Mirati and Sanofi will assess the combination of adagrasib and SAR442720 in a Phase I/II study in patients with previously treated non-small-cell lung cancer who express KRASG12C mutations.
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Fresh off the presentation of positive data showing that adagrasib, a KRASG12C inhibitor benefited colorectal and lung cancer patients, Mirati Therapeutics forged an agreement with Sanofi to combine the drug with that company’s SHP2 inhibitor SAR442720 in lung cancer.
San Diego-based Mirati Therapeutics and Sanofi will assess the combination of adagrasib and SAR442720 in a Phase I/II study in patients with previously-treated non-small cell lung cancer (NSCLC) who express KRASG12C mutations. Charles M. Baum, president, founder and head of research and development at Mirati, said a “strong scientific rationale” supports the combination of a KRASG12C inhibitor with an SHP2 inhibitor. He also acknowledged that the combination could optimize clinical outcomes for patients who have KRASG12C-dependent tumors.
SHP2 is upstream of KRAS, mediates cellular signaling through the RAS/MAP kinase pathway, and is often overactive in different types of cancer. Inhibition of both has corresponding action mechanisms and has shown additive anti-tumor activity in pre-clinical models.
“Mirati is aggressively advancing a broad adagrasib development program, which includes pursuing novel combination approaches including through this collaboration with Sanofi,” Baum said in a statement.
Under the terms of the agreement, Sanofi will be responsible for the Phase I/II study. Financial terms of the collaboration were not disclosed. SAR442720, formerly known as RMC-4630, came to Sanofi through a partnership with Revolution Medicines.
For Mirati, the Sanofi deal comes on the heels of a Phase I/II data presentation at the European Society of Medical Oncology meeting that showed adagrasib as a monotherapy and in combination with cetuximab demonstrated significant clinical activity and broad disease control in patients with heavily pretreated colorectal cancer who exhibit the KRASG12C mutation, as well as non-small cell lung cancer.
The KRYSAL-1 study showed that patients who received adagrasib saw a disease control rate of 87%. In all enrolled patients, the median progression free survival was 5.6 months, the company said in its presentation last month.
Mirati is also developing sitravatinib, an investigational spectrum-selective inhibitor of receptor tyrosine kinases, as well as MRTX1133, an investigational KRASG12D inhibitor, MRTX1719, an investigational PRMT5 inhibitor, and other oncology discovery programs.
In addition to the adagrasib news, Mirati also tapped David Meek as its new chief executive officer last month. Meek previously served as president and CEO of FerGene. He also held the CEO role at IPSEN, where he guided the company through expanding its oncology portfolio.
