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BridgeBio, Navire Dose First Patient in SHP2 Inhibitor Trial for Certain Solid Tumors

NEW YORK – BridgeBio Pharma and its subsidiary Navire Pharma on Friday announced that the first patient has received their investigational SHP2 inhibitor, BBP-398, within a Phase I study evaluating the treatment in solid tumors harboring MAPK signaling pathway genetic mutations.

The trial, which is expected to enroll roughly 60 patients, is divided into two parts. The first part will evaluate the agent's safety and maximum tolerated dose, while the second part will evaluate the agent's preliminary anti-tumor activity — as defined by objective response rates and duration of response —across four cohorts of patients stratified on the basis of their specific cancer types and molecular alterations.

These cohorts include patients with non-small cell lung cancer harboring KRAS G12C mutations; patients with KRAS G12C-mutated lung cancers other than NSCLC; patients with EGFR-mutated NSCLC; and patients with other solid tumor types harboring MAPK signaling pathway genetic mutations excluding BRAF V600X. All patients enrolled must have advanced cancers and be out of standard therapy options. The EGFR-mutated NSCLC cohort will include patients who have previously received anti-EGFR tyrosine kinase inhibitors.

BBP-398, which was originally developed at the MD Anderson Cancer Center, is designed to inhibit the conserved protein tyrosine phosphatase SHP2, which plays a regulatory role in cancer cell growth and division by way of the downstream ERK, RAS, and MAPK pathways.  

"SHP2 inhibitors have the potential to be effective additions to the therapeutic arsenal for difficult-to-treat cancers by overcoming multiple mechanisms that tumors use to evade treatments," BridgeBio CSO Eli Wallace said in a statement. "This study is a critical step in understanding the potential that BBP-398 has for patients with tumors driven by RAS or other MAPK-pathway activating mutations and informing our future clinical development activities."

SHP2 has been a target of interest for other drugmakers, too. In June, for example, Revolution Medicines began dosing patients with KRAS G12C-mutated solid tumors in a clinical trial evaluating its own SHP2 inhibitor in combination with Amgen's KRAS G12C inhibitor AMG510.