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Revolution Medicines SHP2 Inhibitor Enters Netherlands Cancer Institute-Sponsored Phase I/IB Trial

NEW YORK – Clinical-stage precision oncology company Revolution Medicines said on Monday that its investigational SHP2 inhibitor RMC-4630 will be used in the Phase I/IB SHERPA trial conducted by the Netherlands Cancer Institute.

The trial, which is expected to start in the second half of 2020, will investigate RMC-4630 in combination with an investigational ERK inhibitor in patients with solid tumors harboring RAS mutations.

The company said it will be especially looking at how pancreatic cancer patients respond to the therapy. The trial is further supported by additional funding from the Pancreatic Cancer Collective.

RMC-4630 is designed to inhibit the activity of SHP2, a cellular protein upstream of RAS receptor tyrosine kinases. RMC-4630 is currently being studied in two early-phase trials sponsored by Sanofi as both a monotherapy and in combination with MEK inhibitor cobimetinib (Genentech's and Exelixis' Cotellic) for patients with RTK, KRAS, BRAF Class 3, or NF1 LOF-mutated solid tumors. In preliminary data reported in the company's SEC filing, the drug has produced partial responses and stable disease in some patients across both trials. The safety profile observed so far has been in line with pre-clinical evaluations. 

Revolution Medicines also announced last November that it entered into an agreement with Amgen to evaluate RMC-4630 in combination with Amgen's KRAS G12C inhibitor AMG 510 in a Phase IB trial enrolling patients with KRAS G12C-mutated solid tumors. Early data showed that the drug combination has exhibited anti-tumor activity. 

According to the SEC filing, Revolution Medicines plans to announce further collaborations in 2020 to explore RMC-4630 with EGFR inhibitor osimertinib (AstraZeneca's Tagrisso) and with a PD-1 inhibitor, such as pembrolizumab (Merck's Keytruda).

Novartis AG and Jacobio Pharmaceuticals currently have active SHP2 inhibitor development programs, while others, such as Merck, Moderna Therapeutics, Boehringer Ingelheim, and Gilead Sciences, are looking to target RAS mutations in cancer.

Revolution Medicines intends to initially seek approval of RMC-4630 and any other product candidates as a therapy for patients who have received one or more prior treatments. The company also stated in their SEC filing that because predictive biomarkers may be used to identify the right patients for their programs and product candidates, they have plans to partner with companies like Foundation Medicine to develop complementary or companion diagnostics.

In mid-February, Redwood, California-based Revolution Medicines went public, raking in $238 million.

A large proportion of the funds will support the development of the company's multiple RAS programs, including completion of IND-enabling studies for one or more development candidates and initiation of a Phase I clinical trial for one development candidate.