Natasha Leighl, MD, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, discussed results from phase 3 PALOMA-3 trial which compared subcutaneous and intravenous amivantamab plus lazertinib administration among patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). 

Results demonstrated that subcutaneous administration was superior in terms of pharmacokinetics and objective response in this patient population. 

Transcript: 

Natasha Leighl, MD, from the Princess Margaret Cancer Center in Toronto, Canada. Here at ASCO 2024, we presented the results of the PALOMA-3 study where we compared the pharmacokinetics and efficacy results of subcutaneous amivantamab plus intravenous (IV) amivantamab both in combination with lazertinib in patients with EGFR-mutant advanced lung cancer that had previously received osimertinib and chemotherapy.

The reason for this study was that amivantamab is currently a very active drug in patients with EGFR-mutant lung cancer and is approved as an intravenous formulation but the IV formulation takes about 4 hours for the first dose, and requires split dosing for the very first dose of the treatment, and also has infusion-related reaction rate of 67%. We developed the subcutaneous formulation with the aim of decreasing patient administration time, and what we found was that in an initial dose finding study, PALOMA, patients had a very low rate of infusion-related reactions compared to the IV formulation.

In PALOMA-3, we compared the outcomes including pharmacokinetics in patients. We randomized 418 patients, characteristics were well balanced across the arms, and we did demonstrate non-inferior pharmacokinetic profiles with similar exposures between subcutaneous and IV amivantamab. We also showed similar efficacy, approximately the same response rate, similar PFS (slightly longer with subcutaneous amivantamab but not statistically significant), and to our surprise we found that overall survival significantly favored the subcutaneous amivantamab plus lazertinib arm ( hazard ratio 0.62; P -value was .02). Toxicities were similar overall, mostly EGFR and MET-related, grade 1/2 and similar to what we've seen in other amivantamab and lazertinib studies however, the incidence of infusion-related reactions was 5 fold less, 13% in the subcutaneous arm compared to 66% in the IV arm, and also we saw that venous thromboembolic events were less frequent in patients receiving subcutaneous amivantamab. 

Now this was the first study to effectively look at the use of prophylactic anticoagulation with amivantamab and lazertinib after the signals of increased VTE in the MARIPOSA study, and what we found was that prophylaxis significantly decreases the risk of VTE down to 10% in those who receive prophylaxis versus 21% in those who didn't, we recommended prophylaxis in all patients but only about 80% ended up taking it out. The other great finding from the study was that we were able to give subcutaneous amivantamab in 1 syringe in less than 5 minutes compared to 5 hours for the first day of the first dose of amivantamab, again requiring 2 days for that initial dose, and then 2 hours on subsequent IV infusions. Eighty-five percent of patients said that subcutaneous amivantamab administration was convenient or very convenient significantly more than in the IV arm. 

In PALOMA-3, we demonstrated non-inferior pharmacokinetics, non-inferior to in some cases potentially better efficacy, as well as better safety with fewer IRRs and fewer VTE events, as well as greater patient convenience and also provider convenience compared to the IV formulation.

Source: 

Leighl NB, Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract LBA8505