding BNT113 to pembrolizumab, which is an existing immunotherapy drug, launched by Merck, improves treatment outcomes compared with pembrolizumab alone.
The trial enrolled patients with recurrent or metastatic cancer that could not be removed surgically and whose tumors expressed PD-L1, a protein used to help guide immunotherapy treatment decisions. Approximately 285 patients were included in this study.
The trial had two treatment groups:
Group 1: Received BNT113 alongside pembrolizumab
Group 2: Received pembrolizumab alone
It was an open-label study, meaning patients and investigators knew which treatment was being administered.
Researchers selected two primary endpoints to assess the treatment’s effectiveness:
Progression-free survival (PFS): The length of time patients lived without their cancer worsening or dying from any cause.
Overall survival (OS): The length of time patients lived after entering the study, regardless of whether their cancer progressed.
Note: Primary end point is a treatment outcome that determines whether the trial was successful in showing the efficacy of the investigational drug/treatment.
The trial did not meet its first primary endpoint, as the combination of BNT113 and pembrolizumab did not significantly improve progression-free survival compared with pembrolizumab alone.
A clinical trial investigating the safety, tolerability, and therapeutic effects of investigational drug, BNT113.
BNT113 is administered to the participants in combination with pembrolizumab in this particular BioNTech trial, and its efficacy is compared with that of Merck's pembrolizumab alone in patients with a form of head and neck cancer positive for human papilloma virus 16 and expressing the protein PD‑L1.
Despite the trial failing to achieve one of its dual primary endpoints, statistical analysis done by an independent data monitoring committee suggested the investigators continue with the AHEAD-MERIT trial to assess overall survival.
According to the trial’s predefined statistical plan, an independent data monitoring committee believes that the trial can still achieve a statistically significant improvement in overall survival and could still establish a positive outcome, despite the missed PFS endpoint.
The case highlights an important finding that explains why cancer trials measure both disease progression and survival. A treatment may not significantly delay cancer progression, it might help patients live longer.
‘An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC.’
Open Label: Both the study researchers and trial participants know which treatment each participant is receiving.
For instance, in this trial, they know whether a particular participant is receiving BNT113 with pembrolizumab or pembrolizumab alone.
Controlled: The new treatment is compared with another treatment or a control group to see which is more effective.
Here, researchers compare the combination of BNT113 and pembrolizumab with pembrolizumab alone.
Multi-site: The study is conducted at multiple hospitals, clinics, or research institutes rather than at just one location, allowing researchers to recruit participants from different locations.
Interventional: Researchers actively assign participants to a treatment to study its effects, rather than simply observing the treatments they receive as part of routine care.
2-arm trial: Participants are divided into two groups, or “arms,” that receive different treatments.
In this trial, one group receives BNT113 plus pembrolizumab, while the other receives pembrolizumab alone.
Phase II/III trial: This combines two stages of clinical testing: Phase II and Phase III.
Phase II primarily assesses whether a treatment shows promising effects and gathers safety and drug dosage information.
Phase III evaluates the investigational drug’s effectiveness and safety in a larger study population and compares it with an appropriate control or placebo.
In a Phase II/III programme, the stages may be integrated to evaluate safety and efficacy within a coordinated trial design. The specific design and endpoints depend on the individual study.
(Rh/MF/MSM)