Revolution Medicines designed RMC-4630 to inhibit the SHP2 protein, which is required to regulate cell growth.
Amgen’s AMG 510 is an inhibitor of KRAS G12C, an oncogenic RAS mutant involved in the RAS signalling cascade.
Amgen will conduct the Phase Ib study to investigate the safety, tolerability, pharmacokinetics and efficacy of the investigational combination in patients with advanced solid tumours with the KRAS G12C mutation.
The agreement means Revolution Medicines will supply RMC-4630 for the trial.
Both RMC-4630 and AMG 510 are investigational, selective inhibitors of different oncogenic targets in the RAS signalling cascade.
The Phase Ib trial aims to determine if the simultaneous inhibition of the RAS pathway at two nodes would boost the depth or durability of clinical benefits in the patient population.
Revolution Medicines has an exclusive global research, development and commercialisation agreement with Sanofi for the development of RMC-4630 in patients with RAS-dependent cancers.
Revolution Medicines president and CEO Mark Goldsmith said: “This collaboration with Amgen, a clinical pioneer in the field, provides another opportunity to leverage RMC-4630.
“Our development programme for RMC-4630 currently includes an ongoing Phase I monotherapy trial, an ongoing Phase Ib/II study evaluating a combination with cobimetinib, a MEK inhibitor, and a planned Phase Ib trial evaluating a combination with AMG 510, the leading investigational KRAS G12C inhibitor.”
As part of the agreement, Revolution Medicines obtained an upfront payment of $50m from Sanofi. This will be used to reimburse research and development costs associated with the SHP2 programme.
Sanofi gained an exclusive worldwide licence for the commercialisation of any approved SHP2-targeting products worldwide, subject to co-promotion rights for Revolution Medicines in the US.
The partners agreed to equal profit and loss sharing in the US. Revolution Medicines is eligible for royalties on net sales in ex-US markets, along with more than $500m in development and regulatory milestones.