10MO - 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

Background

Dermatologic adverse events (AE) such as rash and paronychia are commonly seen with EGFR inhibitors and usually treated reactively. Phase II COCOON study (NCT06120140) evaluated an enhanced dermatologic prophylactic strategy to determine if skin/nail AEs can be prevented and severity reduced to improve participants (pts) duration of treatment.

Methods

Pts with 1L EGFR-mutant (Ex19del/L858R) advanced NSCLC were randomized 1:1 to receive enhanced dermatologic management (COCOON DM) or standard of care dermatologic management (SoC DM) per site practice. Pts received standard dose IV amivantamab (ami) + oral lazertinib (laz). COCOONDMincluded oral doxycycline/minocycline (100 mg BID Wks 1–12), clindamycin 1% lotion on scalp (QD Wks 13–52), chlorhexidine 4% to wash hands & feet QD, & non-comedogenic ceramide-based moisturizer to body & face QD. Primary endpoint was incidence of grade ≥2 dermatologic AEs of interest (DAEI) by Wk 12. 200 pts would provide 82% power to detect a 35% difference in DAEIs. Prespecified interim analysis (IA) was planned at 70% enrollment (P = 0.014 significance level).

Results

As of 13-Nov-24, 138 pts received COCOON (n = 70) or SoC (n = 68) DM with ami + laz and had ≥12 wks of follow-up (median, 4.2 mo). Median age was 62.5 y; 57% were female. 86% of pts remain on study at clinical cutoff. Primary endpoint was met at this IA. COCOON DM significantly reduced (50%) the incidence of grade ≥2 DAEIs by Wk 12 vs SoC DM (39% vs 76%; OR, 0.19 [95% CI, 0.09–0.40]; P < 0.0001). On COCOON DM, 43/70 pts did not have grade ≥2 DAEIs by Wk 12 vs 16/68 pts on SoC DM, and there was a 50% reduction in grade 3 DAEIs (COCOON DM: 4% vs SoC DM: 9%). A clinically meaningful >3-fold reduction (71%) in scalp grade ≥2 DAEIs by Wk 12 was also observed. AEs leading to dose reductions (10% vs 19%) and discontinuations (11% vs 19%) of ami were meaningfully lower for COCOON vs SoC DM, respectively.

Conclusions

With the simple, widely available, and easy to use COCOON DM regimen, ~2 out of every 3 pts did not experience any moderate to severe dermatologic AEs, and incidence of these skin AEs was reduced by 50% vs SoC DM. This regimen supported pts treatment with 1L ami + laz by reducing ami discontinuations due to AEs by ~50%.

Clinical trial identification

NCT06120140.

Editorial acknowledgement

Medical writing assistance was provided by Nick Harbin, PhD of Lumanity Communications Inc, and was funded by Johnson & Johnson. The authors would like to acknowledge Bothayna Messahel and Bailey G Anderson of Johnson & Johnson.

Legal entity responsible for the study

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Funding

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Disclosure

N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, Beigene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: edimark; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role/Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma, GV20 Therapeutics. J. Feldman: Financial Interests, Personal, Other, Consulting Fees: JNJ, 23 & ME, EQRx; Financial Interests, Personal, Speaker’s Bureau: CME Events, BluePrint Medicine, Takeda, Lumanity (future); Financial Interests, Personal, Other, Travel: Professional Organizations – IASLC, AACR, ASCO, ASTRO, NLCRT, ESMO, NY Lung Cancer Foundation, JNJ; Financial Interests, Personal, Advisory Board: IASLC, EGFR Resisters NLCRT ECOGACRIN. M.P. Mak: Financial Interests, Personal, Speaker’s Bureau: Bayer, Pfizer, Merck Serono, Takeda, Amgen, Eli Lilly, AstraZeneca. M.B. Sauder: Financial Interests, Personal, Other, Consulting Fees: Amgen, Bristol-Myers-Squibb, Incyte, Pharma, Janssen, L’Oreal Canada, Merck, Novartis, Pierre Fabre, Pfizer, Sanofi, Sun Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Canadian Collaborative Research Network, Master Clinical Alliance, Oncology Education, PeerVoice, Master Clinical Alliance. F. Bozorgmehr: Financial Interests, Personal, Advisory Board: Amgen, Janssen, Novartis, AstraZeneca, Novocure, Daiichi Sankyo, BMS; Financial Interests, Personal, Invited Speaker: Novocure, AstraZeneca, MSD, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Janssen; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, GSK, Janssen, Amgen, Roche. J.E. Cundom: Financial Interests, Personal, Other, Consulting Fees, Lung cancer advisory works: MSD; Financial Interests, Personal, Invited Speaker: MSD Argentina, AstraZeneca, Pfizer, Amgen. J.J. Nieva: Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Royalties: Cansera; Financial Interests, Personal, Other, Consulting Fees: Aadi Biosciences, Affyimmune, ANP Technologies, AstraZeneca, Bioatla, G1 Therapeutics, Genenteck, Kalivir, Mindmed, Naveris, Sanofi, Catalym; Financial Interests, Institutional, Other, Travel: AstraZeneca; Financial Interests, Personal, Other, Patent: Human Performance Monitoring; Financial Interests, Personal, Advisory Board: ICON; Financial Interests, Personal, Stocks/Shares: Amgen, Johnson and Johnson, Novartis, Cansera Intragel, Affyimmune, Indee Bio. P. Tomasini: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, BMS, Roche, Janssen, Amgen; Financial Interests, Personal, Other, Travel: Takeda, AstraZeneca, BMS. I. Cicin: Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, MSD, Sanofi, Pfizer, ICON, Janssen, Takeda, Paraxel, Gilead, Novartis, Astra, Jounce, Exelis, Servier; Financial Interests, Personal, Invited Speaker: Yuhan; Other, Personal, Other, Principal investigator for Jounce Therapeutic: Jounce Therapeutic. T. Romero, S. Sheng, J.M. Bauml, J. Simões, P. Mahadevia, M. Wildgust: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. All other authors have declared no conflicts of interest.