Abstract CT198: Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: Initial safety and pharmacokinetic results from the PALOMA study
Authors: Krebs Matthew G. , Johnson Melissa L. , Cho Byoung Chul , Lee Se-Hoon , Kudgus-Lokken Rachel , Zemlickis Donna , Mitselos Anna , Berkay Eileen , Bauml Joshua M. , Knoblauch Roland E. , Hellemans Peter , Minchom Anna 
Published: June 2022

Abstract
Background: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved for patients with advanced EGFR exon 20 insertion non-small cell lung cancer after progression on platinum-based chemotherapy. First-dose intravenous (IV) delivery leads to infusion-related reactions (IRR) among 66% of patients, resulting in dose interruptions and slower infusion restart rates (infusion duration ranges 2-4 hours) and necessitates splitting of the dose over 2 days (Park Ann Oncol 32[suppl_5]:S981). Subcutaneous (SC) administration of amivantamab, which could simplify and accelerate administration, is being investigated in an ongoing phase 1 study (PALOMA; NCT04606381). Preliminary safety (including IRR) and pharmacokinetics (PK) of SC formulations of amivantamab ± recombinant human hyaluronidase (rHuPH20) for enhanced absorption were evaluated.
Methods: PALOMA is an ongoing phase 1 dose escalation study of amivantamab SC in patients with advanced solid tumors who may derive benefit from EGFR or MET-directed therapy. Eligible patients must have progressed after standard-of-care therapy for metastatic disease, be ineligible for, or have declined current standard therapies. The study objectives were to evaluate the feasibility of administration, safety, and PK of a low concentration formulation, 50 mg/mL of amivantamab ± rHuPH20 (Part 1) and a high concentration formulation, 160 mg/mL of amivantamab ± rHuPH20 (Part 2). Patients in Part 1 and Part 2 received the currently approved dosage of amivantamab, 1050 mg (1400 mg for bodyweight ≥80 kg) SC (weekly for the first 4 weeks and every other week thereafter). This study also evaluated administering the full dose of amivantamab on the first day.
Results: The full safety, PK, bioavailability, and receptor occupancy data of patients enrolled in Part 1 (n=16) and Part 2 (n=17) will be presented. Compared to IV administration, initial SC experience demonstrates the co-formulation of high concentration amivantamab with rHuPH20 shortened the needed infusion time to less than 5 minutes, with initial bioavailability of approximately 65% of IV administration. Saturation of soluble free EGFR and MET was achieved after the first SC dose. The incidence of IRRs was 18.2%, with all events of grade 1-2 severity. The full amivantamab SC dose was safely given at first administration to 14 patients, potentially obviating the need for split dosing.
Conclusions: Initial SC amivantamab ± rHuPH20 was well tolerated with improvements in time and ease of administration and associated with a meaningful reduction in IRRs, eliminating the need for split dosing compared with IV administration. Higher SC dose levels and alternative dosing schedules are being explored.
Citation Format: Matthew G. Krebs, Melissa L. Johnson, Byoung Chul Cho, Se-Hoon Lee, Rachel Kudgus-Lokken, Donna Zemlickis, Anna Mitselos, Eileen Berkay, Joshua M. Bauml, Roland E. Knoblauch, Peter Hellemans, Anna Minchom. Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: Initial safety and pharmacokinetic results from the PALOMA study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT198.