Enhanced Dermatological Care for Lung Cancer

(COCOON Trial)

Recruiting at 126 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: JAK inhibitors, Calcineurin inhibitors

Disqualifiers: Uncontrolled illness, Interstitial lung disease, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if special skin care can reduce skin and nail problems in people with advanced non-small cell lung cancer (NSCLC) receiving two cancer treatments: amivantamab (Rybrevant) and lazertinib. The study will compare different skin care methods, including standard care, enhanced care, and modified enhanced care, to identify the most effective approach. Participants include those with advanced NSCLC with specific genetic changes (EGFR mutations) who have not yet received treatment for their advanced disease. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must complete any antibiotics at least one week before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amivantamab is generally safe for people with advanced non-small cell lung cancer (NSCLC). Previous studies found it safe to use alone or with chemotherapy. The most common side effects, such as skin rash and infusion reactions, are usually mild and manageable with proper care.

Lazertinib also has a good safety record. Studies indicate it is effective and safe for treating NSCLC with specific EGFR mutations. Most side effects, like rash or diarrhea, are mild to moderate and can often be managed with supportive care.

This trial is in Phase 2, indicating some early evidence that both treatments can be safe for people. The trial will provide more information about their safety and effectiveness when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to managing skin and nail side effects in lung cancer patients. Unlike standard care, which typically involves reactive treatments for skin toxicity, the trial investigates enhanced dermatologic management using antibiotics like doxycycline or minocycline, and topical solutions such as clindamycin and chlorhexidine. Additionally, the study features a unique subcutaneous delivery of amivantamab and involves early intervention strategies with drugs like ruxolitinib and tacrolimus for specific skin adverse events. This proactive and targeted management could potentially improve the quality of life for patients undergoing treatment for EGFR-mutated non-small cell lung cancer.

What evidence suggests that this trial's treatments could be effective for reducing dermatologic adverse events in patients with EGFR-mutated non-small cell lung cancer?

Research shows that combining amivantamab with chemotherapy is more effective than using chemotherapy alone for treating advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations. This combination can significantly extend patient survival. In this trial, participants in Arm A will receive enhanced dermatologic management while undergoing treatment with amivantamab. Lazertinib has proven effective in treating cancer that has spread to the brain in patients with these mutations. Together, amivantamab and lazertinib have changed expectations for survival in initial treatments of this type of lung cancer, suggesting that this combination could be a strong approach to treatment. Participants in Arm B will receive standard-of-care dermatologic management during their treatment with amivantamab and lazertinib. ^{2 3 4 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that hasn't been treated yet and can't be removed by surgery. Participants should have a certain type of mutation in their cancer, be generally well enough to perform daily activities (ECOG 0-1), and could have had brain metastases if treated at least two weeks before the trial. They shouldn't need more than a low dose of steroids for brain symptoms.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My lung cancer is advanced or has spread, and I haven't had treatment for this stage.

My tumor has a specific EGFR mutation.

Exclusion Criteria

History of uncontrolled illness, including but not limited to uncontrolled diabetes; ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting background anticancer treatment] or diagnosed or suspected viral infection); active bleeding diathesis; impaired oxygenation requiring continuous oxygen supplementation; refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of background anticancer treatment or doxycycline/minocycline; psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements; any ophthalmologic condition that is clinically unstable; pre-existing skin condition that would prevent adequate evaluations of dermatologic toxicity, as determined by the investigator

I have or had leptomeningeal disease.

I have a history of lung scarring or inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab and lazertinib with enhanced or standard dermatologic management to reduce dermatologic adverse events

12 weeks

Weekly visits for the first 4 weeks, then bi-weekly

Sub-study

Participants experiencing Grade >= 2 dermatologic adverse events receive reactive treatment with ruxolitinib or tacrolimus

Up to 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Lazertinib

Trial Overview

The study tests whether an enhanced skin care routine reduces skin-related side effects in patients taking Amivantamab and Lazertinib for lung cancer. The enhanced care includes antibiotics like Doxycycline or Minocycline, antiseptic washes, and moisturizers compared to standard skin care practices.

How Is the Trial Designed?

Group I: Sub-study: Cohort B: Tacrolimus Experimental Treatment 8 Interventions

Participants enrolled in Arms A and B of the main study who experience new-onset or persistent specific DAEIs (Grade \>= 2, as defined by NCI-CTCAE v5.0) will be enrolled and receive reactive treatment with tacrolimus in the sub-study. Participants in the sub-study will continue to receive amivantamab and lazertinib.

Group II: Sub-study: Cohort A: Ruxolitinib Experimental Treatment 8 Interventions

Participants enrolled in Arms A and B of the main study who experience new-onset or persistent specific DAEIs (Grade greater than or equal to \[\>=\] 2, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v5.0) will be enrolled and receive reactive treatment with ruxolitinib in the sub-study. Participants in the sub-study will continue to receive amivantamab and lazertinib.

Group III: Arm A: Enhanced Dermatologic Management Experimental Treatment 8 Interventions

Participants will receive enhanced dermatologic management to reduce toxicities in skin and nail with doxycycline tablet or minocycline capsule, clindamycin topical lotion, chlorhexidine topical solution, and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with amivantamab intravenously (Dose 1 for body weight \[BW\] less than 80 kilograms \[kg\] and Dose 2 for BW greater than or equal to \[\>=\] 80 kg as IV infusion \[Arm A\]) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1).

Group IV: Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule Experimental Treatment 11 Interventions

Participants will receive modified enhanced dermatologic management with oral doxycycline or minocycline, zinc gluconate and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic EGFR mutated NSCLC with amivantamab SC and lazertinib as per standard schedule. If a participant develops a dermatologic adverse event of interest (DAEI) they will receive early intervention as follows: for facial (ruxolitinib), for scalp (oral propranolol and clobetasol), for paronychia (chlorhexidine in addition to timolol) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1.

Group V: Amivantamab SC Expansion Cohort: Modified Schedule Experimental Treatment 4 Interventions

Participants will receive modified enhanced dermatologic management with oral doxycycline or minocycline, zinc gluconate and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic EGFR mutated NSCLC with amivantamab SC and lazertinib as per modified schedule. If a participant develops a DAEI they will receive early intervention as follows: for facial (ruxolitinib), for scalp (oral propranolol and clobetasol), for paronychia (chlorhexidine in addition to timolol) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1.

Group VI: Arm B: Standard-of-Care Dermatologic Management Active Control 5 Interventions

Participants will receive standard care for dermatologic management according to local practice to reduce dermatologic toxicities in skin and nail during background anticancer treatment of advanced or metastatic EGFR-mutated NSCLC with amivantamab administered as IV infusion plus lazertinib, dose and dosing schedule as same as experimental arm.

Amivantamab is already approved in United States, European Union for the following indications:

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Amivantamab, a bispecific antibody targeting EGFR and MET, received accelerated FDA approval for treating non-small cell lung cancer (NSCLC) patients with specific EGFR mutations, showing a 40% objective response rate in a Phase I/IB trial with a median response duration of 11.1 months.

In patients with other EGFR mutations, amivantamab alone had a 19% response rate, while combining it with lazertinib improved the response to 36%, indicating potential benefits of combination therapy in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. Petrini, I., Giaccone, G.[2022]

Amivantamab and mobocertinib are FDA-approved treatments for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, showing overall response rates of 40% and 28%, respectively, based on phase 1 and 2 studies involving these specific mutations.

Amivantamab offers a median progression-free survival of 8.3 months, while mobocertinib provides 7.3 months; however, mobocertinib requires cardiac monitoring due to risks of QTc prolongation and cardiac failure, highlighting the importance of safety considerations in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib. Russell, MC., Garelli, AM., Reeves, DJ.[2023]

The combination of amivantamab and lazertinib showed a 36% overall response rate in patients with EGFR-mutant non-small cell lung cancer who had progressed on previous treatments, indicating potential efficacy in a challenging treatment setting.

The safety profile of the combination therapy was consistent with previous studies, with only 4% of patients experiencing severe side effects, suggesting that this treatment may be safe for patients who are chemotherapy naive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Cho, BC., Kim, DW., Spira, AI., et al.[2023]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

The ongoing CHRYSALIS study shows that the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a third-generation EGFR TKI, is effective in treating both treatment-naive patients and those who have relapsed after osimertinib.

The MARIPOSA study is a phase 3 trial designed to compare the safety and efficacy of the amivantamab and lazertinib combination therapy against single-agent osimertinib, aiming to improve first-line treatment outcomes for patients with EGFR-mutant non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Cho, BC., Felip, E., Hayashi, H., et al.[2022]

Targeted therapies and immunotherapies for advanced non-small cell lung cancer (NSCLC) can lead to various skin complications, such as acneiform eruptions from EGFR inhibitors and lichenoid eruptions from PD-1/PD-L1 antibodies.

Most skin-related side effects can be effectively managed with supportive treatments if recognized early, allowing patients to continue their cancer therapy without interruption and improving their overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Dermatologic Complications of Lung Cancer Therapies. Pugliese, SB., Neal, JW., Kwong, BY.[2022]

A systematic review of 24 studies involving 9127 patients with lung cancer revealed that immune checkpoint inhibitors, while effective in treatment, commonly cause cutaneous adverse events, with alopecia occurring in 27% of patients and pruritus and rash in 10%.

Most of the reported skin toxicities were of mild to moderate severity (graded 1-2), indicating that while these side effects are prevalent, they are generally manageable in patients undergoing treatment with drugs like ipilimumab, pembrolizumab, nivolumab, and atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with lung cancer undergoing immune checkpoint inhibitors: A meta-analysis of dermatological toxicities. Garrett, NFMDS., da Costa, ACC., Damiani, G., et al.[2020]

Dacomitinib, a second-generation EGFR-TKI, has been shown to significantly improve overall survival in patients with EGFR mutation-positive non-small cell lung cancer, but it is associated with increased dermatologic adverse events (AEs).

This phase II trial aims to evaluate a proactive management strategy using minocycline, skin moisturizer, topical steroids, and sunscreen to reduce the incidence of grade 2 or higher dermatologic AEs during the first 8 weeks of dacomitinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of a phase II study to evaluate prophylactic treatment of dacomitinib-induced dermatologic adverse events in epidermal growth factor receptor-mutated advanced non-small cell lung cancer (SPIRAL-Daco study). Iwasaku, M., Uchino, J., Yamada, T., et al.[2022]

In a study of 40 patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab, 17% experienced immune-related adverse skin reactions (irAEs), which were linked to better tumor responses.

Among patients who responded to treatment, 42% developed skin irAEs, compared to only 7% of non-responders, suggesting that these skin reactions may indicate a positive therapeutic effect of the immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer. Hasan Ali, O., Diem, S., Markert, E., et al.[2022]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

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News Details - JNJ Investor Relations

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RYBREVANT® (amivantamab-vmjw) HCP

The official healthcare provider website for RYBREVANT® (amivantamab-vmjw), a treatment for EGFR+ mNSCLC. See Full Prescribing & Safety Info.