Subcutaneous Delivery of Amivantamab in Patients With Advanced Solid Malignancies: The Phase Ib PALOMA Study.
Publication Title
Clinical lung cancer
Document Type
Article
Publication Date
4-1-2026
Keywords
Humans; Male; Female; Middle Aged; Aged; Adult; Injections, Subcutaneous; Antibodies, Bispecific; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; ErbB Receptors; Aged, 80 and over; Neoplasms; EGFR; Non–small cell lung cancer; Pharmacokinetics; Solid tumors; Subcutaneous amivantamab.; oregon; portland; chiles
Abstract
PURPOSE: Amivantamab is an EGFR-MET bispecific antibody approved as an intravenous formulation for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Intravenous delivery is frequently associated with infusion-related reaction (IRRs), which require adopting slow infusion rates and splitting the first dose over 2 days. The PALOMA study assessed the safety and feasibility of subcutaneous amivantamab administration and identified the formulation and recommended phase II doses (RP2Ds) for multiple dosing schedules.
PATIENTS AND METHODS: PALOMA is a phase Ib dose-escalation study in 158 participants with advanced solid malignancies. Primary objectives included pharmacokinetics, safety, and determining RP2Ds for every-2-week (Q2W), every-3-week (Q3W), and every-4-week (Q4W) administration.
RESULTS: The safety profile of subcutaneous amivantamab was largely consistent with intravenous monotherapy; most common toxicities reflected on-target EGFR/MET inhibition. Subcutaneous amivantamab resulted in meaningfully shorter administration time (≤ 10 minutes vs. 2.3 hours for intravenous beyond cycle 3) and lower incidence and severity of IRRs versus historical intravenous data, which eliminates the need for split-dose administration. Pharmacokinetic analyses and population pharmacokinetic modeling/simulation were used to estimate subcutaneous amivantamab RP2Ds of 1600 mg (2240 mg, ≥ 80 kg), 2400 mg (3360 mg, ≥ 80 kg), and 3520 mg (4640 mg, ≥ 80 kg) for Q2W, Q3W, and Q4W schedules, respectively. The observed efficacy was consistent with intravenous amivantamab monotherapy.
CONCLUSION: Subcutaneous amivantamab administration substantially reduced IRRs, obviating the need for prolonged infusions and 2-day split-dosing at first administration. The identified RP2Ds for subcutaneous amivantamab are implemented in ongoing studies evaluating amivantamab regimens in NSCLC, colorectal cancer, and head and neck squamous cell carcinoma.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pulmonary Medicine
Specialty/Research Institute
Pharmacy
DOI
10.1016/j.cllc.2026.02.001
