Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: PALOMA, an open-label, multicenter, dose escalation phase 1b study.
Authors: Krebs Matthew , Johnson Melissa Lynne , Cho Byoung Chul , Park Keunchil , Haddish-Berhane Nahor , Zemlickis Donna , Mitselos Anna , Meacle Francis , Knoblauch Roland Elmar , Hellemans Peter , Minchom Anna Rachel 
Published: June 2021

TPS3150 Background: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody with immune cell-directing activity, targets activating/resistance EGFR mutations and MET mutations/amplifications. Amivantamab has demonstrated antitumor activity in patients (pts) with EGFR-mutant NSCLC and also in pts with EGFR tyrosine kinase inhibitor-resistant disease. The recommended phase 2 dose (RP2D) is 1050 mg (1400 mg, ≥80 kg) administered as intravenous (IV) infusions weekly (QW) for the first 28-day cycle and every other week (Q2W) thereafter. A subcutaneous (SC) formulation of amivantamab has the potential to reduce pt and physician burden by reducing administration time. The safety and pharmacokinetics (PK) of amivantamab administered SC ± recombinant human hyaluronidase (rHuPH20) will be evaluated. Methods: PALOMA is an ongoing phase 1b dose escalation study of amivantamab SC in pts with advanced solid tumors that may derive benefit from EGFR or MET-directed therapy (NCT04606381). Pts must have progressed on standard of care therapy for metastatic disease, be ineligible for, or have refused current standard therapies. The primary endpoints are trough concentration at the end of QW dosing and safety of SC administration. The objective of part 1 is to evaluate the feasibility, safety, and PK of SC administration of a low concentration (50 mg/mL) formulation of amivantamab alone (Ami-LC) or admixed with rHuPH20 (Ami-LC-MD). Approximately 8 pts will be enrolled to receive either 1050/1400 mg amivantamab SC using Ami-LC-MD (Cohort 1a) or Ami-LC (Cohort 1b) QW in cycle 1 and Q2W thereafter. The objective of part 2 is to evaluate the safety and PK of SC administration of a high concentration (160 mg/mL) formulation of amivantamab alone (Ami-HC) or with rHuPH20 (Ami-HC-CF) and to determine a dose, schedule, and formulation for SC administration that achieves similar exposure as observed at the RP2D of amivantamab IV, with acceptable safety. Pts enrolled in part 2 will initially receive 1050/1400 mg amivantamab SC using Ami-HC-CF in Cohort 2a or Ami-HC in Cohort 2b. ≤10 pts may be enrolled in either cohort. Additional cohorts of ≤10 pts may be enrolled to support dose, schedule, and formulation selection as guided by safety and PK observations in earlier cohorts. To mitigate infusion related reactions (IRR), medication with steroid, paracetamol, and antihistamine will be given pre-infusion and as clinically indicated post-infusion. Safety assessments include monitoring adverse events, laboratory abnormalities, vital signs, IRR, and injection site reactions. Blood samples will be collected to assess PK, pharmacodynamics, and immunogenicity. A Study Evaluation Team composed of investigators and sponsor representatives will review safety and PK data to make decisions about dose escalation and cohort expansion throughout the conduct of the study. Clinical trial information: NCT04606381.