Nicolas Girard, MD
Nicolas Girard, MD, a thoracic oncologist at the Institut Curie, Paris, presented the results of an interim analysis of the open-label phase II COCOON study, at the European Lung Cancer Congress (ELCC) 2025.1 A readily available preventive regimen (the COCOON regimen) reduced moderate-to-severe dermatologic reactions (grade 2 or higher including skin and nail reactions) by 50% in patients receiving first-line treatment with the bispecific monoclonal antibody amivantamab-vmjw and the tyrosine kinase inhibitor lazertinib vs standard dermatologic management.
“Amivantamab plus lazertinib helps patients live longer, as seen in the MARIPOSA study, and now we have a way to make the treatment more manageable,” stated Pascale Tomasini, MD, MSc, Professor in Thoracic Oncology in the Multidisciplinary Oncology and Therapeutic Innovations Department in Marseille, France. “A simple and readily available regimen that reduces dermatologic reactions by half and scalp-related reactions by more than threefold is a major step forward, potentially allowing patients to stay on treatment longer.”
COCOON Trial Details and Results
This phase II, randomized, open-label, multicenter study enrolled newly diagnosed patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations. Patients were given either an enhanced preventive dermatologic regimen (the COCOON regimen, n = 70) or standard dermatologic care (n = 68). The COCOON regimen included a twice-daily oral antibiotic (doxycycline or minocycline at 100 mg); an application of a topical antibiotic for the scalp (clindamycin 1%); an antiseptic wash for the hands and feet, used during regular handwashing or showering (chlorhexidine 4%); and a noncomedogenic ceramide-based moisturizer, applied once daily.
The primary endpoint of the study is the incidence of grade 2 or higher dermatologic reactions within the first 12 weeks of treatment. Key secondary endpoints include the incidence and severity of various dermatologic toxicities during the first year of treatment, their impact on patients’ quality of life, and progression-free survival.
By week 12, patients on the preventive dermatologic regimen had significantly fewer grade 2 or higher dermatologic events compared with standard-of-care management (39% vs 77%; odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.09–0.40; P < .0001), meeting the prespecified endpoint of the study. The incidence of grade 3 dermatologic events was reduced by more than 50% with the preventive regimen (4.3% vs 8.8%). Additionally, scalp-related grade 2 or higher events were reduced by more than threefold, and one patient receiving the preventive dermatologic regimen experienced a grade 3 scalp adverse reaction.
Nearly two out of three patients on the preventive dermatologic regimen had no moderate-to-severe skin-related reactions. Patients receiving this investigational regimen also appeared to experience lower rates of treatment discontinuations (11% vs 19%) on amivantamab and lazertinib caused by any adverse reactions compared with the standard of care.
In addition, the study protocol is being amended to evaluate the impact of different interventions for the treatment of new-onset or persistent dermatologic reactions in patients receiving the COCOON regimen. The study is also expanding to include a new cohort (Cohort C) to evaluate this preventive dermatologic regimen and early intervention with the subcutaneous formulation of amivantamab, administered every 4 weeks. This cohort aims to assess whether initiating reactive treatment at the first signs of skin and nail reactions (grade 1) can further improve outcomes, rather than waiting for symptoms to progress.
DISCLOSURE: For full disclosures of study authors, visit esmo.org. Dr. Tomasini has served as a consultant to Johnson & Johnson but has not been paid for any media work.
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. European Lung Cancer Congress 2025. Abstract 10MO. Presented March 27, 2025.
