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Association details:
| Biomarker: | KRAS G12C |
|---|---|
| Cancer: | Solid Tumor |
| Drug: | batoprotafib (TNO155) (PTPN11 inhibitor) + opnurasib (JDQ443) (KRAS G12C inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
4026 / 5 - JDQ443, a covalent inhibitor of KRASG12C with a novel binding mode, shows broad antitumor activity in KRASG12C preclinical models as a single agent and in combination with inhibitors of SHP2, MEK or CDK4/6
Published date:
03/09/2022
Excerpt:
The JDQ443/TNO155 combination improved single-agent activity across CDX models, with comparable antitumor benefit maintained at QD or BID TNO155 schedules in two of three models (LU99 and KYSE410). Combination with TNO155 allowed a reduced dose of JDQ443 to achieve similar target occupancy and antitumor activity versus JDQ443 alone. JDQ443 demonstrates significant activity against a broad range of KRASG12C solid tumor models, both in vitro and in vivo, that is increased when combined with agents targeting both upstream and downstream components of the RAS signaling pathway. The combination benefit of JDQ443 + TNO155 over JDQ443 alone is maintained at reduced doses for both agents.
