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)
Status and phase
Enrolling
Phase 2
Conditions
Carcinoma, Non-Small-Cell Lung
Treatments
Drug: Chlorhexidine
Drug: Amivantamab SC
Drug: Propranolol
Drug: Doxycycline
Drug: Clobetasol
Other: Tacrolimus
Drug: Zinc gluconate
Drug: Timolol
Drug: Minocycline
Other: Noncomedogenic skin moisturizer
Drug: Lazertinib
Other: Ruxolitinib
Drug: Clindamycin
Drug: Amivantamab IV
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
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 and with modified enhanced dermatologic 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. The study also includes an Expansion cohort to evaluate enhanced dermatologic management and early intervention for DAEIs or paronychia, in participants receiving subcutaneous 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.
Enrollment
300 estimated patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
Inclusion criteria
- Have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC); Is treatment naive and not amenable to curative therapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvant therapy for Stage I, Stage II or Stage IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease
- Have a tumor that harbors an epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution, as detected by an Food and Drug Administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site standard-of-care
- A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants with a history of symptomatic brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization, and the participant can be receiving no greater than 10 milligram (mg) prednisone or equivalent daily for the treatment of intracranial disease
- Can have prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints, safety, or the efficacy of the study treatment(s). For the amivantamab SC expansion cohort: Due to the increased risk of skin cancer with ruxolitinib, participants with any prior or concurrent skin malignancies will be excluded
- Sub-study: Participants must have new-onset or persistent (defined as non-responsive to standard of care [SoC]) Grade >=2 specific DAEIs of the scalp, face, or body, as defined by NCI-CTCAE Grading v5.0 for DAEIs (excluding paronychia)
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). For the amivantamab SC expansion cohort, this includes active localized serious infections; 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
- Medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
- Known allergy, hypersensitivity, or intolerance to the excipients of amivantamab, lazertinib, or to tetracyclines, doxycycline, minocycline, timolol*, ruxolitinib*, zinc*, corticosteroids* or their excipients or to any component of the enhanced dermatologic management (*for the amivantamab SC expansion cohort)
- Participant has received any prior systemic treatment at any time for locally advanced stage III B/C or metastatic stage IV disease (adjuvant or neoadjuvant therapy for stage I, II or IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease)
- Participant has an active or past medical history of leptomeningeal disease
- Sub-study: Participants who have received prior treatment for epidermal growth factor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) or calcineurin inhibitors (for Cohort B)
Trial design
Primary purpose
Treatment
Allocation
Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
300 participants in 5 patient groups
Arm A: Enhanced Dermatologic Management
Experimental group
Description:
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).
Treatment:
Drug: Clindamycin
Drug: Amivantamab IV
Drug: Lazertinib
Other: Noncomedogenic skin moisturizer
Drug: Minocycline
Drug: Doxycycline
Drug: Amivantamab SC
Drug: Chlorhexidine
Arm B: Standard-of-Care Dermatologic Management
Active Comparator group
Description:
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.
Treatment:
Drug: Amivantamab IV
Drug: Lazertinib
Other: Noncomedogenic skin moisturizer
Drug: Amivantamab SC
Drug: Chlorhexidine
Sub-study: Cohort A: Ruxolitinib
Experimental group
Description:
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.
Treatment:
Drug: Clindamycin
Drug: Amivantamab IV
Other: Ruxolitinib
Drug: Lazertinib
Other: Noncomedogenic skin moisturizer
Drug: Minocycline
Drug: Doxycycline
Drug: Chlorhexidine
Sub-study: Cohort B: Tacrolimus
Experimental group
Description:
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.
Treatment:
Drug: Clindamycin
Drug: Amivantamab IV
Drug: Lazertinib
Other: Noncomedogenic skin moisturizer
Drug: Minocycline
Other: Tacrolimus
Drug: Doxycycline
Drug: Chlorhexidine
Amivantamab Subcutaneous (SC) Expansion Cohort: Modified Enhanced Dermatologic Management
Experimental group
Description:
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. 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).
Treatment:
Other: Ruxolitinib
Drug: Lazertinib
Other: Noncomedogenic skin moisturizer
Drug: Minocycline
Drug: Timolol
Drug: Zinc gluconate
Drug: Clobetasol
Drug: Doxycycline
Drug: Propranolol
Drug: Amivantamab SC
Drug: Chlorhexidine
Trial contacts and locations
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Central trial contact
Study Contact
Data sourced from clinicaltrials.gov
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