Phase I study of the antibody-drug conjugate ABBV-321 in patients with non-small cell lung cancer and squamous head and neck cancer with overexpression of the epidermal growth factor receptor.

TPS3649 Background: ABBV-321 (serclutamab talirine) is an epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate that consists of a humanized immunoglobulin G1 anti-EGFR monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer via a maleimidocaproyl-valine-alanine linker. Once bound, ABBV-321 is internalized, the maleimidocaproyl-valine-alanine linker undergoes proteolytic cleavage, and the cytotoxic PBD is released, causing DNA cross-links and cell death. Preclinical studies have shown cytotoxicity in numerous human xenograft and patient (pt)-derived tumor models. This first-in-human trial is assessing the safety, pharmacokinetic (PK), and preliminary antitumor activity of ABBV-321 in pts with advanced solid tumor types likely to exhibit elevated levels of EGFR. Methods: This is a 2-part, multicenter phase 1 study (NCT03234712) of ABBV-321 monotherapy in pts (≥18 years; Eastern Cooperative Oncology Group performance status 0–1) with advanced solid tumors associated with overexpression of EGFR. EGFR overexpression will be determined by centralized testing using an RNA-based assay. Primary objectives of the completed part 1 (dose escalation) were to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of ABBV-321 and assess the PK and toxicity and safety profile; part 2 (dose expansion) will evaluate safety and PK profile at the RP2D in specific cohorts (NSCLC and HNSCC). Secondary objectives include assessment of preliminary antitumor activity. Pts will receive escalating doses of ABBV-321 until the MTD/RP2D is determined. Dose-limiting toxicities will be assessed during the first cycle of dosing. Adverse events (AEs) will be evaluated per National Cancer Institute Common Terminology Criteria for AEs (version 4.03). Blood samples for PK analysis (ABBV-321, total antibody, unconjugated PBD) will be collected at designated time points throughout the study. The multinational trial is active, with the first pt screened on 1 Feb 2018. The dose-escalation phase has been completed; screening and enrollment for the expansion phase of the study in NSCLC and HNSCC is underway. Clinical trial information: NCT03234712 .