COCOON Trial Regimen Reduces Dermatologic Side Effects in Mutated Lung Cancer

Among patients with EGFR-mutant non-small cell lung cancer, the COCOON trial regimen (Rybrevant [amivantamab] plus Lazcluze [lazertinib] plus enhanced dermatologic management) significantly reduced the incidence of grade 2 (moderate) or higher dermatologic side effects, according to phase 2 COCOON study 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 Dr. Nicolas Girard 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 [side effects]. This is a two-fold reduction of these [side effects], a two-fold reduction in grade three dermatologic [side effects and] a two-fold reduction in discontinuation due to [side effects], which allows more patients to remain on treatment."

The trial found that the COCOON trial, also referred to as COCOON DM, reduced grade 2 or higher dermatologic side effects by 50% compared with the standard of care (Rybrevant plus Lazcluze plus standard dermatologic management). A two-fold reduction in grade 2 or higher dermatologic side effects were observed when compared with standard of care (38.6% versus 76.5%, respectively) in the first 12 weeks.

Additionally, there was a two-fold reduction in grade 3 (severe) dermatologic side effects with COCOON DM compared with standard of care (4.3% versus 8.8%). The study also reported a three-fold reduction in the number of participants who reported two or more different grade 2 or higher dermatologic side effects with COCOON DM versus standard of care (6% versus 18%).

For dermatologic side effects, 16% (11 patients) of patients receiving COCOON DM experienced dose interruption compared with 34% (23 patients) in the standard of care group. Dose reduction occurred in 7% (5 patients) of the COCOON DM group and 19% (13 patients) of the standard of care group. Discontinuation due to dermatologic side effects was 1% (1 patient) in the COCOON DM group and 4% (3 patients) in the standard of care group.

When considering any side effects, dose interruption was reported in 50% (35 patients) of the COCOON DM group and 54% (37 patients) of the standard of care group. Dose reduction for any side effects was 21% (15 patients) in the COCOON DM group and 31% (21 patients) in the standard of care group. Discontinuation due to any side effects occurred in 11% (8 patients) of the COCOON DM group and 19% (13 patients) of the standard of care group.

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

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 standard of care 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 standard of care.

The median age of participants in both the COCOON DM (70 patients) and SoC DM (68 patients) groups was 62.5 years. In the COCOON DM group, 42 participants were female (60%), compared to 37 (54%) in the standard of care group.

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

The primary end point was the incidence of grade 2 or higher dermatologic side effects 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.

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