Telisotuzumab adizutecan (Temab-A) plus osimertinib (osi) as 1L treatment for unresectable/metastatic NSCLC.

TPS8663 Background: Most patients (pts) with EGFR-mutated (Mut) NSCLC and 1L osi treatment will eventually develop resistance. Although 1L combination strategies (osi+chemo or amivantamab+lazertinib) show potential long-term benefits, associated toxicities can impact quality of life. Temab-A, an antibody-drug conjugate with a topoisomerase 1 inhibitor payload, targets c-Met protein. MET gene amplification and c-Met protein expression are associated with poor survival outcomes in NSCLC. A Ph1 study of Temab-A in pts with refractory EGFR Mut NSCLC reported encouraging activity and a manageable safety profile (NCT05029882). Herein, we describe a Ph2/3 study of Temab-A+osi as 1L in pts with previously untreated, locally advanced or metastatic NSCLC harboring common EGFR Mut. Methods: Planned enrollment is ~194 pts in Ph2 and ~500 in Ph3 across ~200 sites in 22 countries. Adults (≥18 years) must have histologically/cytologically confirmed metastatic/locally advanced nonsquamous NSCLC with documented EGFR Mut and measurable disease by RECISTv1.1. Pts with prior EGFR tyrosine kinase inhibitor treatment in the metastatic setting are excluded. During dose escalation (Ph2), pts will receive Temab-A (1.6 or 2.4mg/kg) every 3 weeks (Q3W, 1 cycle) intravenously (IV) + 80mg osi daily. During dose expansion (Ph2), after 1 cycle of osi, pts will be randomized to receive Temab-A (1.6, 2.0, or 2.4mg/kg) Q3W IV + 80mg osi daily, or osi monotherapy, and stratified based on c-Met expression levels and history of CNS involvement. Ph2 primary objectives are safety/tolerability, efficacy as measured by objective response rate of Temab-A+osi, and determination of the recommended Ph3 dose (RP3D). Ph2 primary efficacy endpoint is objective response based on blinded independent central review assessment per RECIST v1.1. In Ph3, randomized pts will receive Temab-A+osi at RP3D or standard of care. Additional details for Ph3 will be confirmed after completion of Ph2. Clinical trial information: NCT05029882 .