Overview

Proactive therapy management is recommended and may help reduce the risk and severity of select ARs

Mutated EGFR is a critical oncogenic driver for many patients with mNSCLC1

  • Treatments targeting EGFR such as RYBREVANT® or LAZCLUZE™ cause on-target ARs1
  • EGFR inhibitor–related ARs can affect patients’ quality of life1
  • A proactive therapy management approach is needed to give patients the best chance of tolerating and staying on EGFR-targeting treatment2

Evaluating prophylactic strategies for RYBREVANT®-based regimens

SKIPPirr

SKIPPirr was a Phase 2 prospective study that assessed prophylactic strategies to reduce incidence and/or severity of first-dose IRRs with RYBREVANT®, with the dexamethasone 8 mg cohort reaching the expansion stage.* The primary endpoint was the incidence of IRR events on Week 1, Day 1.3,4

Limitations: SKIPPirr was not a comparative study and dexamethasone 8 mg oral cohort sample size was n=40.4

*This was a Simon 2-stage design. Stage 1 n=6. Stage 2 n=16. Expansion stage n=40. See full presentation for more details.4

COCOON

COCOON is an ongoing Phase 2, open-label, randomized study evaluating the effect of enhanced versus standard dermatologic management strategies in patients treated with RYBREVANT® + LAZCLUZE™ in 1L. The primary endpoint is incidence of Grade ≥2 dermatologic ARs of interest in the first 12 weeks after treatment initiation.5

COCOON is also the first trial that required 4 months of prophylactic anticoagulation, with a secondary endpoint of VTE incidence.5,6

*This was a Simon 2-stage design. Stage 1 n=6. Stage 2 n=16. Expansion stage n=40. See full presentation for more details.4

Impact of proactive therapy management

For IRRs: Premedicate with glucocorticoids and consider additional prophylaxis4,7

In the SKIPPirr trial, Cycle 1, Week 1, Day 1 had a

22.5% rate of IRRs.4

In the RYBREVANT® + LAZCLUZE™ arm of MARIPOSA, the rate of IRRs on Cycle 1, Week 1, Day 1 was 52.5%.8

IRR prophylaxis details

For dermatologic ARs: Use skincare prophylaxis and consider the COCOON study5,7

At the time of prespecified interim analysis, COCOON demonstrated a

50% reduction in Grade ≥2 key dermatologic ARs.

  • 38.6% with COCOON prophylactic skincare management vs 76.5% with standard skincare management (primary endpoint) (OR, 0.19 [95% CI: 0.09, 0.4]; P<0.0001)
Dermatologic AR prophylaxis details

For VTE: Use anticoagulants (only when combined with LAZCLUZE™)5*

The COCOON trial required 4 months of VTE prophylaxis.

A 6.5% average rate of VTE

was observed in the patient population with EGFR+ mNSCLC receiving RYBREVANT® + LAZCLUZE™ in 1L.

VTE prophylaxis details

*Based on Prescribing Information for RYBREVANT®.

1L, first-line; AR, adverse reaction; CI, confidence interval; EGFR, epidermal growth factor receptor; IRR, infusion-related reaction; mNSCLC, metastatic non–small cell lung cancer; OR, odds ratio; VTE, venous thromboembolism.

IRRs

Prophylaxis is recommended to help reduce risk of IRRs

Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT® as recommended7

  • Due to the risk of IRRs, administer premedications prior to initial infusion of RYBREVANT® (Week 1, Days 1 and 2)
  • Glucocorticoid administration is required for Week 1, Days 1 and 2 dose only and upon re-initiation after prolonged dose interruptions, then as necessary for subsequent infusions. Administer both antihistamine and antipyretic prior to all infusions.
  • Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity
  • If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®

Additional strategies: SKIPPirr protocol

The SKIPPirr protocol evaluated a strategy to reduce IRR rates on Week 1, Day 1 with RYBREVANT® using prophylactic glucocorticoids.

One cohort tested in SKIPPirr reached the expansion stage: dexamethasone 8 mg oral cohort4,7

†These are given based on RYBREVANT® Prescribing Information recommendations, per the Premedications for RYBREVANT® table.

In SKIPPirr, the Week 1, Day 1 dexamethasone dose is 10 mg IV. In the Prescribing Information for RYBREVANT®, the Week 1, Day 1 dexamethasone dose is 20 mg IV.4,7

IV, intravenous.

SKIPPirr results

In the SKIPPirr dexamethasone 8 mg oral cohort, the incidence rate of patients experiencing IRRs on Week 1, Day 1 was 22.5% (9/40).4

All-Grade IRRs on Week 1, Day 1 infusion (%)4,8

SKIPPirr was not a comparative study.

Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT® as recommended.7

Prophylaxis regimen from the SKIPPirr trial is not included in the Prescribing Information.

Dermatologic ARs

COCOON prophylactic skincare management reduced key dermatologic ARs

COCOON prophylactic skincare management5,9

Weeks 1-12

Oral antibiotic

Doxycycline or minocycline
100 mg
twice daily

Weeks 13+

Topical antibiotic lotion

Topical clindamycin lotion 1% on the scalp before bedtime

Daily

Antiseptic skin cleanser

Chlorhexidine 4% on fingernails and toenails once daily

Moisturizer

Ceramide-based (eg, La Roche-Posay*)
moisturizer on the body and face at least once daily

Ceramide-based, moisturizer on the body and face at least once daily

Limit direct exposure to sunlight

Wear protective clothing and broad-spectrum sunscreen (SPF ≥30)

Wear protective clothing and broad-spectrum sunscreen (SPF ≥30)

The COCOON prophylactic skincare management is not included in the Prescribing Information for RYBREVANT®.

*All trademarks are property of their respective owners.

SPF, sun protection factor.

COCOON results

Primary endpoint: At the time of prespecified interim analysis, COCOON prophylactic skincare management significantly reduced the incidence of Grade ≥2 dermatologic ARs for the first 12 weeks vs standard skincare management by 50% (OR, 0.19 [95% CI: 0.09, 0.4]; P<0.0001)5

  • 4.3% rate of Grade 3 reactions with the COCOON prophylactic skincare management vs 8.8% for patients receiving standard skincare management

Improvements seen with the COCOON prophylactic skincare management across areas of interest5

VTE

Prophylaxis is recommended to prevent VTE

Drug-related prophylaxis for VTE7

Prophylactic treatment with an anticoagulation medicine is recommended for the first 4 months of treatment with RYBREVANT® + LAZCLUZE™.

  • The use of Vitamin K antagonists is not recommended
  • If there are no signs or symptoms of VTE during the first 4 months of treatment, consider discontinuation of anticoagulant prophylaxis at the discretion of the healthcare provider

~97% of patients in the RYBREVANT® + LAZCLUZE™ arm of MARIPOSA did not receive prophylactic anticoagulation for the first 4 months.8

COCOON: VTE results5

COCOON is the first trial that required 4 months of prophylactic anticoagulation at treatment initiation, leading to a low incidence of VTE

A 6.5% average rate of VTE was observed in the patient population with EGFR+ mNSCLC receiving RYBREVANT® + LAZCLUZE™.

Blood clot

VTE, which includes DVT and PE, is a key cause of morbidity among patients with lung cancer10

People living with cancer are at 9 times the risk of developing VTE compared with the general population.11

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations for cancer-associated VTE disease12

Anticoagulant options for VTE prophylaxis for ambulatory patients with cancer include direct oral anticoagulants (DOACs) and low molecular weight heparins (LMWHs).*†‡

*Recommendations derived from clinical trials of ambulatory patients with cancer with high thrombosis risk (>18 years, Khorana VTE Risk Score of ≥2, initiating new course of chemotherapy) and are not included in product labeling. Prophylaxis duration should be 6 months or longer if risk persists.

†Always refer to the NCCN Guidelines® for the comprehensive and most up-to-date recommendations on cancer-associated VTE when considering prophylaxis.

‡When using RYBREVANT® in combination with LAZCLUZE™ please refer to the Prescribing Information for VTE prophylaxis recommendation.

DVT, deep vein thrombosis; NCCN, National Comprehensive Cancer Network; PE, pulmonary embolism.

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References:

  1. Yin X, Zhao Z, Yin Y, et al. Adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis. Clin Transl Sci. 2021;14(3):919-933.
  2. Hofheinz RD, Deplanque G, Komatsu Y, et al. Recommendations for the prophylactic management of skin reactions induced by epidermal growth factor receptor inhibitors in patients with solid tumors. Oncologist. 2016;21(12):1483-1491.
  3. Premedication to reduce amivantamab associated infusion related reactions. ClinicalTrials.gov identifier: NCT05663866. Updated July 17, 2024. Accessed March 19, 2025. https://clinicaltrials.gov/study/NCT05663866
  4. Spira AI, Paz-Ares L, Han J-Y, et al. Brief report: preventing infusion-related reactions with intravenous amivantamab: results from SKIPPirr, a phase 2 study. J Thorac Oncol. Published online January 24, 2025. doi: https://doi.org/10.1016/j.jtho.2025.01.018
  5. Girard N, Li W, Spira AI, et al. Preventing moderate to severe dermatologic adverse events in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib. Presented at: European Lung Cancer Congress 2025; March 26-29, 2025; Paris, France.
  6. Enhanced dermatological care to reduce rash and paronychia in epidermal growth factor receptor (EGRF)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab plus lazertinib (COCOON) ClinicalTrials.gov identifier: NCT06120140. Updated January 5, 2024. Accessed March 14, 2025. https://www.clinicaltrials.gov/study/NCT06120140
  7. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  8. Data on file. Janssen Biotech, Inc.
  9. Cho BC, Girard N, Sauder MB, et al. Enhanced vs standard dermatologic management with amivantamab-lazertinib in advanced NSCLC: phase 2 COCOON Study. Presented at: WCLC; September 7-10, 2024; San Diego, CA.
  10. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020;38(5):496-520.
  11. Mulder FI, Horváth-Puhó, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood. 2021;137(14):1959-1969.
  12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cancer-Associated Venous Thromboembolic Disease V.1.2025 © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 19, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.