AndroMETa-Lung-713: A phase 2/3 study of telisotuzumab adizutecan (ABBV-400, Temab-A) vs standard of care (SOC) in patients with epidermal growth factor receptor ( <i>EGFR</i> )–mutated non–small cell lung cancer (NSCLC).

Abstract

TPS8661 Background: Patients with advanced EGFR -mutated NSCLC routinely receive third-generation EGFR TKIs in first-line therapy, such as osimertinib or lazertinib, either as monotherapy or in combination with other agents. Following progression, available options primarily include platinum-doublet chemotherapy or amivantamab + chemotherapy, with country-specific approvals for additional agents including antibody-drug conjugates (ADCs). MET gene amplification and c-Met protein (also known as MET protein) overexpression are established mechanisms of acquired resistance to osimertinib. Temab-A is a c-Met–directed ADC composed of the telisotuzumab antibody linked to a potent topoisomerase 1 inhibitor payload and is designed to selectively target c-Met–expressing tumors. In the first-in-human study (NCT05029882), Temab-A demonstrated manageable safety and encouraging efficacy in heavily pretreated EGFR -mutated NSCLC (confirmed objective response rate [ORR] 63%; median duration of response 9.8 months; median progression-free survival [PFS] 10.9 months) (Camidge. JCO 2025;43: abstract 8512). Methods: AndroMETa-Lung-713 (NCT07155187) is a global, open-label, randomized phase 2/3 study enrolling adults with locally advanced or metastatic non-squamous EGFR -mutated NSCLC after progression on 1 prior third-generation EGFR TKI administered in the adjuvant, locally advanced, or metastatic setting, as monotherapy or in combination with other agents. Key eligibility criteria include ECOG PS 0–1, measurable disease per RECIST v1.1, exon 19 deletion or exon 21 L858R mutation, and provision of tumor tissue for c-Met protein immunohistochemistry. In phase 2, approximately 80 patients will be randomized 1:1 to Temab-A dose 1 or dose 2 IV every 3 weeks (Q3W) to select the recommended phase 3 dose (RP3D) on the basis of safety, efficacy, pharmacokinetics (PK), and available biomarker data. In phase 3, approximately 350 patients will be randomized 1:1 to Temab-A RP3D or investigator’s-choice SOC (platinum-doublet chemotherapy or amivantamab + chemotherapy). Treatment continues until disease progression, intolerable toxicity, or other protocol-defined discontinuation criteria are met. The primary endpoints are ORR in phase 2 and PFS in phase 3, assessed by blinded independent central review. Tumor assessments are performed Q6W for 2 years, then Q12W. Assessment of PK, immunogenicity, and exploratory biomarker analyses, including c-Met protein expression levels and ctDNA dynamics, will be conducted. Clinical trial information: NCT07155187 .