Roche, BioNTech post 'low' response rate in cancer vaccine trial

A phase 1b trial of a personalized cancer vaccine in development at Roche and BioNTech has chalked up a “low” response rate. Nine of the 108 evaluable solid tumor patients responded when given the vaccine in combination with Tecentriq, although researchers pointed to immune response results to support continued study in other populations.

Roche’s Genentech paid BioNTech $310 million in upfront and near-term milestones in 2016 to gain access to mRNA-based personalized cancer vaccines. The collaboration gave rise to RO7198457, a drug that targets up to 20 tumor-associated antigens (TAAs) expressed by a patient’s cancer. By giving patients mRNA corresponding to TAAs, Roche and BioNTech hope to rally cytotoxic T-lymphocyte and memory T-cell-dependent immune responses against tumors.

Researchers are using this week’s virtual American Association for Cancer Research event to share an early look at whether RO7198457, also known as BNT122, works as hoped. The results contain plenty of ammunition for anyone who is skeptical about the likelihood of Roche and BioNTech ending the long losing streak of cancer vaccines.

Evaluations of 108 patients who received RO7198457 and checkpoint inhibitor Tecentriq identified nine responses, including one complete response. The figures translate into a response rate of 8%. It is unclear whether those subjects would have responded to Tecentriq given as a monotherapy. A smaller assessment of RO7198457 as a monotherapy linked the cancer vaccine to a 4% response rate. 

Juanita Lopez, Ph.D., consultant medical oncologist at The Royal Marsden and co-author of the RO7198457 abstract, said the “clinical response rate overall was low” in a statement about the trial. Despite that, Lopez sees positives in the results, noting that “we were able to generate tumor-specific immune responses in the majority of evaluable patients.”

An analysis of peripheral blood taken from 49 patients found evidence of neoantigen-specific T cell responses in 77% of samples. Viewed alongside the efficacy data, the analysis suggests RO7198457 reliably elicits specific immune responses that rarely translate into reductions in tumor size.

Lopez thinks the health status of participants at baseline may explain why immune activity is failing to translate into partial and complete responses. Participants in the combination trial had received a median of three prior therapies. Almost 40% of subjects had previously received immunotherapy. It is unclear if any of the nine patients who responded to the combination had previously received an immunotherapy. 

The debate over whether RO7198457 is a dud or a good drug given to the wrong patients will remain inconclusive until data from other populations are available. Roche and BioNTech began gathering such data last year by initiating a phase 2 trial of RO7198457 in combination with Merck’s Keytruda. The trial is randomizing previously untreated advanced melanoma patients to receive Keytruda as a single agent or in combination with RO7198457.

That design positions the trial to clear up questions raised by the Tecentriq combination study about what RO7198457 contributes to checkpoint inhibitor cocktails and whether it works better earlier in the treatment pathway. Lopez said work to assess RO7198457 in post-surgery early-stage non-small cell lung cancer patients is also underway.