Combination of Investigational SHP2 Inhibitor and Anti-PD-1 Antibody to be Evaluated in Patients with Solid Tumors
REDWOOD CITY, Calif., June 22, 2020 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (NASDAQ:RVMD), a clinical-stage oncology company focused on developing targeted therapies to inhibit frontier cancer targets, today announced dosing of the first patient in a multicenter Phase 1 clinical trial evaluating the combination of RMC-4630 (SAR442720), the company’s investigational SHP2 inhibitor, and pembrolizumab (Keytruda®), an anti-PD-1 antibody. The trial, which is being sponsored and conducted by the company’s collaboration partner Sanofi, is an open-label, safety, preliminary efficacy and pharmacokinetics study in participants with advanced malignancies. This will include patients with non-small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy, and patients with colorectal cancer who have progressed on or after standard of care therapy.
RMC-4630 (SAR442720) is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. Pembrolizumab, a humanized antibody used in cancer immunotherapy, is designed to selectively inhibit the activity of PD-1, a key immune checkpoint that can prevent the immune system from targeting and killing cancer cells. Pembrolizumab is an approved standard of care for the treatment of NSCLC, including lung cancers harboring RAS pathway mutations.
The company’s recently published research in the journal Cancer Research described the anti-tumor effects of a SHP2 inhibitor such as RMC-4630 (SAR442720) through modulation of key elements of the immune system in preclinical cancer models. These findings demonstrated that inhibition of SHP2 may exert therapeutic anti-tumor effects by modulating multiple arms of the immune response to the tumor in addition to reducing oncogenic signaling within tumor cells themselves. Importantly, these data indicate that these two mechanisms may be additive in their anti-tumor impact. Additionally, company findings from the same preclinical study showed that when the SHP2 inhibitor was combined with an immune checkpoint inhibitor (anti-PD-1), deep and durable tumor growth inhibition was observed, with complete tumor regressions and sustained immunological memory in some mice.
“We have previously shown, in a preliminary report, that RMC-4630 (SAR442720) has activity against NSCLC bearing mutant RAS. There is also a compelling collection of data suggesting that the simultaneous inhibition of SHP2 and PD-1 may drive enhanced anti-tumor activity through potentially complementary mechanisms of action,” said Steve Kelsey, M.D., president, research and development at Revolution Medicines. “Overall, this scientific foundation, and the possibility of combining two agents with activity in RAS-driven tumors, serves as a strong rationale for the clinical trial evaluating the combination of RMC-4630 (SAR442720) and pembrolizumab in patients with solid tumors, including NSCLC, and we look forward to the study results.”
“We believe that SHP2’s key roles within both the RAS signaling pathway and the immune response to tumors support the potential for RMC-4630 (SAR442720) to serve as the backbone of targeted therapy combinations for the treatment of various RAS-dependent tumors,” stated Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “With these compelling findings, we are committed to evaluating broadly the combination of RMC-4630 (SAR442720) with inhibitors of other key oncogenic targets within the RAS signaling pathway and with other anti-cancer approaches such as immune checkpoint inhibitors, including anti-PD-1 antibodies.”