BioNTech has decided to terminate it’s Phase II clinical trial evaluating autogene Cevumeran, an investigational individualized mRNA cancer immunotherapy, as an adjuvant monotherapy in patients with circulating tumor DNA-positive, surgically resected Stage II (high risk) or Stage III colorectal cancer.

Autogene cevumeran is being jointly developed by BioNTech and Genentech, a member of the Roche Group, and the decision to terminate the trial was made in consultation with Genentech.¹ The decision comes on the heels of a new recommendation from the independent Data Safety Monitoring Board (DSMB), which is responsible for overseeing the safety and integrity of the trial.¹

The futility boundary of the trial was crossed back in October 2025, and at the time DSMB concluded that the data was not sufficiently mature enough to support reliable conclusions regarding efficacy, and noted that follow-up time was insufficient to evaluate the trial's primary endpoint.¹ In the absence of safety concerns and with no objection from the board, BioNTech decided to continue the trial in accordance with the protocol.¹

What did the DSMB find?

In its most recent review of the available trial data, the DSMB identified a numerical imbalance in overall survival between treatment arms in this specific patient population, noting that further trial continuation was unlikely to change the efficacy outcome.¹ The board followed with a recommendation to discontinue treatment of patients in the trial and terminate it altogether.¹ No new safety signals were identified regarding autogene Cevumeran, and BioNTech informed both investigators and relevant regulatory authorities accordingly.

Why was the trial testing autogene Cevumeran?

The Phase II BNT122-01 trial was designed to assess whether an investigational individualized mRNA cancer immunotherapy, given as monotherapy without supportive checkpoint inhibitor treatment, could help prevent disease recurrence in this high-risk patient population compared with watchful waiting, the current standard of care.¹ Colorectal cancer is a biologically complex disease and an immunologically "cold" tumor type that is historically largely unresponsive to immunotherapy and associated with a high risk of metastatic relapse, marking an area of significant unmet medical need.

"Any decision concerning clinical trials is made with utmost care, keeping patients as our highest priority," said Prof. Özlem Türeci, M.D., co-founder and chief medical officer at BioNTech. "While this outcome is not what we had envisioned for mRNA as a monotherapy in colorectal cancer, it provides scientific insight into the challenges of treating immunotherapy-insensitive tumor types with immune-suppressive microenvironments and will help inform the further development of investigational mRNA cancer immunotherapies. We remain committed to mRNA as a key pillar in our oncology strategy and our novel-novel combination approaches. We are deeply grateful to the patients, families, investigators and site teams whose participation has made this important research possible."

As is standard procedure, BioNTech is expected to conduct a thorough analysis of the trial data aiming to provide insights into patient population selection and inform the clinical development strategy for potential further investigational mRNA cancer immunotherapies.¹ Results of the trial will be shared with the scientific and medical community at an appropriate time.

What does this mean for BioNTech's other autogene Cevumeran trial?

The Phase II clinical trial Imcode003, evaluating autogene cevumeran in combination with checkpoint inhibition and chemotherapy in adjuvant pancreatic ductal adenocarcinoma, is not affected and continues as planned.¹ That trial addresses a need to identify improved post-surgery therapies for people with pancreatic ductal adenocarcinoma, since the majority of patients who have the disease resected and receive current standard-of-care chemotherapy either experience recurrence or die from the disease despite aggressive therapy.²

Imcode003 compares the effects of autogene cevumeran, given in combination with atezolizumab and mFOLFIRINOX, against mFOLFIRINOX alone as post-surgery therapy in people with resected pancreatic ductal adenocarcinoma.²

Sources

1. BioNTech Provides Update on Phase 2 Clinical Trial of Autogene Cevumeran in Resected Colorectal Cancer BioNTech August 28, 2026, https://www.biontech.com/int/en/home/mediaroom/news/statements/2026/08/BioNTech-Provides-Update-on-Phase-2-Clinical-Trial-of-Autogene-Cevumeran-in-Resected-Colorectal-Cancer.html
2. A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC (IMCODE003) National Library of Medicine August 4, 2026, https://clinicaltrials.gov/study/NCT05968326