SUMMARY

• RYBREVANT (amivantamab-vmjw) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).¹
• LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor (TKI).²
• COCOON (NCT06120140) is an ongoing, phase 2, open-label, randomized study evaluating the impact of enhanced (COCCON dermatologic management [DM] arm) vs standard (standard of care [SoC] DM arm) DM on the incidence of dermatologic adverse events (AEs) among treatment-naïve patients with EGFR-mutated locally advanced or metastatic NSCLC treated with first-line RYBREVANT intravenous (IV) plus LAZCLUZE orally (PO).^3-5 The primary endpoint is the incidence of grade ≥2 dermatologic AEs in the first 12 weeks after treatment initiation with RYBREVANT plus LAZCLUZE.^3,4 Enrollment was planned for approximately 180 patients.³
  • At the interim analysis with a median follow-up of 4.2 months, grade ≥2 dermatologic AEs were reported in 38.6% (27/70) of patients with COCOON DM vs 76.5% (52/68) of patients with SoC DM during the first 12 weeks of treatment (odds ratio [OR], 0.19 [0.09-0.4]; P<0.0001). Grade 3 dermatologic AEs were reported in 4.3% of patients with COCOON DM vs 8.8% of patients with SoC DM.⁴
    • Discontinuation of RYBREVANT or LAZCLUZE due to dermatologic or any AEs was less frequent with COCOON DM than with SoC DM.
  • Patient-reported outcomes (PROs) were evaluated during the first 12 weeks of the COCOON study to assess the impact of dermatologic AE severity on health-related quality of life (QoL).⁶
    • At cycle 3 day 15 (C3D15), a lower average was observed in the total Skindex-16 score (nominal P=0.023) and across all postbaseline subscale scores (functioning, nominal P=0.037; emotional, nominal P=0.046; and symptoms, nominal P=0.011) in patients with COCOON DM vs SoC DM. The endpoint was exploratory and not part of hierarchical hypothesis testing. This endpoint was not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
    • More patients reported mild or no symptoms on the Patient Global Impression of Severity (PGI-S) scale for rash, skin condition, and nail infection with COCOON DM vs SoC DM.

PRODUCT LABELING

• RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.
• LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.

clinical study

COCOON Study

Study Design/Methods

• Ongoing phase 2, open-label, randomized study evaluating the impact of enhanced (COCOON DM arm) vs standard (SoC DM arm) DM on the incidence of dermatologic AEs among treatment-naïve patients with EGFR-mutated locally advanced or metastatic NSCLC treated with first-line RYBREVANT IV plus LAZCLUZE PO.^3-5 
• The study design is shown in Figure: COCOON Study Design.

Girard et al (2025)⁴ reported interim analysis results from the COCOON study evaluating the impact of enhanced (COCOON DM arm) vs standard (SoC DM arm) DM on the incidence of dermatologic AEs.

Results

Patient Characteristics

• At the interim analysis with a median follow-up of 4.2 months, 138 patients (COCOON DM arm, n=70; SoC DM arm, n=68) had received ≥1 dose of RYBREVANT plus LAZCLUZE and had undergone ≥12 weeks of follow-up.⁴
  • The median duration of treatment was 4.2 months with COCOON DM and 4.1 months with SoC DM.
• Patient characteristics and baseline demographics are included in Table: Patient Characteristics and Demographics.

Primary Endpoint

• During the first 12 weeks of treatment, grade ≥2 dermatologic AEs were reported in 38.6% (27/70) of patients with COCOON DM vs 76.5% (52/68) of patients with SoC DM (OR, 0.19 [0.09-0.4]; P<0.0001)⁴; see Table: Dermatologic AEs.

• Dermatologic AEs by body location are included in Table: Grade ≥2 Dermatologic AEs by Body Location.

• Consistent reductions in grade ≥2 dermatologic AEs were observed across all subgroups.⁴ See Table: Clinical Benefit Across Predefined Subgroups.

Secondary Endpoints

Dose Modifications Due to AEs

• Discontinuation of RYBREVANT or LAZCLUZE due to dermatologic or any AEs was less frequent with COCOON DM than with SoC DM⁴; see Table: Dose Modifications of RYBREVANT/LAZCLUZE Due to AEs.
• Venous thromboembolism was observed in 6% of patients with COCOON DM vs 7% of patients with SoC DM.⁴

Feldman et al (2025)⁶ reported PROs from the first 12 weeks of the COCOON study, evaluating the impact of enhanced (COCOON DM arm) vs standard (SoC DM arm) DM on dermatologic AE severity and health-related QoL.

Study Design/Methods

• The severity of dermatologic AEs and their impact on the health-related QoL of patients were measured using PRO instruments every 2 weeks.⁶
  • The validated Skindex-16 questionnaire assessed the impact of dermatologic AEs on health-related QoL using 3 subscales (functioning, emotional, and symptoms) and an average score (0 [no impact] to 100 [impact experienced all the time]). A lower Skindex-16 score corresponds with better QoL and a 10-point change in total score is considered clinically meaningful.
  • The PGI-S scale assessed the severity of rash, skin condition, and nail infection over time using a self-reported, 4-point rating scale (none, mild, moderate, or severe) symptoms.

Results

• At C3D15 (the last time point prior to planned interim analysis at Week 12), a lower average was observed in the total Skindex-16 score (nominal P=0.023) and across all postbaseline subscale scores (functioning, nominal P=0.037; emotional, nominal P=0.046; and symptoms, nominal P=0.011) in patients with COCOON DM vs SoC DM. The endpoint was exploratory and not part of hierarchical hypothesis testing. This endpoint was not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.⁶
• Most patients in the COCOON DM arm did not report moderate or severe symptoms on the PGI-S consistently at all time points up to C3D15.⁶
  • The proportion of patients reporting mild or no symptoms is summarized in Table: Patients Reporting Mild or No Dermatologic Symptoms on PGI-S.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 29 May 2025.