Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
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 Expansion cohorts (in 2 different schedules) 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.
Interventions
DRUGAmivantamab IV
Amivantamab will be administered.
DRUGAmivantamab SC
Amivantamab will be administered as SC injection.
DRUGLazertinib
Lazertinib tablet will be administered orally.
DRUGDoxycycline
Doxycycline tablet will be administered orally.
DRUGMinocycline
Minocycline capsule will be administered orally.
DRUGClindamycin
Clindamycin lotion will be used as topical application on the scalp.
DRUGChlorhexidine
Chlorhexidine solution will be used as topical application on hands and feet.
OTHERNoncomedogenic skin moisturizer
Noncomedogenic skin moisturizer will be used as topical application.
OTHERRuxolitinib
Ruxolitinib will be used to the affected skin area.
OTHERTacrolimus
Tacrolimus will be used as topical application to the affected skin area.
DRUGZinc gluconate
Zinc gluconate tablet will be administered.
DRUGPropranolol
Propranolol tablet will be administered.
DRUGTimolol
Timolol will be used to the affected skin area.
DRUGClobetasol
Clobetasol shampoo will be used on the scalp.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 cohorts: 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 cohorts, 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 cohorts) * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade Greater Than or Equal to (>=) 2 Dermatologic Adverse Events of Interest (DAEIs) Within 12 Weeks After Initiation of Anticancer Treatment | Up to 12 weeks after initiation of anticancer treatment | Number of participants with Grade \>= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With DAEIs by Severity Based on NCI-CTCAE v 5.0 | Up to 12 weeks after initiation of anticancer treatment | Number of participants with DAEIs by severity based on NCI-CTCAE v 5.0 will be reported. |
| Number of Participants With Grade >=2 DAEIs Within 6 Months After Initiation of Anticancer Treatment Based on NCI-CTCAE v 5.0 | Up to 6 months after initiation of anticancer treatment | Number of participants with Grade \>=2 DAEIs within 6 months after initiation of anticancer treatment based on NCI-CTCAE v 5.0 will be reported. |
| Number of Grade >= 2 DAEI Per Participants | Up to 12 months | Number of grade \>= 2 DAEI per participants will be reported. |
| Time to First Occurrence of Grade >=2 DAEI | Up to 12 months | Time to first occurrence of Grade \>=2 DAEI will be reported. |
| Time to Resolution of Grade >= 2 DAEI | Up to 12 months | Time to resolution of Grade \>= 2 DAEI will be reported. |
| Number of Participants With Paronychia by Severity Based on NCI-CTCAE v 5.0 | Up to 6 months after initiation of anticancer treatment | Number of participants with paronychia by severity based on NCI-CTCAE v 5.0 will be reported. |
| Number of Participants With Scalp Rash by Severity Based on NCI-CTCAE v 5.0 | Up to 12 months after initiation of anticancer treatment | Number of participants with scalp rash by severity based on NCI-CTCAE v 5.0 will be reported. |
| Change From Baseline in Skindex Symptoms Domain Score up to 12 Months | Baseline, up to Month 12 | Change from baseline in skindex symptoms domain score up to 12 months will be reported. The score of quality of life will be assessed using the Skindex-16 questionnaire. Skindex-16 is used for participants to rate skin conditions. |
| Change From Baseline in Patient's Global Impression-Severity (PGI-S) Rash up to 12 Months | Baseline, up to Month 12 | Change from baseline in PGI-S rash up to 12 months will be reported. Participant quality of life will be evaluated using PGI-S Rash. PGI-S is a single-item questionnaire assessing participants disease severity on a 7-point response scale. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score up to 12 Months | Baseline, up to Month 12 | Change from baseline in EORTC-QLQ-C30 score up to 12 months will be reported. EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. |
| Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only) | Baseline, up to Month 12 | The EQ-5D questionnaire is a brief, generic HRQOL assessment that can that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1), EQ-5D visual analog scale (VAS) is a vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 \[no limitation\] to 4 \[incapacity\]). |
| Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs | Up to 12 months | Percentage of participants with dose reductions, dose interruptions, and dose discontinuations of anticancer treatment due to DAEIs will be reported. |
| Relative Dose Intensity (RDI) of Anticancer Treatment | Up to 12 months | Relative dose intensity of anticancer treatment will be reported. The relative dose intensity is defined as the ratio of total actually received dose versus total prescribed dose. |
| Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0 | Up to 12 months | Percentage of participants with VTE AEs (pulmonary embolism and deep vein thrombosis) by severity based on NCI-CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0 | Up to 12 months | Percentage of participants with AEs by severity based on NCI-CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Progression Free Survival (PFS) | Up to 12 months | PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause, whichever occurs first. |
| Overall Response Rate (ORR) | Up to 12 months | ORR is defined as the percentage of participants who achieve a partial response (PR) or better response using RECIST v1.1 as assessed by the investigator. |
| Duration of Response (DoR) | Up to 12 months | DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the RECIST v1.1 response criteria. |
| Amivantamab SC Expansion Cohorts: Number of Participants With Grade >= 2 DAEIs Within 12 Weeks After Initiation of Anticancer Treatment | Up to 12 weeks after initiation of anticancer treatment | Participants with Grade \>= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on NCI-CTCAE v 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event. |
| Amivantamab SC Expansion Cohorts: Percentage of Participants With an Improvement in DAEI After Starting Early Intervention | Up to 12 months | Percentage of participants showing an improvement in DAEI by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event. |
| Amivantamab SC Expansion Cohorts: Time to Improvement of DAEIs After Starting Early Intervention | Up to 12 months | Time to improvement of DAEIs by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event. |
Countries
Argentina, Brazil, China, France, Germany, Malaysia, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed