Mirati Therapeutics and Verastem Oncology have entered a non-exclusive clinical partnership agreement for analysing adagrasib (MRTX849) plus VS-6766 in a Phase I/II clinical trial to treat non-small cell lung cancer (NSCLC) patients.

Adagrasib is an oral small-molecule inhibitor of KRASG12C developed by Mirati while Verastem Oncology’s VS-6766 is an RAF/MEK signalling pathway inhibitor.

Adagrasib has potentially demonstrated monotherapy responses in NSCLC, pancreatic cancer, colorectal cancer and various other solid tumours bearing KRASG12C mutations.

According to the deal, the companies will jointly oversee the open-label, multicentre, single-arm trial to develop an option for triple hindering of the RAS signalling pathway.

The primary goal of the trial is to detect the maximum tolerated dosage of the combination treatment and recommended dose for Phase II trial in individuals with KRASG12C-mutant NSCLC.

Furthermore, it will evaluate the safety, tolerability and efficacy of adagrasib plus VS-6766 in subjects who have advanced on receiving a KRASG12C inhibitor.

The trial will expand on data from preclinical research, where the combination treatment offered an improved ERK pathway signalling blockade, leading to an increased anti-tumour efficacy as against treatment with either of the drugs administered alone.

Verastem Oncology CEO Brian Stuglik said: “We continue to see evidence of the differentiated potential of the dual RAF and MEK properties and favourable safety profile of VS-6766 as an ideal combination therapy in treating RAS pathway-driven cancers.

“Specifically, this collaboration will provide data on the potential of VS-6766 with adagrasib to provide deeper and more durable responses in patients with KRASG12C-mutant NSCLC by overcoming downstream resistance mechanisms in the RAS pathway to address unmet needs for NSCLC patients with KRASG12C mutations.”

In October 2019, Mirati announced positive initial data from a Phase I/II trial of its experimental drug, MRTX849, to treat solid tumours expressing KRASG12C mutations.