Revealed: Merck’s double bet on TROP2

Just over two years after Merck & Co licensed the anti-TROP2 antibody-drug conjugate sacituzumab tirumotecan from Kelun, the US group advanced its own identically acting ADC into clinical development. This unusual fact has just emerged from an obscure Israeli clinical trial registry that discloses for the first time the mechanism of action of the Merck project MK-6837.

It’s notable that since MK-6837 entered its phase 1 study in July 2024 secrecy has surrounded its mechanism of action. The fact this molecule has turned out to be an anti-TROP2 ADC explains such secrecy: Merck working simultaneously on its own version of saci-T could call into question the importance of the Kelun deal, which is seen as a key pillar of its ADC strategy.

It’s also somewhat unusual that Merck is even allowed to develop an in-house asset that would theoretically compete against saci-T. However, the details of the 2022 Kelun deal are confidential, so it must be assumed that the tie-up didn’t preclude the US company from working independently on similarly acting projects.

Merck didn’t respond to a request from ApexOnco to confirm the mechanism of MK-6837 and explain its reasoning for developing two anti-TROP2 ADCs simultaneously.

Importance

Some might dismiss the original 2022 licensing deal as small fry for Merck, given that it was worth just $47m up front. But the importance of saci-T can’t be denied, given that the molecule is now in 17 Merck-sponsored pivotal studies seeking to enrol over 15,000 patients and spanning numerous tumour types.

Neither can the importance of Kelun to Merck be underestimated. The companies’ collaboration has been expanded several times since the saci-T transaction, and now includes several other ADCs. And, together with a monster 2023 tie-up with Daiichi Sankyo, Kelun serves as a key source of Merck’s ADC expertise.

So why is Merck developing a me-too TROP2-directed ADC? Crucially, nothing is known about the precise structure of MK-6837, so this molecule’s similarities and differences versus saci-T remain unclear. They might use the same antibody – sacituzumab has little patent protection – but probably employ a different payload.

One possibility is that different characteristics of the two will make MK-6837 applicable to different settings than saci-T, or perhaps Merck simply wants to have a back-up plan for saci-T. A sinister read might be that Merck wants to circumvent some onerous terms of the Kelun deal, or that the US group is somehow cooling on saci-T, though of course there’s no evidence for this.

Confidential

It seems clear that Merck wanted to keep the mechanism of MK-6837 confidential, given that the molecule’s main clinicaltrials.gov listing reveals nothing about it. 

But its cover has been blown by a little-known registry of Israeli clinical studies, whose listing of Merck’s phase 1 study states: “MK-6837 is a novel antibody-drug conjugate that binds to the tumour-associated antigen TROP2.”

This isn't the first minor registry to give away more vital detail than clinicaltrials.gov itself. The EU trial registry has revealed clinical holds, for instance, while a website listing studies at Florida cancer centres recently disclosed JNJ-95437446 to be a challenger to J&J’s own Rybrevant.

Those now poring over over the Israeli clinical trials registry will note that it gives away the mechanism of another project, stating that AbbVie’s ABBV-324 is an anti-GPC3 ADC. That asset entered phase 1 last year, and its clinicaltrials.gov listing gave no clue as to its mechanism.