BioNTech Ends Phase II Trial of BNT122: The Limits of Personalized mRNA Cancer Therapies

BioNTech ended the BNT122 mRNA therapy trial after the survival data raised a concern

On 28 August, BioNTech announced the termination of BNT122-01, a phase II trial of personalized mRNA immunotherapy given after surgery for colorectal cancer, which includes cancers of the colon and rectum. The mRNA instructs cells to produce protein fragments selected from mutations in an individual patient’s tumor. This is intended to train the immune system to recognize the tumor.

The trial enrolled patients with stage II–III colorectal cancer whose blood tests detected ctDNA, which consists of fragments of tumor DNA. The patients were randomly assigned to receive BNT122 or undergo observation. The trial registry describes observation as standard practice in this setting. Participants in the BNT122 group received the vaccine alone, without a drug that releases some of the restraints on T-cells, the immune cells capable of attacking a tumor.

In October 2025, the trial crossed its prespecified futility boundary. The independent data monitoring committee considered the results too immature to support a reliable conclusion about efficacy. It also found that follow-up was too short to assess the primary endpoint, so the trial continued according to the protocol. At the next review, the committee observed a numerical imbalance in overall survival between the groups and recommended stopping treatment and terminating the trial.

In the phase III trial of another personalized mRNA therapy for melanoma, both groups received pembrolizumab, a drug that releases some of the restraints on T-cells. One group also received intismeran. The combination met its endpoints for recurrence-free survival and distant metastasis-free survival. BNT122-01 addressed a different clinical question: whether a vaccine alone, given after surgery for a different type of cancer, was more effective than observation.

The rationale for BNT122 came from work on a different clinical question. In an early phase I trial in pancreatic cancer, 16 patients received, in sequence after surgery, a drug that releases a restraint on the immune response, a personalized mRNA vaccine, and chemotherapy. The researchers detected a vaccine-induced T-cell response in eight patients. That trial examined whether the three-treatment combination could induce an immune response. BNT122-01 examined a different clinical outcome: whether personalized mRNA therapy alone could help prevent colorectal cancer from returning after surgery.

BioNTech is continuing IMcode003, a phase II trial of the same drug in pancreatic cancer, combined with a drug that releases a restraint on T-cells and with chemotherapy. The same drug is being tested in different cancers, in different treatment regimens, and against different clinical questions.