COCOON Trial Regimen May Decrease Dermatologic AEs in EGFR+ NSCLC

Enrolled patients received either amivantamab plus lazertinib with standard dermatologic management or amivantamab plus lazertinib with enhanced dermatologic management.

Among patients with EGFR-mutant non-small cell lung cancer (NSCLC), amivantamab (Rybrevant) plus lazertinib (Lazcluze) and enhanced dermatologic management significantly reduced the incidence of grade 2 or higher dermatologic adverse effects (AEs), according to phase 2 COCOON trial (NCT06120140) findings presented at the 2025 European Lung Cancer Congress.

"At the first pre-planned interim analysis, the primary end point of COCOON was met,” said Nicolas Girard, MD, PhD, a thoracic oncologist at the Institut Curie in Paris, France, during the presentation of these findings. “We see that the prophylactic COCOON dermatologic management regimen significantly reduced the incidence of grade two or higher dermatologic adverse events. This is a two-fold reduction of these adverse events, a two-fold reduction in grade three dermatologic adverse events, [and] a two-fold reduction in discontinuation due to adverse events, which allows more patients to remain on treatment."

Enrolled patients had EGFR-mutated, treatment-naive NSCLC who had an ECOG score of 0 or 1 and were randomized 1:1 to treatment with amivantinib plus Lazertinib with enhanced dermatologic management (COCOON DM; n = 70) or treatment with amivantinib plus Lazertinib with standard dermatologic management (standard of care; SOC; n = 68). Participants were stratified by age (< 65 or ³ 65) and race (Asian or non-Asian).

The experimental treatment reduced grade 2 or higher dermatologic AEs by 50% compared with SOC amivantamab plus lazertinib and standard dermatologic management. A two-fold reduction in grade 2 or higher dermatologic AEs were observed when compared with SOC (38.6% vs 76.5%, respectively) in the first 12 weeks.

Additionally, there was a two-fold reduction in grade 3 dermatologic AEs with the COCOON DM regimen compared with SOC (4.3% vs 8.8%). The study also reported a three-fold reduction in the number of participants who reported 2 or more grade 2 or higher dermatologic AEs with COCOON DM vs SOC (6% vs 18%).

For dermatologic AEs, 16% of patients receiving COCOON DM experienced dose interruption compared with 34% in the SOC group. Dose reduction occurred in 7% of the COCOON DM group and 19% of the SOC group. Discontinuation due to dermatologic AEs was 1% in the COCOON DM group and 4% in the SOC group.

Dose interruption was reported in 50% of the COCOON DM group and 54% of the SOC group. Dose reduction for any AEs was 21% in the COCOON DM group and 31% in the SOC group. Discontinuation due to any AEs occurred in 11% of the COCOON DM group and 19% of the SOC group.

Venous thromboembolism was observed in 6% of participants with COCOON DM and 7% with SOC.

The COCOON DM regimen included an oral doxycycline or minocycline for 12 weeks followed by topical clindamycin lotion on the scalp. Additionally, chlorhexidine was administered to the nails and ceramide-based moisturizer was applied to the body and face.

The SOC regimen included general skin prophylaxis per local practice and reactive treatment, such as topical corticosteroids and systemic antibiotics.

At a median follow-up of 4.2 months, 138 participants received at least one dose of Rybrevant plus Lazcluze (safety analysis set) and had at least 12 weeks of follow-up. The median duration of Rybrevant plus Lazcluze treatment was 4.2 months with COCOON DM, compared to 4.1 months with SOC.

The median age of participants in both the COCOON DM and SoC DM groups was 62.5 years. In the COCOON DM group, 42 participants were female (60%), compared to 37 (54%) in the SOC group.

In the COCOON DM group, 35 participants (50%) had EGFR mutations of Ex19del vs 37 patients (54%) in the SOC group. L858R mutations was reported in 35 participants (50%) in the COCOON DM group and 31 (46%) in the SOC group.

The primary end point was the incidence of grade 2 or higher dermatologic AEs in the first 12 weeks after initiation of Rybrevant plus Lazcluze treatment.

First-line Rybrevant plus Lazcluze is Food and Drug Administration, and European Medicines Agency approved for EGFR-mutant advanced non-small cell lung cancer based on results from the phase 3 MARIPOSA study.

The COCOON trial is now fully enrolled with 201 patients and additional results are planned to be presented at upcoming congresses.

Reference

1. Girard N, Li W, Spira A, et al. Preventing moderate to severe dermatologic adverse events in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Early success of the COCOON trial. Presented at: 2025 European Lung Cancer Congress; March 26-29, 2025; Paris, France. Abstract 10MO.