PII-061 - PHARMACOKINETICS (PK) OF MIRZOTAMAB CLEZUTOCLAX (MIRZO-C) IN PATIENTS WITH RELAPSED AND REFRACTORY SOLID TUMORS: FIRST IN HUMAN STUDY RESULTS

b. Noorani¹, A. Salem², L. He³, D. Rizzo⁴, U. Graab⁵, A. Tolcher⁶, B. A. Carneiro⁷, P. M. LoRusso⁸, R. Menon⁹; ¹AbbVie, Inc., Chicago, Illinois, USA, Chicago, IL, USA, ²AbbVie Inc., ³AbbVie, Inc, Chicago, IL, USA, ⁴AbbVie, Inc., Chicago, IL, USA, ⁵AbbVie Deutschland GmbH & Co, Ludwigshafen, Germany, ⁶Clinical Research, NEXT Oncology, San Antonio, TX, USA, ⁷Legorreta Cancer Center at Brown University, Lifespan Cancer Institute, providence, RI, USA, ⁸Yale University/Yale Cancer Center, New Haven, Connecticut, USA, ⁹AbbVie Inc.,, North Chicago, IL, USA.

Background: Mirzotamab clezutoclax (ABBV-155; Mirzo-C) is a first-in-class antibody-drug conjugate (ADC) consisting of an anti–B7-H3 monoclonal antibody, a solubilizing linker, and a BCL-XL inhibitor payload. Mirzo-C is being tested alone and in combination with taxane in an ongoing Phase I study in patients with relapsed and refractory solid tumors. In this study, we evaluated the pharmacokinetics of Mirzo-C following intravenous administration as monotherapy and in combination with taxane.

Methods: Mirzo-C was administered at doses of 1-18 mg/kg Q3W as monotherapy (part 1 a) and 1-16 mg/kg Q3W in combination with paclitaxel or docetaxel (part 1 b). Serial PK samples for three analytes -- ADC, total antibody, and free BCL-XL inhibitor payload -- were collected at different time points and cycles. Antidrug antibodies (ADAs) and neutralizing antibodies against Mirzo-C were measured in serum samples. Data were analyzed using non-compartmental analysis.

Results: Mirzo-C ADC and free BCL-XL inhibitor payloads exhibit approximately dose-proportional PK across 8-18 mg/kg and 1-18 mg/kg Q3W doses, respectively, with a similar Mirzo-C PK profile between monotherapy and combination therapy cohorts. The harmonic mean terminal phase elimination half-life (t1/2) of Mirzo-C ADC ranged from 2 to 8 days across doses. At steady state, minimal accumulation was observed for the Mirzo-C ADC and total antibody ( < 1.5), while a modest accumulation ( < 2) was seen for the payload. In the ADA analysis, approximately 70% of the subjects showed immunogenicity towards Mirzo-C with no apparent impact on its PK.

Conclusion: These findings from the first-in-human study of Mirzo-C demonstrate that the pharmacokinetics have been thoroughly characterized in the phase 1 study as monotherapy and in combination with taxanes and the PK profile is supportive of Q3W dosing.