Asco 2022 – Merus gets some competition

 First, the good news for Merus: its Her2/Her3-targeting bispecific, zenocutuzumab, looks just as good, if not slightly better, than it did a year ago. And the group is hopeful that data presented at Asco today, in NRG1-fusion driven cancers, will help support a tumour-agnostic filing towards the end of this year or early 2023.

Now for the not so good news: a rival project from Elevation Oncology has produced similar overall response rates, albeit in a small number of patients so far. In a tiny niche like NRG1 fusions, competition could be a big deal.

Elevation will present early results on its project, the Her3-targeting MAb seribantumab, at Asco on Tuesday, but it has already detailed the full dataset via press release, a spokesperson told Evaluate Vantage.

Cross-trial comparison of zenocutuzumab & seribantumab
	Zenocutuzumab: Enrgy & Early Access Program			Seribantumab: Crestone
	Asco 2021 presentation	Asco 2022 presentation		Asco 2022 presentation
Cutoff	Apr 13, 2021	April 12, 2022		April 18, 2022
ORR – overall	31% (14/45)*	34% (27/79)		33% (4/12)**
ORR – pancreatic cancer	42% (5/12)	42% (8/19)		0% (0/1)
ORR – NSCLC	29% (7/24)*	35% (16/46)		36% (4/11)**
ORR – other solid tumours	22% (2/9)	18% (3/17)		N/A
*Included one PR confirmed after cutoff date; **Includes 2 CRs. Source: Asco & company releases.

The seribantumab results call into question something that Merus has long maintained: that its dual approach, docking onto Her2 and then blocking Her3, could be more potent than monoclonal antibodies (Asco 2021 – Merus’s slight improvement might not win over investors, June 4, 2021).

However, Merus’s chief executive, Bill Lundberg, maintained this claim when Evaluate Vantage spoke to him on the sidelines of Asco. “We think we have the potential not only to be first in class, but potentially best in class in this setting.”

He noted that patients in Merus’s Enrgy trial and early-access programme received a median of two prior therapies, compared with a median of one in Elevation’s Crestone trial. This raises the possibility that patients in Crestone were less sick, which could have flattered seribantumab’s performance.

And Mr Lundberg added: “We're a couple of years ahead.”

Small market

In NRG1 fusion cancers this head start could make a difference. Merus currently estimates that 0.5-1.5% of pancreatic cancer and 0.3-3% of lung cancer patients have NRG1 fusions, but Mr Lundberg noted these numbers are based partly on epidemiologic studies using old sequencing methods.

“We think the numbers could increase over time with better diagnosis,” he said. “But it's not going to dramatically be tenfold higher. We think it’s several thousand patients per year in the US.”

For now, Merus is not saying how many patients it will need for a US filing, only that it has reached agreement on this with the FDA. “And we believe we'll have sufficient patients with sufficient clinical follow-up around the middle of this year.”

It is not clear yet whether this could support an accelerated or full approval; Mr Lundberg said this would be up to the FDA. The group is currently considering whether to go it alone or sell zenocutuzumab via a partner, assuming it does get the nod.

Competition

Still, Mr Lundberg admitted that the anti-Her3 space is getting crowded. As well as Elevation, Hummingbird Bioscience’s HMBD-001 recently went into the clinic in Her3-positive solid tumours, including NRG1 fusion-driven cancers.

Meanwhile, Aveo Oncology still has hopes of reviving AV-203, despite it being ditched by two partners: Biogen in 2014 and China’s Canbridge in 2021. Aveo is also developing a Her3-targeting antibody radio-conjugate alongside Actinium.

GSK’s GSK2849330 has also produced intriguing results in NRG1 fusion cancers, but is not currently listed on the company’s pipeline.

And Daiichi’s Her3-targeting antibody-drug conjugate patritumab deruxtecan produced encouraging results in breast and lung cancers at Asco, but the company does not appear to be focusing on NRG1 fusions.

Merus will need to keep its first-mover advantage if it wants to make the most of this niche.

Her3-targeting projects with potential in NRG1 fusion cancers
Project	Company	Description	Details
Zenocutuzumab	Merus	Anti-Her2/Her3 bispecific	Filing due late 2022/early 2023 based on ph1/2 Enrgy & EAP
Seribantumab	Elevation Oncology	Anti-Her3 MAb	Early data from ph1/2 Crestone at Asco 2022; trial could be basis for AA
HMBD-001	Hummingbird Bioscience	Anti-Her3 MAb	First pt dosed in ph1/2* in Dec 2021
GSK2849330	GSK	Anti-Her3 MAb	Ph1 completed 2017, one of two NRG1 fusion pts had partial response
AV-203	Aveo Oncology	Anti-Her3 MAb	Ph1 completed 2014, one of two NRG1 fusion pts had a partial response
*Investigator-sponsored, study enrols pts with Her3-expressing tumours, including NRG1 fusion pts. AA=Accelerated approval; EAP=Early access programme. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/events/conferences/asco-2022-merus-gets-some-competition