Mirati Therapeutics and Aadi Bioscience have announced a clinical partnership to assess an adagrasib and nab-sirolimus combination in KRAS G12C -mutated, non-small cell lung cancer (NSCLC) and other solid tumours in a Phase I/II trial.

The single-arm, multi-centre, open-label trial’s main objective is to determine the optimal dose, as well as the recommended Phase II dose for the combination drugs.

It will also evaluate the combination drugs’ safety, tolerability, and efficacy in patients with and without previous exposure to a KRAS G12C inhibitor.

Mirati stated that the Phase I/II trial will build on the preclinical data that demonstrates improved anti-tumour efficacy using the adagrasib and nab-sirolimus combination compared to either drug alone.

An investigational KRASG12C selective inhibitor, adagrasib has a long half-life, extensive tissue distribution, and was well tolerated in the studies.

Mirati Therapeutics president, founder and research and development head Charles Baum said: “Our collaborative preclinical work has demonstrated that combinatorial mTOR and KRAS inhibition addresses key bypass and feedback pathways associated with either drug target, and also results in enhanced efficacy in tumour models harboring KRASG12C mutations. 

“We believe the data from this trial may improve patient outcomes.

“This clinical collaboration is an example of how Mirati is aggressively advancing the study of adagrasib both as a monotherapy and in rational combinations as part of our expanding development portfolio to benefit people living with difficult-to-treat cancers.”

Under the partnership deal, the company will provide funding and operate the Phase I/II study.

Along with Aadi, Mirati will also oversee and share the cost of the trial.