Subcutaneous Amivantamab Shows Promise in Treatment-Naive EGFR-Mutated NSCLC

Nicolas Girard, MD, PhD

The PALOMA-2 study (NCT05498428) investigated the efficacy and safety of a subcutaneous (SC) combination of amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) in patients with previously untreated advanced non–small cell lung cancer (NSCLC) harboring EGFR mutations. Compared with the intravenous (IV) formulation, SC amivantamab significantly reduced infusion-related reactions and administration time.

The study found that the SC combination demonstrated a similar response rate to the historical IV combination. Importantly, the SC formulation was associated with a lower incidence of adverse events, including infusion-related reactions. Prophylactic anticoagulation was effective in reducing the risk of blood clots.

Overall, the results suggest that SC amivantamab in combination with lazertinib is a promising treatment option for patients with EGFR-mutated NSCLC, offering comparable efficacy to the IV formulation with improved convenience and safety.

In an interview with Targeted Oncology^TM, Nicolas Girard, MD, PhD, thoracic oncologist at the Curie Institute in Paris, France, and study investigator on PALOMA-2, discussed findings and implications from this study.

Targeted Oncology: What are the unmet needs in the patient population that PALOMA-2 investigated?

Girard: PALOMA-2 is addressing the formulation of amivantamab, which is a bispecific EGFR antibody, combined with lazertinib, which is a third-generation EGFR [tyrosine kinase inhibitor (TKI)]. [The combination is] improving the outcomes of patients with this disease, especially in the first-line setting which we saw last year as a result from the MARIPOSA trial [NCT04487080]. Even intravenous [amivantamab] plus lazertinib is doing better than the historical standard-of-care, which is Osimertinib [Tagrisso].

Now, the question is how to move forward with the administration of amivantamab. It can be done intravenously, for sure. But given the fact that those patients are usually young patients still working and wanting to have a normal quality-of-life, it is good to have this [subcutaneous] formulation in terms of organizational purposes. It can be done at home.

PALOMA-2 is looking at this patient population of EGFR-mutant non–small cell lung cancer [receiving] first-line treatment, like in MARIPOSA. Response rates are similar to MARIPOSA, 77%. Also, the safety of amivantamab subcutaneously is better than the intravenous formulation, especially in terms of infusion-related reactions, moving from two-thirds of the patients presenting with such reaction with the intravenous formulation to 15% with a subcutaneous formulation. Based on the PALOMA-3 [NCT05388669] data, maybe there is a signal of higher efficacy, at least in the late-line setting with a subcutaneous formulation.

Altogether, it means that this is an important step in the implementation of this combination, especially in the first-line setting because we know it is always better to give the best treatment as early as possible in the management of the patient.

What are the next steps for this research?

Now, it will be a matter of approval. At least in Europe, the subcutaneous formulation will be filled in the indication of intravenous amivantamab. Hopefully, it will be rapidly available for the patient, [and] it will facilitate the implementation of the treatment. There are some challenges regarding the delivery of anticancer agents at the hospital [with] many patients and not enough space for all those patients. Once you do [subcutaneous administration], it is more rapid, both for the patient and organization of the hospital.

Do you foresee the potential for any other combinations using these agents?

We have seen many data with amivantamab recently, including in patients with uncommon mutations besides an EGFR exon 20 mutation. Maybe we can also improve the outcomes of patients in earlier stages of the disease. Amivantamab is a great standard for the patients, and now, we see that we can improve the outcomes through the combination.

REFERENCE:

Lim SM, Tan JL, Dias JM, et al. Subcutaneous amivantamab and lazertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Results from the phase 2 PALOMA-2 study. J Clin Oncol. 2024(suppl 17): abstr LBA8612. doi:10.1200/JCO.2024.42.17_suppl.LBA8612