The PALOMA trial is an ongoing phase 1b dose escalation study evaluating subcutaneous amivantamab plus rHuPH20 in patients with advanced solid tumors who may benefit from EGFR- or MET-targeted therapy.

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Anna Minchom, MBBCh, MRCP, MD(Res), The Royal Marsden Hospital, Sutton, United Kingdom, presented updated safety results from the PALOMA trial and the identified recommended phase 2 dose for subcutaneous biweekly administration of amivantamab. 

Transcript: 

My name is Dr. Anna Minchom. I'm a medical oncologist from the UK from the Royal Marsden Hospital.

At ASCO this year, I'm presenting results from the PALOMA Study. The PALOMA Study is a phase 1 study of a subcutaneous preparation of amivantamab. Now, amivantamab is usually administered intravenously. This drug is an [epidermal growth factor receptor] (EGFR)-MET bispecific antibody but is licensed in exon-20 insertion on small cell lung cancer, and is being investigated in other types of EGFR lung cancer. With the intravenous preparation, there are high rates of infusion-related reactions, which necessitate a prolonged infusion time, observation period, and split dosing on cycle 1, split over day 1 and day 2.

The subcutaneous preparation hopes to overcome the infusion-related reactions. This phase 1 study had a dose escalation component. The drug was administered periumbilically, so under the skin and the abdominal tissues. Interestingly, the rates of infusion reactions were very low, 16%, and only grade 1 and grade 2, so no grade 3 or grade 4 infusion-related reactions. The drug was also feasible, with low rates of mild injection site reactions only.

This trial was very heavy in pharmacokinetic analysis to determine the equivalent dose of the intravenous preparation, and the dose that was determined was determined both for a 2-weekly administration and for a 3-weekly administration. The doses are dose-banded, with a higher dose for those patients over 80 kilograms. [For] the 2-weekly regime, the recommended phase 2 dose of the subcutaneous preparation is 1600 milligrams for those under 80 kilograms, and 2240 [milligrams] for those over 80 kilograms. For the 3-weekly dosing, it's 2400 milligrams for those under 80 kilograms, and 3360 milligrams for those over 80 kilograms. This subcutaneous preparation is going to be used in ongoing studies, such as a PALOMA-2 and a PALOMA-3 study.
 

Source:

Minchom AR, Krebs MG, Cho BC, et al. Subcutaneous amivantamab (ami) in patients (pts) with advanced solid malignancies: The PALOMA study—Updated safety and identification of the recommended phase 2 dose. Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 9126