Matthew Krebs, MB, PhD, Talks Rationale for the PALOMA Trial of Subcutaneous Amivantamab in Solid Tumors

Matthew Krebs, MB, PhD spoke about the reasoning for the phase 1 PALOMA trial in patients with solid tumors who received a subcutaneous formulation of amivantamab.

During the American Association for Cancer Research (AACR) 2022 Annual Meeting, Matthew Krebs, MB, PhD, clinical senior lecturer in Experimental Cancer Medicine at the University of Manchester and Honorary Consultant in Medical Oncology at the Christie Hospital in the United Kingdom, spoke to CancerNetwork® about using amivantamab (Rybrevant) subcutaneously in the phase 1 PALOMA trial (NCT04606381) in patients with solid tumor malignancies.

Transcript:

The rationale [for this trial was] in which amivantamab is currently licensed in an intravenous form for patients with EGFR exon 20 mutation[–positive] non–small cell lung carcinoma in the post-platinum setting. The way the intravenous treatment is administered is it splits over 2 days for the first dose because of a risk of infusion-related reaction. It also takes 2 to 4 hours to administer on the first dose; that does come down, but it still takes 1 to 2 hours in general to administer the dosing once patients are established. The subcutaneous administration will potentially shorten the time it takes to administer the drug. Hopefully, it will reduce the risk of infusion-related reactions. It’s just easier to administer to patients and might also avoid the need to have split dosing over that very first dose.

It was designed as a phase 1 trial that is recruiting patients with all solid tumors who might benefit from a drug that targets EGFR or MET, and that could include a range of tumors. There are 2 components to it. First there was a feasibility part where we simply wanted to see whether administration of the intravenous drug given subcutaneously was feasible, and what toxicities that caused. That was either with or without this recombinant human PH20, which can hopefully increase the absorption from the subcutaneous tissues. Then in the second part, we were looking at a higher concentration formulation in a smaller volume [and were determined to see if it] can be administered more quickly and whether that was safe to give, ie toxicities, particularly incidents of infusion-related reactions.

Reference

Krebs MG, Johnson ML, Cho BC, et al. Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: Initial safety and pharmacokinetic results from the PALOMA study. Presented at the American Association for Cancer Research 2022 Annual Meeting. New Orleans, LA. April 8-13, 2022. Abstract CT198 / 23.