AbbVie gets a cMet niche

First, the good news for AbbVie: its cMet-targeting ADC telisotuzumab vedotin has received FDA accelerated approval, making it the first therapy for cMet-overexpressing NSCLC. The bad news is that it will be limited to a niche of cMet-high patients, and carries a warning about interstitial lung disease.

The approval is based on the Luminosity trial, which enrolled a broad cMet-positive population, but produced the best results in those with the highest expression of this protein. While around 25% of advanced, EGFR wild-type, non-squamous NSCLC is said to overexpress cMet, only around half of these patients have high expression, according to AbbVie.

One of AbbVie’s rivals, Mythic, has put the cMet high population much lower, at 10% of overexpressers. Mythic is developing an ADC project that, it hopes, will be effective in cMet-intermediate and perhaps even low expressers.

AbbVie also has a next-generation cMet ADC, telisotuzumab adizutecan, whose most advanced indication is colorectal cancer, but which is also being tested in NSCLC. Phase 1 data on that project in EGFR-mutant NSCLC will feature at this year’s ASCO meeting.

Luminosity

For now, though, the focus is on teliso-V (now branded Emrelis), which got the accelerated nod for previously treated non-squamous NSCLC patients with high cMet overexpression, defined as ≥50% of tumour cells with strong (IHC 3+) staining. cMet status will be determined by Roche’s Ventana MET (SP44) assay, which the FDA also approved.

In the phase 2 Luminosity study, cMet-high patients receiving Emrelis had a 35% ORR; the result was a less impressive 23% among cMet-intermediate patients, explaining why the FDA only approved Emrelis in the former.

This will cut down the potential market for AbbVie, and another reason to be cautious could be toxicity. At last year's ASCO meeting two patient deaths, from interstitial lung disease and respiratory failure, were reported. ILD/pneumonitis occurred in 5% of patients receiving Emrelis, according to the label, which also carries warnings of peripheral neuropathy, ocular surface disorders and infusion-related reactions.

Emrelis employs a tubulin inhibitor payload, so perhaps the next-gen teliso-a, which uses a topoisomerase 1 inhibitor, will be cleaner. While the company is evaluating cMet-overexpressing colorectal cancer in its phase 3 Andrometa-CRC trial, it also sees potential in CRC all comers, and is running the phase 2 M24-311 trial to investigate this.

This year’s ASCO will also see early data with teliso-a in EGFR-mutant NSCLC; if the result is positive it could pit the project against the likes of Johnson & Johnson’s Rybrevant and AstraZeneca’s Tagrisso.

In addition AbbVie has an even earlier-stage cMet-targeting programme: the trispecific NK-cell engager ABBV-303, licensed from Dragonfly Therapeutics, in phase 1.

AbbVie’s cMet-targeting ADCs

Notes: CRC=colorectal cancer; FFB=fluorouracil, folinic acid + Avastin. Source: OncologyPipeline & clinicaltrials.gov.