Incyte has entered a clinical trial partnership and supply agreement with Mirati Therapeutics to assess the combination of INCB99280 and adagrasib (MRTX849) for KRASG12C-mutated solid tumours.

INCB99280 is Incyte’s small molecule oral inhibitor of PD-L1.

As per the terms of the deal, Incyte will commence and sponsor a Phase I/Ib clinical trial of INCB99280 plus adagrasib for treating patients with KRASG12C-mutated solid tumours. 

For the trial, Mirati will supply adagrasib to Incyte.

INCB099280 showed favourable clinical activity and safety in solid tumour patients. 

It will be assessed in Phase II trials as a single agent, and along with other antitumour agents.

An investigational, oral small-molecule KRASG12C inhibitor, adagrasib is tailored to support target inhibition.

Because the KRASG12C protein regenerates every 24-48 hours, such inhibition could be vital for treating KRASG12C-mutated cancers.

According to the studies of adagrasib, the drug showed to have an extended half-life and wide tissue distribution, and is well tolerated. 

Adagrasib also demonstrated single-agent responses and central nervous system penetrance in trials in non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer, and other solid tumours with KRASG12C mutations. 

Incyte Clinical Development Hematology and Oncology group vice-president Lance Leopold said: “Incyte’s small molecule, oral PD-L1 programme has shown promising safety and efficacy in early studies- INCB99280’s shorter half-life may result in improved management of immune mediated adverse events and better clinical outcomes. 

“We are pleased to collaborate with Mirati to conduct the first clinical trial of INCB99280 plus adagrasib, two orally-bioavailable molecules, in patients with KRASG12C-mutated solid tumours.”

In October this year, Mirati and Aadi Bioscience entered a clinical collaboration to evaluate an adagrasib and nab-sirolimus combination in KRASG12C-mutated NSCLC and other solid tumours in a Phase I/II trial.