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A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2)

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ClinicalTrials.gov Identifier: NCT04988295
Recruitment Status : Active, not recruiting
First Posted : August 3, 2021
Last Update Posted : May 22, 2024
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE July 30, 2021
First Posted Date  ICMJE August 3, 2021
Last Update Posted Date May 22, 2024
Actual Study Start Date  ICMJE November 17, 2021
Actual Primary Completion Date July 10, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2024)
Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 28 months ]
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: July 30, 2021)
Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to 17 months ]
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2024)
  • Objective Response as Assessed by BICR [ Time Frame: Up to approximately 28 months ]
    Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria.
  • Overall Survival (OS) [ Time Frame: Up to approximately 48 months ]
    Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
  • Duration of Response (DoR) [ Time Frame: Up to approximately 28 months ]
    DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR.
  • Time to Subsequent Therapy (TTST) [ Time Frame: Up to approximately 28 months ]
    TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first.
  • Progression-Free Survival After First Subsequent Therapy (PFS2) [ Time Frame: Up to approximately 28 months ]
    PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
  • Time to Symptomatic Progression (TTSP) [ Time Frame: Up to approximately 28 months ]
    TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms or death.
  • Intracranial PFS [ Time Frame: Up to approximately 28 months ]
    Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.
  • Intracranial Objective Response Rate (ORR) as Assessed by BICR [ Time Frame: Up to approximately 28 months ]
    Intracranial ORR is defined as the percentage of participants who achieve either an intracranial CR or PR, as defined by BICR using RECIST v1.1.
  • Intracranial Duration of Response (DOR) as Assessed by BICR [ Time Frame: Up to approximately 28 months ]
    Intracranial DoR is defined as the time from the date of first documented intracranial response (PR or CR) until the date of documented intracranial progression or death, whichever comes first, for participants who have intracranial CR or PR.
  • Time to Intracranial Disease Progression as Assessed by BICR [ Time Frame: Up to approximately 28 months ]
    Time to intracranial disease progression is defined as the time from randomization until the date of objective intracranial disease progression, based on BICR using RECIST v1.1.
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Up to'approximately 48 months ]
    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
  • Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to approximately 48 months ]
    Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported.
  • Serum Concentration of Amivantamab [ Time Frame: Up to approximately 28 months ]
    Serum samples will be analyzed to determine concentrations of amivantamab.
  • Plasma Concentration of Lazertinib [ Time Frame: Up to approximately 28 months ]
    Plasma samples will be analyzed to determine concentrations of lazertinib.
  • Number of Participants with Anti-Amivantamab Antibodies [ Time Frame: Up to approximately 28 months ]
    Number of participants with anti-amivantamab antibodies will be reported.
  • Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) [ Time Frame: Up to approximately 28 months ]
    NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology.
  • European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score [ Time Frame: Up to approximately 28 months ]
    The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
  • Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) [ Time Frame: Up to approximately 28 months ]
    PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2021)
  • Objective Response as Assessed by BICR [ Time Frame: Up to 17 months ]
    Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria.
  • Overall Survival (OS) [ Time Frame: Up to 48 months ]
    Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
  • Duration of Response (DoR) [ Time Frame: Up to 17 months ]
    DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR.
  • Time to Subsequent Therapy (TTST) [ Time Frame: Up to 17 months ]
    TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first.
  • Progression-Free Survival After First Subsequent Therapy (PFS2) [ Time Frame: Up to 17 months ]
    PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
  • Time to Symptomatic Progression (TTSP) [ Time Frame: Up to 17 months ]
    TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.
  • Intracranial PFS [ Time Frame: Up to 17 months ]
    Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 48 months ]
    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
  • Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 48 months ]
    Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported.
  • Serum Concentration of Amivantamab [ Time Frame: Up to 17 months ]
    Serum samples will be analyzed to determine concentrations of amivantamab.
  • Plasma Concentration of Lazertinib [ Time Frame: Up to 17 months ]
    Plasma samples will be analyzed to determine concentrations of lazertinib.
  • Number of Participants with Anti-Amivantamab Antibodies [ Time Frame: Up to 17 months ]
    Number of participants with anti-amivantamab antibodies will be reported.
  • Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) [ Time Frame: Up to 17 months ]
    NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology.
  • European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score [ Time Frame: Up to 17 months ]
    The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
  • Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) [ Time Frame: Up to 17 months ]
    PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
Official Title  ICMJE A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure
Brief Summary The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other Names:
    • JNJ-73841937
    • YH-25448
  • Drug: Amivantamab
    Amivantamab will be administered as an IV infusion.
    Other Name: JNJ-61186372
  • Drug: Pemetrexed
    Pemetrexed will be administered as an IV infusion.
  • Drug: Carboplatin
    Carboplatin will be administered as an IV infusion.
Study Arms  ICMJE
  • Experimental: Arm A: LACP/ACP-L
    LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
    Interventions:
    • Drug: Lazertinib
    • Drug: Amivantamab
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Active Comparator: Arm B: CP (Carboplatin and Pemetrexed)
    Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
    Interventions:
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Experimental: Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
    Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
    Interventions:
    • Drug: Amivantamab
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Experimental: Arm A2 (Extension Cohort): ACP-L
    Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
    Interventions:
    • Drug: Lazertinib
    • Drug: Amivantamab
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Experimental: Arm C2 (Extension Cohort): ACP
    Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
    Interventions:
    • Drug: Amivantamab
    • Drug: Pemetrexed
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 12, 2023)
776
Original Estimated Enrollment  ICMJE
 (submitted: July 30, 2021)
500
Estimated Study Completion Date  ICMJE December 8, 2025
Actual Primary Completion Date July 10, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
  • Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
  • A participant with a history of 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 than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
  • Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)
  • A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
  • Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)

Exclusion Criteria:

  • Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
  • Participant with symptomatic or progressive brain metastases
  • Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
  • Participant has known small cell transformation
  • Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
  • Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Czechia,   Denmark,   France,   Germany,   Hong Kong,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Russian Federation,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04988295
Other Study ID Numbers  ICMJE CR109061
2021-001825-33 ( EudraCT Number )
61186372NSC3002 ( Other Identifier: Janssen Research & Development, LLC )
2023-506518-33-00 ( Registry Identifier: EUCT number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency
Current Responsible Party Janssen Research & Development, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Janssen Research & Development, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP