Advancements in EGFR+ NSCLC Treatment: MARIPOSA and COCOON

Nicolas Girard, MD, PhD

Final overall survival (OS) results from the MARIPOSA trial (NCT04487080) demonstrated a significant OS benefit for the combination of amivantamab-vmjw (Rybrevant) plus lazertinib (Leclaza) compared with osimertinib (Tagrisso) as a first-line treatment for patients with EGFR-mutant advanced non–small cell lung cancer (NSCLC).¹

The median OS with osimertinib was 17 months, while the combination arm showed a more than 12-month difference, with the median not yet reached but the lower boundary of the confidence interval around 43 months (HR, 0.75). These data, which were presented at the 2025 European Lung Cancer Congress (ELCC), suggest that the previously reported progression-free survival (PFS) benefit with the combination translates to a long-term survival advantage, potentially establishing amivantamab plus lazertinib as a new standard of care in this setting.

Separately, data from the COCOON trial (NCT06120140), also presented at ELCC 2025, focused on mitigating the dermatologic adverse events associated with the amivantamab plus lazertinib regimen.² The COCOON trial investigated a prophylactic dermatologic regimen (doxycycline, clindamycin lotion, chlorhexidine, and a ceramide-based moisturizer).

The first interim analysis showed a 2-fold reduction in grade 2 or higher dermatologic adverse events with the prophylactic regimen (39%) compared with standard of care (77%). Further, the prophylactic regimen was associated with lower rates of dose interruption, dose reduction, and discontinuation of amivantamab or lazertinib.

The findings suggest that implementing such prophylactic measures, along with strategies for infusion-related reactions and VTE prophylaxis, can improve the patient experience with the amivantamab plus lazertinib combination.

In an interview with Targeted Oncology^TM, Nicolas Girard, MD, PhD, a thoracic oncologist at the Institut Curie in Paris, France, discussed the results of both trials.

Targeted Oncology: Can you provide some background on the MARIPOSA trial?

Girard: At ELCC 2025, we saw the final overall analysis results from the MARIPOSA trial. MARIPOSA is a first-line EGFR-mutant, non–small cell lung cancer trial that assesses the combination of amivantamab plus lazertinib vs the historical standard of care, which is osimertinib. This is a very large trial that holds more than 1000 patients. The primary end point was progression-free survival, and we saw the results previously with amivantamab plus lazertinib, significantly prolonging progression-free survival vs osimertinib, moving from 17 months with osimertinib to nearly 24 months with amivantamab plus lazertinib. This is a ratio of 0.70, and this led to the approval of MARIPOSA in several countries in Europe.

What specific findings were presented at ELCC?

At ELCC, we have just seen the overall survival results. Overall survival is a very important end point for us because it shows how PFS benefit may translate into prolonged survival for the patients. And actually, at the final overall survival analysis of MARIPOSA, we have a strong benefit with amivantamab plus lazertinib vs osimertinib, more than a 12-month difference between the standard control arm of osimertinib and amivantamab plus lazertinib. This is a hazard ratio of 0.75, and the median overall survival with osimertinib was 17 months.

In line with what was reported historically with amivantamab plus lazertinib, the median is not reached already, but the lower boundary of the confidence interval is about 43 months, so we expect this 12-month difference. So, it shows that the benefits that we have in the first-line setting translate in the long-term to an overall survival benefit, which is at the end, leading amivantamab plus lazertinib to be the new standard of care for the first-line treatment of those patients.

Please provide some background on the COCOON trial.

Amivantamab plus lazertinib is associated with higher incidence of [adverse events], especially dermatological [adverse events], as compared with osimertinib. During the meeting, I [also] presented the results of the COCOON trial. COCOON aimed to assess whether a prophylactic dermatologic regimen could prevent and reduce the incidence of grade 2 or higher dermatologic adverse events using prophylactic agents that are widely available and easy to use. So, the COCOON regimen is doxycycline, clindamycin lotion on the scalp, chlorhexidine on the nails, and a ceramide-based moisturizer on the body and face.

What were the most recent findings presented for this study?

COCOON randomized patients with treatment-naive, EGFR-mutant non–small cell lung cancer to receive the MARIPOSA regimen, either with prophylactic dermatologic management or standard of care, which was often restricted to reactive treatment after toxicity occurred. At the first interim analysis of COCOON, the trial met its primary end point, and we have a 2-fold reduction in the incidence of grade 2 or higher dermatologic adverse events from 77% of the patients with standard of care to 39% of the patients with the COCOON regimen. So, it is clearly changing the way the patients are living with these amivantamab plus lazertinib combinations.

We see that dose interruption, dose reduction, and discontinuation of amivantamab or lazertinib were lower with the COCOON regimen as compared with standard of care, so it clearly is significantly prolonging the overall survival of patients. We expect more patients to receive this combination, but we need to implement these easy to use prophylactic measures to mitigate the [adverse events]. This includes a COCOON regimen for the dermatological adverse events, but also prevention of infusion-related reactions with dexamethasone 3 days before the first injection of amivantamab.

Also, this includes VTE prophylaxis because of a higher risk of VTE in those patients in COCOON. The VTE incidence during the first 12 weeks was low, 6%, when the prophylactic anticoagulation was used, so now we know how to manage the [adverse events] effects of amivantamab. We have an overall survival benefit, so this measure should readily be implemented to improve the patient experience.

Overall, what should community oncologists know about these findings?

The MARIPOSA trial is demonstrating a novel survival benefit with amivantamab plus lazertinib. That is a new standard of care for the first-line treatment of patients with EGFR-mutated non–small cell lung cancer.

REFERENCES:

1. RYBREVANT^® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) significantly outperforms standard of care in first-line EGFR-mutated lung cancer with compelling new data at ELCC 2025. News release. Johnson & Johnson. March 20, 2025. Accessed May 9, 2025. https://tinyurl.com/2pj2mpa4

2. Enhanced preventive regimen demonstrates a statistically significant and clinically meaningful reduction in dermatologic reactions in patients with EGFR-mutated advanced NSCLC. News release. Johnson & Johnson. March 27, 2025. Accessed May 9, 2025. https://tinyurl.com/mvwrmr9b