Amgen packs up in Claudin6

Amgen’s Bite T-cell engager technology hasn't lived up to its hype, and this week it emerged that the company had discontinued another of these projects, targeting Claudin6.

BioNTech has long been the leader in Claudin6, but it hasn’t yet begun a pivotal phase 2 trial with its Car-T contender, BNT211, promised for this year. And now the private player Torl Therapeutics is nipping at its heels, recently saying it would start a pivotal study of its ADC in the second half of 2024.

Others in the pipeline remain further behind, but there have been a couple of new entrants since ApexOnco last carried out this analysis, namely Xencor’s T-cell engager XmAb541, and NBL-028, a bispecific project from NovaRock and China’s CSPC Pharmaceutical. The latter is designed to hit Claudin6 and activate the 4-1BB co-stimulatory pathway, an approach being taken by others including Roche. The Swiss group has a trispecific project, SAIL66, that targets Claudin6, CD3 and 4-1BB.

Meanwhile Amgen’s AMG 794 now looks destined for the scrapheap; its phase 1 clinicaltrials.gov entry notes that development has been discontinued following a “business decision”. This, like other Bites, is a T-cell engager that uses a small construct that retains only some antibody features and is much smaller than a full MAb.

By contrast, another clinical-stage T-cell engager, Xencor’s XmAb541, maintains full-length antibody properties, according to the company. However, that group’s bispecifics haven’t always impressed.

BioNTech is taking a different approach with BNT142, an mRNA project designed to spur a patient’s body to make its own T-cell engagers. A phase 1/2 trial began in 2022, but no clinical results have emerged.

BioNTech vs Torl

Data are available on BNT211, the group’s Claudin6-targeting Car-T, which at last year’s ESMO meeting produced a promising-looking 45% ORR among 38 patients with various solid tumours, mainly germ cell and ovarian cancers; however, high doses were deemed to be toxic.

The company has been looking for the ideal phase 2 dose, which might explain why it’s taken so long to start the planned pivotal trial in testicular germ cell tumours. This is still slated for this year, according to BioNTech’s 2024 ASCO presentation.

In the meantime, BioNTech might get overtaken by Torl BioTherapeutics, which has said it plans to start a pivotal phase 2 study in the second half with its ADC contender, TORL-1-23, in ovarian cancer.

Torl’s project produced a 28% ORR across all doses tested among 25 patients with ovarian, testicular and endometrial cancers, in an update presented at last year’s ASCO.

It would be unwise to give much weight to a cross-trial comparison, given the different cancers involved and the fact that both studies were dose finding. Perhaps phase 2 data will give more clues on whether a Car-T or ADC approach will be preferable.

One thing is clear, however: Amgen is out of the Claudin6 race.

The Claudin6-targeting pipeline

Source: OncologyPipeline.