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)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 2

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Chlorhexidine; Drug: Doxycycline; Drug: Lazertinib; Drug: Amivantamab; Drug: Clindamycin; Drug: Minocycline; Other: Noncomedogenic skin moisturizer

Study type: Interventional

Funder types: Industry

Identifiers

NCT06120140

61186372NSC2007 (Other Identifier)

2023-505863-35-00 (Registry Identifier)

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 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.

Enrollment: 200 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)
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

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
• 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, or their excipients or to any component of the enhanced dermatologic management
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Arm A and Subcutaneous (SC) Expansion Cohort: 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 (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).

Treatment:

Other: Noncomedogenic skin moisturizer

Drug: Minocycline

Drug: Clindamycin

Drug: Doxycycline

Drug: Lazertinib

Drug: Amivantamab

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 intravenous (IV) infusion plus lazertinib, dose and dosing schedule as same as experimental arm.

Treatment:

Drug: Lazertinib

Drug: Amivantamab