A Phase 2, Open-Label, Randomized Trial Evaluating the Impact of Enhanced Versus Standard Dermatologic Management on Selected Dermatologic Adverse Events Among Patients With Locally Advanced or Metastatic EGFR-Mutated NSCLC Treated First-Line With Amivantamab + Lazertinib
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 305
- 试验地点
- 172
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
研究组 & 干预措施
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Noncomedogenic skin moisturizer (Other)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Amivantamab SC (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Chlorhexidine (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Lazertinib (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Chlorhexidine (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Lazertinib (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Clindamycin (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Minocycline (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Ruxolitinib (Other)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Doxycycline (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Tacrolimus (Other)
Amivantamab SC Expansion Cohort: Modified Schedule
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.
干预措施: Amivantamab SC (Drug)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Chlorhexidine (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Doxycycline (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Zinc gluconate (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Propranolol (Drug)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Minocycline (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Lazertinib (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Minocycline (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Timolol (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Chlorhexidine (Drug)
Amivantamab SC Expansion Cohort: Modified Schedule
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.
干预措施: Doxycycline (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Clobetasol (Drug)
Amivantamab SC Expansion Cohort: Modified Schedule
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.
干预措施: Lazertinib (Drug)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Amivantamab IV (Drug)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Noncomedogenic skin moisturizer (Other)
Arm B: Standard-of-Care Dermatologic Management
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.
干预措施: Amivantamab IV (Drug)
Arm B: Standard-of-Care Dermatologic Management
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.
干预措施: Noncomedogenic skin moisturizer (Other)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Noncomedogenic skin moisturizer (Other)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Amivantamab IV (Drug)
Sub-study: Cohort A: Ruxolitinib
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.
干预措施: Amivantamab IV (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Noncomedogenic skin moisturizer (Other)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Lazertinib (Drug)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Doxycycline (Drug)
Arm B: Standard-of-Care Dermatologic Management
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.
干预措施: Lazertinib (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Clindamycin (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Doxycycline (Drug)
Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule
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.
干预措施: Ruxolitinib (Other)
Arm A: Enhanced Dermatologic Management
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).
干预措施: Clindamycin (Drug)
Sub-study: Cohort B: Tacrolimus
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.
干预措施: Minocycline (Drug)
Arm B: Standard-of-Care Dermatologic Management
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.
干预措施: Chlorhexidine (Drug)
Amivantamab SC Expansion Cohort: Modified Schedule
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.
干预措施: Minocycline (Drug)
结局指标
主要结局
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
时间窗: 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.
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
时间窗: 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.
次要结局
- 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 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 Grade >= 2 DAEI Per Participants(Up to 12 months)
- Time to First Occurrence of Grade >=2 DAEI(Up to 12 months)
- Time to Resolution of Grade >= 2 DAEI(Up to 12 months)
- 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 Scalp Rash by Severity Based on NCI-CTCAE v 5.0(Up to 12 months after initiation of anticancer treatment)
- Change From Baseline in Skindex Symptoms Domain Score up to 12 Months(Baseline, up to Month 12)
- 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 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 EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only)(Baseline, up to Month 12)
- Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs(Up to 12 months)
- Relative Dose Intensity (RDI) of Anticancer Treatment(Up to 12 months)
- 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 Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0(Up to 12 months)
- Progression Free Survival (PFS)(Up to 12 months)
- Overall Response Rate (ORR)(Up to 12 months)
- Duration of Response (DoR)(Up to 12 months)
- 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 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 Grade >= 2 DAEI Per Participants(Up to 12 months)
- Time to First Occurrence of Grade >=2 DAEI(Up to 12 months)
- Time to Resolution of Grade >= 2 DAEI(Up to 12 months)
- 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 Scalp Rash by Severity Based on NCI-CTCAE v 5.0(Up to 12 months after initiation of anticancer treatment)
- Change From Baseline in Skindex Symptoms Domain Score up to 12 Months(Baseline, up to Month 12)
- Overall Response Rate (ORR)(Up to 12 months)
- Amivantamab SC Expansion Cohorts: Percentage of Participants With an Improvement in DAEI After Starting Early Intervention(Up to 12 months)
- 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 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 EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only)(Baseline, up to Month 12)
- Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0(Up to 12 months)
- Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs(Up to 12 months)
- Relative Dose Intensity (RDI) of Anticancer Treatment(Up to 12 months)
- Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0(Up to 12 months)
- Progression Free Survival (PFS)(Up to 12 months)
- Duration of Response (DoR)(Up to 12 months)
- 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)
- Amivantamab SC Expansion Cohorts: Time to Improvement of DAEIs After Starting Early Intervention(Up to 12 months)