Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial
- PMID: 40923969
- DOI: 10.1016/j.jtho.2025.07.117
Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial
Abstract
Introduction: Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience.
Methods: In the phase 2 COCOON study (NCT06120140), participants with previously untreated, EGFR-mutant, locally advanced or metastatic NSCLC received intravenous amivantamab plus oral lazertinib and were randomized 1:1 to enhanced dermatologic management (COCOON DM) or standard of care (SoC DM) per local guidelines. COCOON DM included oral doxycycline or minocycline (100 mg twice daily; weeks 1-12), clindamycin 1% (on scalp daily; weeks 13-52), chlorhexidine 4% (on fingernails and toenails daily), and ceramide-based moisturizer (on body and face at least daily). Primary end point was incidence of grade 2 or higher dermatologic AEs of interest (DAEIs) by week 12.
Results: In total, 201 participants were randomized (99 to COCOON DM and 102 to SoC DM). At a median follow-up of 7.1 months, COCOON DM demonstrated significant reduction in the primary end point versus SoC DM (42% versus 75%; OR, 0.24; 95% confidence interval, 0.13-0.45; p < 0.0001). By week 12, the largest benefit with COCOON DM was observed in DAEIs involving the face and body (excludes paronychia; 26% versus 60%; p < 0.0001) and DAEIs involving the scalp (10% versus 26%; p = 0.0049). This benefit was maintained at 6 months, with significant reductions of DAEIs involving face, body, and scalp (excluding paronychia). Patient-reported outcomes favored COCOON DM, indicating reduced impact of dermatologic symptoms on QoL.
Conclusion: An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidence of DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL.
Keywords: Amivantamab; Dermatologic adverse events; Dermatologic management; Lazertinib; Non–small cell lung cancer.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure Dr. Cho served in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Pfizer, Yuhan Corporation, Janssen, Takeda, Merck Sharp & Dohme, Ono Pharmaceutical, Eli Lilly, MedPacto, Blueprint Medicines, Cyrus Therapeutics, Guardant Health, Novartis, CJ Bioscience, Abion, BeiGene, CureLogen, Onegene Biotechnology, GI Cell, HK inno.N, Imnewrun Biosciences, Hanmi, RAND Bioscience, Kanaph Therapeutics, BridgeBio, and Oscotec; served in a leadership role for Interpark Bio and J INTS BIO; holds patents, royalties, or other intellectual property for Champions Oncology, Crown Bioscience, and Imagen; has other relationships with DAAN Biotherapeutics; owns stock or other ownership interests with Theravance, Gencurix, BridgeBio, Kanaph Therapeutics, Cyrus Therapeutics, Interpark Bio, and J INTS BIO; and received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute for Biomedical Research, Dong-A ST, Champions Oncology, Janssen, Yuhan Corporation, Ono Pharmaceutical, Dizal Pharma, Merck Sharp & Dohme, AbbVie, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio, LG Chem, Oscotec, GI Cell, Abion, Boehringer Ingelheim, CJ Bioscience, CJ Blossom Park, Cyrus Therapeutics, Genexine, Nuvalent, Oncternal Therapeutics, Regeneron, BridgeBio, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, J INTS BIO, Hanmi, and CHA Bundang Medical Center. Dr. Spira served in a consulting or advisory role for Array Biopharma, MedImmune, Incyte, Amgen, Novartis, AstraZeneca, Mirati Therapeutics, Gritstone bio, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb, Takeda, Janssen, Mersana, Blueprint Medicines, Daiichi Sankyo, Regeneron, Eli Lilly, Black Diamond Therapeutics, and Sanofi; served in a leadership role for NEXT Oncology; owns stock or other ownership interests with Eli Lilly; received honoraria from CytomX Therapeutics, MedImmune, AstraZeneca, Merck, Takeda, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Bayer; and received research funding from Roche, AstraZeneca, Boehringer Ingelheim, Astellas, MedImmune, Novartis, Incyte, AbbVie, Ignyta, Takeda, MacroGenics, CytomX Therapeutics, LAM Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo Oncology, Arch Therapeutics, Gritstone bio, Plexxikon, Amgen, Daiichi Sankyo, ADC Therapeutics, Janssen, Mirati Therapeutics, Rubius Therapeutics, Synthekine, Mersana, Blueprint Medicines, Regeneron, Alkermes, Revolution Medicines, Medikine, Black Diamond Therapeutics, BluPrint Oncology, NALO Therapeutics, Scorpion Therapeutics, and ArriVent Biopharma. Dr. Sauder served in a consulting role and/or investigator for Alumis, Amgen, AbbVie, Arcutis, Bausch Health, Eli Lilly Canada, Galderma, Incyte Pharma, Janssen, LEO Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, and UCB Canada. Ms. Feldman received consulting fees from Johnson & Johnson, 23andMe, and EQRx; received payment or honoraria from CME Events, Blueprint Medicines, and Takeda; received support for attending meetings and/or travel from IASLC, AACR, ASCO, ASTRO, NLCRT, ESMO, NY Lung Cancer Foundation, and Johnson & Johnson; and served in a leadership role for IASLC, EGFR Resisters, NLCRT, and ECOG-ACRIN. Dr. Bozorgmehr received grants or contracts from Bristol Myers Squibb, Roche, and AstraZeneca; received payment or honoraria from Novocure, Daiichi Sankyo, GlaxoSmithKline, and AstraZeneca; received support for attending meetings and/or travel from Janssen and Roche; and participated on a data safety monitoring board or advisory board for Regeneron, GlaxoSmithKline, Amgen, AstraZeneca, Daiichi Sankyo, and Janssen. Dr. Mak received payment or honoraria from Bayer, Pfizer, Merck Serono, Takeda, Amgen, Eli Lilly, AstraZeneca, and Johnson & Johnson. Dr. Smith received support for attending meetings and/or travel from UC Irvine; participated on a data safety monitoring board or advisory board for the American Academy of Dermatology; and served in a leadership role for the executive board of the Pacific Dermatology Association. Dr. Voon received grants or contracts from AstraZeneca, Novartis, Boehringer Ingelheim, Janssen-Cilag, Johnson & Johnson, Viracta Therapeutics, Inc, Roche, Merck KGaA, Merck Sharp & Dohme, BeiGene, Amgen, and Revolution Medicines; received consulting fees from AstraZeneca, Novartis, Merck Sharp & Dohme, Pfizer, BeiGene, Amgen, Merck KGaA, Janssen-Cilag, and Johnson & Johnson; and received payment or honoraria from AstraZeneca, Novartis, Merck Sharp & Dohme, Pfizer, Amgen, Merck KGaA, Janssen-Cilag, and Johnson & Johnson. Dr. Tan received payment or honoraria from Merck Sharp & Dohme, Boehringer Ingelheim, Johnson & Johnson, Novartis, GlaxoSmithKline, and Pfizer; received support for attending meetings and/or travel from Merck Sharp & Dohme, Takeda, and Pfizer; and received consulting fees from Merck KGaA, GlaxoSmithKline, and Bristol Myers Squibb. Dr. Shih received grants or contracts from Roche, Genconn Biotech, and Taipei City Thoracic Disease Academic Research and Education Foundation; received payment or honoraria from ACT Genomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai, Takeda, CStone Pharmaceuticals, Janssen, TTY Biopharm, Orient EuroPharma, Mundipharma, GlaxoSmithKline, Lotus Pharmaceutical, Ono Pharmaceutical, and Bristol Myers Squibb; received support for attending meetings and/or travel from AstraZeneca, Roche, and Chugai; and participated on a data safety monitoring board or advisory board for Takeda. Dr. Cundom received consulting fees from Merck Sharp & Dohme; and received payment or honoraria from Merck Sharp & Dohme Argentina, AstraZeneca, Pfizer, and Amgen. Dr. Bertollo received support for attending meetings and/or travel from AstraZeneca and Daiichi Sankyo; and received payment or honoraria from AstraZeneca. Dr. Cicin served in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Quintiles; received research funding from Astellas, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Merck KGaA, Parexel, Pfizer, Quintiles, and Taiho. Dr. Nieva received grants or contracts from Merck and Genentech; received royalties or licenses from Cansera; received consulting fees from Aadi Biosciences, ANP Technologies, BioAtla, Genentech, Mindmed, Sanofi, AffyImmune Therapeutics, AstraZeneca, G1 Therapeutics, KaliVir Immunotherapeutics, Naveris, and Catalym; received support for attending meetings and/or travel from AstraZeneca; has patents with Human Performance Monitoring; participated on a data safety monitoring board or advisory board for ICON; and has stock or stock options with Amgen, Novartis, Intragel, Indie Bio, Johnson & Johnson, Cansera, and AffyImmune Therapeutics. Dr. Tomasini received payment or honoraria from AstraZeneca, Takeda, Bristol Myers Squibb, Roche, Janssen, and Amgen; and received support for attending meetings and/or travel from Takeda, AstraZeneca, and Bristol Myers Squibb. Dr. Nguyen received payment or honoraria from Janssen; and served in a leadership or fiduciary role for Gryt Health. Dr. Felip served in a consulting or advisory role for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Pfizer, Sanofi, Takeda, Peptomyc, Daiichi Sankyo Europe GmbH, Roche, Merck Sharp & Dohme, BerGenBio, and Turning Point Therapeutics; participated in speaker bureaus for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dohme, PeerVoice, Pfizer, Takeda, Amgen, Roche, Janssen, Medical Trends, Merck Serono, Sanofi, and TouchONCOLOGY; has other relationships with Grifols; and received research funding from Merck and Merck KGaA. Dr. Schuchard, Mr. Murphy, Ms. Anderson, Dr. Romero, Dr. Xia, Dr. Sheng, Dr. Bauml, Dr. Mahadevia, Dr. Kam, Dr. Nematian-Samani, Dr. Simoes, and Dr. Wildgust are employees of and may hold stock in Johnson & Johnson. Dr. Girard received consulting fees from AbbVie, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Roche, Janssen, LEOPharma, Eli Lilly, Merck Sharp & Dohme, Novartis, Sivan, Mirati Therapeutics, Pfizer, Sanofi, and Takeda; received payment or honoraria from AbbVie, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Roche, Janssen, LEO Pharma, Eli Lilly, Merck Sharp & Dohme, Novartis, Sivan, Mirati Therapeutics, Pfizer, Sanofi, and Takeda; received support for attending meetings and/or travel from Janssen, Amgen, and Bristol Myers Squibb; and participated on a data safety monitoring board or advisory board for Roche. The remaining authors declare no conflict of interest.
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