PII-049 - CLINICAL PHARMACOKINETICS OF ABBV-400, A NOVEL C-MET-TARGETING ANTIBODY DRUG CONJUGATE, IN PATIENTS WITH ADVANCED SOLID TUMORS.

C. Biesdorf¹, P. Brunsdon¹, M. Sharma², J. Powderly³, M. Neagu Aristide¹, K. Freise¹, R. Menon⁴, A. Parikh⁵, T. Jennaro¹; ¹AbbVie Inc., North Chicago, IL, US, ²START Midwest, Grand Rapids, MI, USA, ³Carolina BioOncology Institute, Huntersville, NC, USA, ⁴AbbVie Inc.,, North Chicago, IL, USA, ⁵AbbVie Inc..

Background: ABBV-400 is an antibody drug conjugate (ADC) consisting of a c-Met targeting antibody conjugated to a potent inhibitor of topoisomerase 1 (Top1) payload. ABBV-400 has shown encouraging activity following intravenous (IV) infusion every three weeks (Q3W) as monotherapy in patients with advanced solid tumors in an ongoing phase 1 study. Herein, pharmacokinetic (PK) and immunogenicity results from this ongoing study are reported.

Methods: NCT05029882 is an ongoing, Phase 1, first-in-human, proof of concept, open-label, dose escalation, dose expansion study evaluating ABBV-400 in subjects with advanced solid tumors. ABBV-400 is being administered as an IV infusion once every 21 days in 21-day cycles in dose escalation (1.6 –6.0 mg/kg) and expansion (1.6–3.0 mg/kg). Intensive PK samples are being collected on cycles 1 and 3; antidrug antibody (ADA) samples are being collected at regular intervals. PK were characterized for 3 analytes, ABBV-400 conjugate, total antibody, and free payload across the range of doses evaluated in the dose escalation phase. PK analyses were performed using non-compartmental analysis and ADA data was summarized.

Results: Preliminary PK data were available from 94 patients. Following the first dose, conjugate and total antibody exposures appear to increase more than dose proportionally across the evaluated doses. Half-life was approximately 3–6 days for conjugate and total antibody. ABBV-400 conjugate and total antibody concentrations were highly correlated (R2=0.97). Payload exposures appear to be approximately dose proportional across 1.6-6.0mg/kg doses with median time to peak concentration (Tmax) of 24 hours and half-life of approximately 7-11 days. Exposures were similar between Japanese patients (N=21) and non-Japanese patients (N=73) and across tumor types. None of the patients with available data had treatment-emergent ADA.

Conclusion: The clinical PK of ABBV-400 has been characterized, confirming the high-stability of the novel drug linker, and supporting Q3W dosing regimen based on the half-life. The ADC has low immunogenicity potential and was generally safe and well-tolerated. The PK was similar across tumor types and between Japanese vs non-Japanese patients.