Subcutaneous Amivantamab Plus Lazertinib for Patients With EGFR-Mutated Non-Small Cell Lung Cancer

Nicolas Girard, MD, Curie Institute, Paris, France, discusses results from the PALOMA-2 trial which assessed the efficacy and safety of first-line subcutaneous amivantamab, administered once every 4 weeks, plus lazertinib among patients with EGFR-mutated non-small cell lung cancer (NSCLC). 

These results were presented at the 2025 IASLC World Conference on Lung Cancer (WCLC) in Barcelona, Spain. 

Key Clinical Takeaways 

-       PALOMA-2 Trial Context

o   Subcutaneous (SC) amivantamab every 4 weeks (Q4W) combined with lazertinib in first-line EGFR-mutant NSCLC.

o   Aligns with the MARIPOSA regimen (amivantamab + lazertinib IV every 2 weeks), which has demonstrated PFS and OS benefit and is now a standard of care.

-        Administration Advantage

o   SC administration reduces patient and hospital burden compared to IV dosing.

o   Infusion-related reactions are less frequent with SC versus IV delivery.

-        Efficacy

o   Response rate >80%, comparable to MARIPOSA IV results.

o   Confirms non-inferiority of SC delivery for efficacy endpoints.

-        Safety Profile

o   Cutaneous adverse events remain common; prophylactic dermatologic management not implemented in this cohort.

o   VTE prophylaxis implemented; VTE incidence <10%.

o   Overall tolerability profile supports feasibility of SC dosing.

-       Clinical Implications

o   Evidence supports Q4W subcutaneous amivantamab + lazertinib as a practical and effective alternative to IV administration.

o   Reinforces amivantamab + lazertinib as standard first-line care for EGFR-mutant NSCLC.

Transcript:

I am Nicolas Girard, I was attending WCLC 2025, and during this meeting I presented with coauthors the PALOMA-2 data. 

PALOMA-2 is a clinical trial that assessed amivantamab delivered subcutaneously to patients with EGFR-mutant non-small cell lung cancer. In this cohort, amivantamab was delivered subcutaneously every 4 weeks in combination with lazertinib [in] patients with EGFR common mutations in the first-line setting. 

This is a regimen that is quite similar to the MARIPOSA regimen. [In] MARIPOSA amivantamab plus lazertinib demonstrat[ed] PFS and OS benefit for amivantamab plus lazertinib, which is now a standard of care, and the results of the MARIPOSA trial have been published in the New [England] Journal of Medicine during the congress. Thinking about amivantamab in MARIPOSA, it was delivered intravenously every 2 weeks, so, it's quite a burden for the patients, for the hospital, as those patients are young patients, so we need to facilitate the administration of amivantamab. So, subcutaneous is probably a good way to go. 

In this cohort, we administered amivantamab subcutaneously every 4 weeks in combination with lazertinib and we see a similar efficacy in terms of response rate, higher than 80%, in MARIPOSA and with amivantamab subcutaneous. This data clearly shows the value of subcutaneous administration. In terms of side effects, subcutaneous is better than intravenous as it reduces the risk of infusion-related reaction. We know that amivantamab has to be delivered in conjunction with prophylactic dermatologic management, this is a cocoon regimen, [and] it was not implemented in this cohort. We still see some frequent cutaneous side effects in this study. VTE [venous thromboembolism] prophylaxis was implemented, and we see a very low risk of VTE, below 10% in those patients. 

So, we have some data that support this subcutaneous administration every 4 weeks for amivantamab that reinforces [the] MARIPOSA regimen as a standard of care for the management of these patients. 

This is a moving field, and we have many studies ongoing for patients with EGFR-mutant non-small cell lung cancer: new compounds, we have seen data during the congress with ivonescimab, a bispecific VEGF/PD-1 inhibitor, in the second line setting in combination with chemotherapy. We have seen data with iza-bren, a bispecific ADC [antibody-drug conjugate], so there is a lot to come for the management of patients, and we need to understand the treatment sequences beyond [the] first-line with amivantamab plus lazertinib. 

Source: 

Scott SC, Mourão Dias J, Liu B, et al. PALOMA-2: Subcutaneous amivantamab administered every 4 weeks plus lazertinib in first-line EGFR-mutated advanced NSCLC. Presented at the 2025 IASLC World Conference on Lung Cancer. September 6-9, 2025; Barcelona, Spain. Abstract MA08.05