Phase II Trial Shows Combination of Rybrevant Plus Lazcluze Significantly Reduces Moderate-to-Severe Skin, Nail Reactions in EGFR-Mutated NSCLC
Results from the COCOON study showed that Rybrevant plus Lacluze reduced grade 2 or higher dermatologic events by 50% compared to standard care in patients with epidermal growth factor receptor-mutated non-small cell lung cancer.
Image Credit: Adobe Stock Images/Ban
Results from the Phase II COCOON study show that Johnson & Johnson's (J&J) preventative dermatologic regimen with Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) significantly reduced moderate-to-severe skin and nail reactions in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).1
“Rybrevant plus Lazcluze helps patients live longer, as seen in the MARIPOSA study, and now we have a way to make the treatment more manageable,” said Pascale Tomasini, MD, PhD, professor in thoracic oncology, multidisciplinary oncology and therapeutic innovations department, Marseille, France, in a press release. “A simple and readily available regimen that reduces dermatologic reactions by half and scalp-related reactions by more than three-fold is a major step forward, potentially allowing patients to stay on treatment longer.”
The randomized, open-label, multicenter COCOON study evaluated the efficacy of the combination therapy in reducing the incidence of skin and nail adverse events (AEs) commonly associated with EGFR-targeted therapies in 201 patients. Patients were randomly assigned into two treatment arms: Arm A received the enhanced combination regimen, while Arm B received standard care.
For the first 12 weeks of the study, patients in Arm A were given either doxycycline or minocycline twice daily, followed by clindamycin 1%, chlorhexidine 4%, and a ceramide-based noncomedogenic moisturizer once daily, in addition to the combination regimen. The primary endpoint was the incidence of grade 2 or higher dermatologic reactions during the first 12 weeks. Key secondary endpoints included the incidence and severity of dermatologic toxicities over the first year, the impact on patients' quality of life, and progression-free survival.
By week 12, 39% of patients in Arm A experienced Grade 2 or higher dermatologic AEs, compared to 77% in Arm B, representing a 50% reduction in dermatologic AEs. Additionally, the incidence of grade 3 skin and nail AEs was halved, dropping from 8.8% in the standard care group to 4.3%. The regimen also demonstrated efficacy in reducing scalp-related grade 2 or higher reactions, achieving a three-fold reduction.
Approximately two-thirds of patients treated with the combination regimen experienced no moderate-to-severe skin-related AEs. Furthermore, only 11% of patients on the regimen discontinued treatment due to AEs, compared to 19% in the standard care group.1
“Being diagnosed with EGFR-positive non-small cell lung cancer is hard enough—none of us signed up for it. But making treatment more manageable from the start makes a big difference,” said Jill Feldman, lung cancer survivor, co-founder, EGFR Resisters, a patient advocacy group, in the press release. “Easing potential dermatologic effects improves the whole treatment experience—allowing us to focus on what really matters: our families, our passions, and truly living.”
Looking ahead, the study will expand to test different treatments for new or ongoing skin reactions in patients receiving Rybrevant and Lazcluze as part of the COCOON regimen. A new group will be added to evaluate whether early intervention with the subcutaneous form of amivantamab, administered every four weeks, can improve outcomes by addressing grade 1 skin and nail reactions before they worsen.1
“Our goal is to help patients get the most out of their Rybrevant-based regimen,” said Mark Wildgust, PhD, VP, oncology global medical affairs, J&J Innovative Medicine, in a press release. “Incorporating simple, preventative steps into daily routines can help manage skin and nail reactions, which may help patients stay on treatment, avoid treatment interruptions and improve their overall treatment experience.”
Reference
1. Easy-to-use preventative regimen demonstrates a statistically significant and clinically meaningful reduction in dermatologic reactions in patients with EGFR-mutated NSCLC. J&J. March 27, 2025. Accessed March 28, 2025. https://innovativemedicine.jnj.com/newsroom/oncology/easy-to-use-preventative-regimen-demonstrates-a-statistically-significant-and-clinically-meaningful-reduction-in-dermatologic-reactions-in-patients-with-egfr-mutated-nsclc
Key Findings of the NIAGARA and HIMALAYA Trials
November 8th 2024In this episode of the Pharmaceutical Executive podcast, Shubh Goel, head of immuno-oncology, gastrointestinal tumors, US oncology business unit, AstraZeneca, discusses the findings of the NIAGARA trial in bladder cancer and the significance of the five-year overall survival data from the HIMALAYA trial, particularly the long-term efficacy of the STRIDE regimen for unresectable liver cancer.
Cell and Gene Therapy Check-in 2024
January 18th 2024Fran Gregory, VP of Emerging Therapies, Cardinal Health discusses her career, how both CAR-T therapies and personalization have been gaining momentum and what kind of progress we expect to see from them, some of the biggest hurdles facing their section of the industry, the importance of patient advocacy and so much more.
