Autogene Cevumeran Trial Terminated in Resected Colorectal Cancer

BioNTech has decided to terminate the phase 2 BNT122-01 trial (NCT04486378) evaluating autogene cevumeran (BNT122/RO7198457), an investigational individualized mRNA cancer immunotherapy, as adjuvant monotherapy in patients with circulating tumor DNA (ctDNA)–positive, surgically resected high-risk stage II or stage III colorectal cancer (CRC), according to a news release from BioNTech.¹

What led to the decision to terminate the BNT122-01 trial?

The termination follows a new recommendation from the trial’s independent Data Safety Monitoring Board (DSMB), which oversees the study’s safety and integrity. In its most recent review, the DSMB identified a numerical imbalance in OS between the treatment arms in this ctDNA-positive population and concluded that continuing the trial was unlikely to change the efficacy outcome. The board therefore recommended discontinuing treatment for patients still enrolled and terminating the study altogether. No new safety signals associated with autogene cevumeran were identified during the review, and BioNTech has notified investigators and relevant regulatory authorities.

This decision follows an earlier development in October 2025, when the trial crossed the prespecified futility boundary. At that time, the DSMB found the data too immature to draw reliable conclusions about efficacy and determined that follow-up was insufficient to evaluate the trial’s primary end point, so BioNTech continued the trial as planned in the absence of safety concerns.

What was the design of the BNT122-01 trial?

BNT122-01 was a multicenter, open-label, randomized phase 2 trial designed to enroll approximately 327 patients with resected high-risk stage II or stage III CRC, comparing autogene cevumeran with watchful waiting.² Eligible patients were required to have had an R0 surgical resection confirmed by pathology, to be ctDNA positive following resection, and to have at least 5 tumor neoantigens identified from their tumor sample to support individualized manufacturing of autogene cevumeran. The trial’s primary end point was disease-free survival, with OS and safety as secondary objectives.

Notably, the trial tested autogene cevumeran as monotherapy, without a supportive checkpoint inhibitor, to determine whether an individualized mRNA cancer immunotherapy alone could help prevent disease recurrence in this high-risk population.

What is autogene cevumeran and why is colorectal cancer a difficult setting for it?

Autogene cevumeran is an individualized neoantigen-specific immunotherapy formulated as an mRNA lipoplex, designed to stimulate an immune response against as many as 20 patient-specific tumor neoantigens identified from an individual’s own tumor.

“Any decision concerning clinical trials is made with utmost care, keeping patients as our highest priority,” stated Özlem Türeci, MD, co-founder and chief medical officer at BioNTech, in the press release.¹ “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.”

Does this affect other autogene cevumeran trials, including in pancreatic cancer?

The termination of BNT122-01 does not affect the phase 2 IMcode003 trial (NCT05968326), which is evaluating autogene cevumeran in combination with checkpoint inhibition and chemotherapy as adjuvant therapy in resected pancreatic ductal adenocarcinoma. That trial continues as planned. Unlike BNT122-01, IMcode003 tests autogene cevumeran alongside a checkpoint inhibitor rather than as monotherapy.

BioNTech said it will conduct a thorough analysis of the BNT122-01 data to inform patient population selection and the broader clinical development strategy for future investigational mRNA cancer immunotherapies, with results to be shared with the scientific and medical community at an appropriate time.

“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,” Tureci concluded.

References

1. BioNTech provides update on phase 2 clinical trial of autogene cevumeran in resected colorectal cancer. News release. BioNTech SE. August 28, 2026. Accessed August 31, 2026. https://tinyurl.com/47zskenn
2. A phase 2 study of autogene cevumeran vs watchful waiting in resected colorectal cancer. ClinicalTrials.gov identifier: NCT04486378. Updated 2026. Accessed August 31, 2026. https://tinyurl.com/nettbfx2