GDC-1971 + osimertinib

GDC-1971 + osimertinib is an investigational **combination therapy** under clinical evaluation for cancer, specifically targeting tumors with MAPK pathway dysregulation such as non-small cell lung cancer (NSCLC) and other solid tumors. GDC-1971 (also known as RG-6433 or RLY-1971) is an **allosteric small molecule inhibitor of SHP2** (Src homology region 2-containing protein tyrosine phosphatase 2), a key upstream modulator of RAS/MAPK signaling. By inhibiting SHP2, GDC-1971 disrupts oncogenic signaling and has demonstrated synergy in preclinical models when combined with agents targeting EGFR or KRAS alterations. **Osimertinib** is a third-generation, orally active, irreversible **EGFR tyrosine kinase inhibitor** (TKI) that selectively targets EGFR-sensitizing and T790M resistance mutations. The combination is being studied to overcome primary and acquired resistance to EGFR-targeted therapies by dual blockade of EGFR and SHP2, thereby providing broader or more durable anti-tumor activity in EGFR-mutant or other MAPK pathway–activated cancers[1][2][6][7][3][5].