Enhanced Dermatological Care for Lung Cancer

(COCOON Trial)

Recruiting at 98 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate whether enhanced dermatologic management can reduce incidence of grade greater than or equal to (\>=) 2 dermatologic adverse events of interest (DAEIs) when compared with standard-of-care skin management in participants with locally advanced or metastatic stage IIIB/C-IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab and lazertinib. A substudy will enroll participants from Arms A and B who experience specific new-onset or persistent DAEIs (Grade \>=2) during treatment with intravenous (IV) amivantamab and lazertinib. This substudy aims to assess the reactive use of dermatologic treatment strategies in these participants.

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.

What data supports the effectiveness of the drug Amivantamab, Rybrevant, amivantamab-vmjw, JNJ-61186372, Lazertinib, Lazcluze for lung cancer?

Research shows that the combination of amivantamab and lazertinib is effective in treating non-small cell lung cancer, especially in patients who have relapsed after other treatments. Studies have demonstrated significant tumor reduction and prolonged response times in patients with specific genetic mutations. ^{1 2 3 4 5}

Is the combination of Amivantamab and Lazertinib safe for humans?

The combination of Amivantamab and Lazertinib has been tested in clinical trials for lung cancer, and the safety profile was generally consistent with previous experiences of each drug alone, with only 4% of patients experiencing severe side effects. No new safety concerns were identified. ^{1 2 3 4 6}

What makes the drug Amivantamab and Lazertinib unique for lung cancer treatment?

Amivantamab and Lazertinib are unique because they target specific genetic mutations in lung cancer cells, potentially offering a more personalized treatment approach compared to traditional therapies. This combination may provide an alternative for patients who have specific genetic profiles, which can lead to more effective and tailored treatment outcomes. ^{7 8 9 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 0.1% ointment twice daily for up to 12 weeks 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 1.5% cream twice daily for up to 12 weeks in the sub-study. Participants in the sub-study will continue to receive amivantamab and lazertinib.

Group III: Arm A and Subcutaneous (SC) Expansion Cohort: 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 (100 milligrams \[mg\] twice daily for 12 weeks), clindamycin 1 percent (%) topical lotion, chlorhexidine 4% topical solution, and noncomedogenic skin moisturizer (once daily) during background anticancer treatment of advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with amivantamab (1050 mg for body weight \[BW\] less than 80 kilograms \[kg\] and 1400 mg for BW greater than or equal to \[\>=\] 80 kg as IV infusion \[Arm A\], once weekly for the first 4 weeks, then once every 2 weeks) and subcutaneously (expansion cohort) (cycle 1: 1600 mg or 2240 mg once weekly based on BW; cycles 2 onwards: 3520 mg or 4640 mg based on BW on Day 1 of each 28-day cycle) with lazertinib (240 mg, tablet, once daily) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1).

Group IV: 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 intravenous (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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]

2. England 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. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. [2022]

4. England pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Patients with lung cancer undergoing immune checkpoint inhibitors: A meta-analysis of dermatological toxicities. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]

10. China 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). [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Management of Dermatologic Complications of Lung Cancer Therapies. [2022]