AbbVie has Met phase 3, again

AbbVie already has a cMet-targeting ADC filed with the FDA, and another could follow in the not too distant future. The company is planning to take its next-generation project, telisotuzumab adizutecan, into phase 3 in its lead indication, colorectal cancer, according to a new listing on the clinicaltrials.gov registry.

The trial will test teliso-A monotherapy in patients with refractory colorectal cancer and cMet overexpression – which makes sense given that a cMet-high subgroup performed best in the CRC cohort of a phase 1 basket study.

The control group will receive Lonsurf plus Avastin, a reasonable comparator in late-line disease. The clinicaltrials.gov entry makes no mention of microsatellite status.

Curiously, though, AbbVie has begun phase 3 before readout of a phase 2 CRC trial testing teliso-A alongside fluorouracil, folinic acid and Avastin in previously treated microsatellite-stable patients.

Trials in other uses are also in the works, with an Israeli phase 2 in gastric cancers yet to begin recruiting, and a mid-stage study in NSCLC planned, AbbVie said during its second-quarter earnings call in July.

And more indications could follow, if data from another basket trial look promising.

Teliso-A vs teliso-V

AbbVie recently filed its first-generation cMet ADC, telisotuzumab vedotin, for accelerated approval in EGFR wild type, cMet overexpressing, non-squamous NSCLC. The company estimates that around a quarter of advanced EGFR wild-type NSCLC patients overexpress cMet; however, the most promising response rates with teliso-V have been seen in a smaller subset of patients with high expression levels.

And at this year’s ASCO meeting two deaths were reported as possibly related to teliso-V, caused by interstitial lung disease and respiratory failure.

The FDA will have to weigh up the project’s risks and benefits in a population with no specifically approved therapies. A confirmatory trial, Telimet NSCLC-01, is under way.

Teliso-A, which until recently went under the lab code ABBV-400, could have advantages over teliso-V: the former uses a topoisomerase 1 inhibitor payload, while the latter employs the tubulin inhibitor monomethyl auristatin E.

Certain cMet-targeting projects are already approved, such as Johnson & Johnson's anti-EGFR x cMet MAb Rybrevant, but AbbVie is ahead in the cMet ADC space. Its mid-stage rivals include RemeGen, with RC108, and Regeneron, with the biparatopic project davutamig.

Notable trials with telisotuzumab adizutecan

Notes: BC=breast cancer; BTC=biliary tract cancer; CRC=colorectal cancer; FFB=fluorouracil, folinic acid + bevacizumab (Avastin); ESCC=esophageal squamous cell carcinoma; GEA=gastroesophageal adenocarcinoma; HCC=hepatocellular carcinoma; HNSCC=head & neck squamous cell carcinoma; NSCLC=non-small cell lung cancer; PDAC=pancreatic ductal adenocarcinoma. Source: OncologyPipeline.