Leighl Covers PALOMA-3 Trial of SC Amivantamab in NSCLC
Natasha Leighl, MD, MMSc, BSc, discussed key findings from the PALOMA-3 trial for a community oncologist audience.
Natasha Leighl, MD
For patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) progressing after osimertinib (Tagrisso) and chemotherapy, the PALOMA-3 trial (NCT05388669) compared subcutaneous (SC) amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) to the intravenous (IV) regimen. Results presented at the 2024 IASLC World Conference on Lung Cancer demonstrated pharmacokinetic noninferiority and a significant overall survival (OS) benefit with the SC formulation.1
This phase 3 study evaluated pharmacokinetics, overall response rate (ORR), progression-free survival (PFS), OS, and safety. Findings showed that SC amivantamab met the criteria for noninferiority in pharmacokinetic end points and ORR. In terms of efficacy, the hazard ratios for PFS and OS favored the SC arm, with a statistically significant improvement observed in OS (HR 0.62; 95% CI, 0.42-0.92; P =.02).
The study also showed a significant reduction in chair time for patients receiving SC amivantamab compared with those on the IV formulation. On the first day of treatment, median chair time was 0.4 hours for the SC group vs 6.5 hours for the IV group. This trend continued in subsequent cycles, indicating a substantial improvement in patient convenience. Additionally, health care resource utilization, including active provider time and patient time in the treatment room, was notably lower with the SC administration.
These results led to the FDA granting priority review for the SC formulation of amivantamab in August 2024. However, the FDA issued a complete response letter to the biologics license application submission for amivantamab and SC amivantamab in December 2024.
In an interview with Targeted OncologyTM, Natasha Leighl, MD, MMSc, BSc, clinician investigator and member of the Cancer Clinical Research Unit at Princess Margaret Cancer Centre, discussed key findings from the PALOMA-3 trial for a community oncologist audience.
Holographic concept of lung cancer: © catalin - stock.adobe.com
Targeted Oncology: Can you provide an overview of the PALOMA-3 trial?
Leighl: The PALOMA-3 study was designed to improve the patient experience. We enrolled patients whose cancer had progressed on osimertinib and chemotherapy, in the third-line setting, and patients were randomized either to intravenous amivantamab plus oral lazertinib, a third-generation EGFR [tyrosine kinase inhibitor (TKI)], or subcutaneous amivantamab and lazertinib. The goals of the study were to demonstrate pharmacokinetic noninferiority of the subcutaneous formulation, which we did. We were able to show that, and we also looked at clinical outcomes.
Response rates were about the same. The duration of the response and progression-free survival was longer with subcutaneous amivantamab and lazertinib and, to our surprise, overall survival, which was an exploratory end point, was significantly improved in the group of patients receiving subcutaneous amivantamab and lazertinib, and the hazard ratio was 0.62. We are very excited about that.
Can you discuss the patient experience aspect of the trial?
The initial motivation for the program was to look at improving the patient experience. One of the great things that we presented at [the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting] was that we were able to give amivantamab in less than 5 minutes compared with more than 5 hours for the first day of first dose cycle 1 of intravenous treatment, and about 2 to 3 hours for subsequent doses with the intravenous. A lot of patients liked that and had very high satisfaction. At this meeting, researchers did a wonderful job looking a little bit more deeply into some of the delivery factors and patient satisfaction.
In terms of chair time, patients that received subcutaneous amivantamab spent about 24 minutes on the first day compared with 6 and a half hours in a chair with intravenous amivantamab, and in terms of subsequent doses at cycle 3, it was about 36 minutes compared with 3 and a half hours. A palpable difference, in terms of both what patients experience and the providers. There was less provider time that was required, even though it was a trial, and there was a certain amount of time that patients had to be observed, a marked reduction in how much time our team had to spend looking after patients in the subcutaneous arm than the intravenous arm, and also a marked reduction in time in the treatment room for patients. Patients found this very convenient. The vast majority felt unrestricted by the subcutaneous infusion.
In terms of symptoms, there were very low rates, about 5% or less in terms of swelling or redness at the injection site, and very few patients had any significant pain. More than 85% tolerated it well. Patients also reported that they were satisfied with the subcutaneous formulation, not only initially, but long term. They prefer to receive it, and that increased over the duration of the trial. About 80% of patients would recommend it to other patients. This simplifies the delivery of amivantamab.
The FDA has granted this priority review. It is the first time subcutaneous oncology has actually achieved priority review. We are excited about this, looking forward to making a difference for more patients, making things easier and faster. The other great thing about subcutaneous amivantamab is that we noticed a marked reduction in the risk of infusion-related reactions, from 66% with the intravenous formulation to 13% with the subcutaneous formulation. Again, that leads to time savings for the team, and it makes for a much better patient experience.
For the community oncologist, what are the key findings?
The use of subcutaneous amivantamab has a markedly shorter time of administration, minutes compared with hours with intravenous. [Regarding] pharmacokinetics, efficacy [was] the same to better outcomes for subcutaneous, so there are no disadvantages here. Also, a marked reduction in infusion-related reactions from two-thirds of patients having it cycle 1 day 1 in the first hour to just over 10%, so really a great improvement, both from the patient perspective and from the provider perspective.
We are looking forward to this being available to patients, and I think that when it is, we have also looked at different combinations in the first-line setting with amivantamab, also [in the] first-line setting [with] any chemo, and also a second-line [treatment with] any chemo. Then also for the first-line amivantamab, again, similar outcomes, much better patient experience, fewer [infusion-related reactions], much faster treatment administration.
