BioNTech claims a FixVac win

A big readout with BioNTech’s personalised neoantigen-based immunotherapy might have been delayed, but today the company claimed a victory with one of its so-called FixVac candidates, BNT111.

The project, which uses a fixed combination of four mRNA-encoded, tumour-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE), has apparently prevailed in a phase 2 study in post-PD-(L)1 melanoma: BioNTech said that BNT111 plus Regeneron's Libtayo showed improved ORR versus historical control. 

However, the study included a Libtayo monotherapy arm. When asked why this wasn't used as the comparator, BioNTech replied that the statistical design of the study didn't provide for an interarm comparison, adding: “the monotherapy arms were created as calibrator arms to generate data on the contribution of each component.” The company’s press release noted that ORR in the Libtayo monotherapy arm was “in line” with the historical control of anti-PD-(L)1 or anti-CTLA-4 therapy. 

The German company is also keeping the ORR numbers to itself for now. BioNTech previously said that an ORR of 30% would represent success, but the landscape is changing. Iovance’s tumour-infiltrating lymphocyte (TIL) therapy Amtagvi was recently approved based on a 32% ORR (although this number likely flatters the TIL, as that analysis excluded several patients), while data released last month with Replimune’s oncolytic virus vusolimogene oderparepvec looked slightly better on a cross-trial basis. 

All else being equal, BNT111 and vuso-vec could both have a convenience advantage over Amtagvi: BioNTech and Replimune’s projects are given off the shelf, while Iovance’s is an autologous cell therapy that takes around a month to produce. 

It’s unclear whether BioNTech will be able to file on these results; the spokesperson told ApexOnco that the company, alongside Regeneron, will decide on next steps based on the full data, expected at a medical meeting in 2025.

The spokesperson highlighted the importance of the data as proof of concept for BioNTech's technology and in particular its FixVac approach; the group has two other FixVac programmes, BNT113 and BNT116,

The next big event for BioNTech could be readout from the Imcode-001 study of its Roche-partnered personalised neoantigen project autogene cevumeran in first-line melanoma, expected later this year. The project is being tested in combination with Keytruda, versus Keytruda alone; results had once been due in 2022.

This story has been updated to include comments from BioNTech.

Cross-trial comparison in post-PD-(L)1 melanoma

Source: OncologyPipeline & clinicaltrials.gov.