A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy

ClinicalTrials.gov processed this data on October 23, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING (See Contacts and Locations)
Verified October 2024 by Janssen Research & Development, LLC

Sponsor

Janssen Research & Development, LLC

Information Provided by (Responsible Party)

Janssen Research & Development, LLC

Clinicaltrials.gov Identifier

NCT05388669
Other Study ID Numbers: CR109211
First Submitted: May 19, 2022
First Posted: May 24, 2022
Last Update Posted: October 24, 2024
Last Verified: October 2024
History of Changes

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Tracking Information
First Submitted DateMay 19, 2022
First Posted DateMay 24, 2022
Last Update Posted DateOctober 24, 2024
Study Start DateAugust 5, 2022
Actual Primary Completion DateJanuary 3, 2024
Current Primary Outcome Measures
(submitted: October 23, 2024)
  1. For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1 [Cycle 4 Day 1 (28 days cycle)]
    Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.
  2. For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1 [Cycle 2 Day 1 (28 days cycle)]
    Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.
  3. Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2 [Cycle 2 Day 1 to Cycle 2 Day 15 (28 days cycle)]
    AUC(Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15, will be reported.
Change HistoryComplete list of historical versions of study NCT05388669 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
  1. Objective Response Rate (ORR) [Up to 1 year 11 months]
    ORR is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1).
  2. Progression-Free Survival (PFS) [Up to 1 year 11 months]
    PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1.
  3. Duration of Response (DOR) [Up to 1 year 11 months]
    The DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.
  4. Time to Response (TTR) [Up to 1 year 11 months]
    Time to response (that is time to first response) is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, as defined by BICR using RECIST version 1.1., for participants who have PR or CR as their best response.
  5. Number of Participants With Adverse Events (AEs) [Up to 4 year 11 months]
    An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.
  6. Number of Participants with AEs by Severity [Up to 4 year 11 months]
    Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 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. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.
  7. Number of Participants with Clinical Laboratory Abnormalities [Up to 4 year 11 months]
    Number of participants with clinical laboratory abnormalities (serum Chemistry, hematology, coagulation, and urinalysis) will be reported. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.
  8. Number of Participants with Clinical Laboratory Abnormalities by Severity [Up to 4 year 11 months]
    Number of participants with clinical laboratory abnormalities by severity (serum Chemistry, hematology, coagulation, and urinalysis) will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 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. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.
  9. Number of Participants Infusion Related Reactions (IRRs) [Up to 1 year 11 months]
    Number of participants with IRRs will be reported.
  10. Number of Participants with Infusion Related Reactions (IRRs) by Severity [Up to 1 year 11 months]
    Number of participants with IRRs by severity will be reported.
  11. For All Regions Other Than the EU and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1 [Cycle 2 Day 1 (28 days cycle)]
    The Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.
  12. For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1 [Cycle 4 Day 1 (28 days cycle)]
    The Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.
  13. Model-Predicted Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab at Steady State of Cycle 4 [From Cycle 4 Day 1 to Cycle 4 Day 15 (28 days cycle)]
    Model-predicted AUC(Day 1-15) defined as area under the concentration time curve from Cycle 4 Day 1 to Day 15, will be reported.
  14. Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies [Up to 1 year 11 months]
    Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.
  15. Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ) [Up to 1 year 11 months]
    Percentage of participants with cancer therapy satisfaction in will be assessed using the modified TASQ. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.
  16. Change from Baseline in TASQ as Assessed Over Time [Up to 1 year 11 months]
    Change from baseline in TASQ as assessed Over time will be reported. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.
  17. Participant Chair Time [Up to 1 year 11 months]
    Participant chair time will be assessed by time and motion analysis.
  18. Duration of Treatment Administration [Up to 1 year 11 months]
    Duration of treatment administration will be assessed by time and motion analysis.
  19. Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring [Up to 1 year 11 months]
    Active health care professional time for drug preparation, treatment administration, and posttreatment monitoring will be assessed by time and motion analysis.
  20. Participant Time in Treatment Room [Up to 1 year 11 months]
    Participant time in treatment room will be assessed by time and motion analysis.
Current Other Outcome MeasuresNot Provided
Descriptive Information
Brief TitleA Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer
Official TitleA Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy
Brief SummaryThe purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Target Follow-Up DurationNot Provided
BiospecimenNot Provided
Sampling MethodNot Provided
Study PopulationNot Provided
Condition
  • Advanced or Metastatic Non-small Cell Lung Cancer
Intervention

Drug: Lazertinib

Lazertinib tablets will be administered orally.

Study Groups/Cohorts

Experimental: Arm A: Lazertinib with Amivantamab SC-CF
Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.

Intervention:
  • Drug: Lazertinib
  • Drug: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)

Experimental: Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion
Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.

Intervention:
  • Drug: Lazertinib
  • Drug: Amivantamab Intravenous
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 StatusActive, not recruiting
Actual Enrollment
(submitted: October 23, 2024)
418
Anticipated Study Completion DateDecember 31, 2025
Actual Primary Study Completion DateJanuary 3, 2024
Eligibility Criteria

Inclusion Criteria:

  • Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by an Food and Drug Administration (FDA)-approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United Started [US]) or an accredited local laboratory (sites outside of the US)
  • Have progressed on or after osimertinib (or another approved 3rd generation epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]) and platinum-based chemotherapy (irrespective of order). a) The 3rd generation EGFR TKI must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. b) Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. c) Any adjuvant or neoadjuvant treatment, whether with a 3rd generation EGFR TKI or platinum based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease
  • Have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) version 1.1
  • Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
  • Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade less than or equal to (<=) 2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement)

Exclusion Criteria:

  • Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors
  • Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization
  • Participant has symptomatic or progressive brain metastases
  • Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
  • Participant has uncontrolled tumor-related pain
  • Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis

Sex/GenderSexes Eligible for Study: All
Ages18 Years and Older (Adult, Older Adult)
Accepts Healthy VolunteersNo
ContactsContact information is only displayed when the study is recruiting subjects
Listed Location CountriesUnited States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, Argentina, Argentina, Argentina, Argentina, Argentina, Argentina, Australia, Australia, Australia, Australia, Australia, Australia, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Brazil, Canada, Canada, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, China, France, France, France, France, Germany, Germany, Germany, Germany, Germany, Germany, Israel, Israel, Israel, Israel, Israel, Italy, Italy, Italy, Italy, Italy, Italy, Italy, Italy, Italy, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Korea, Republic of, Malaysia, Malaysia, Malaysia, Malaysia, Malaysia, Malaysia, Poland, Poland, Poland, Poland, Poland, Portugal, Portugal, Portugal, Portugal, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Spain, Taiwan, Taiwan, Taiwan, Taiwan, Taiwan, Taiwan, Taiwan, Taiwan, Thailand, Thailand, Thailand, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, Turkey, United Kingdom, United Kingdom, United Kingdom, United Kingdom
Administrative Information
NCT NumberNCT05388669
Other Study ID NumbersCR109211
Has Data Monitoring CommitteeYes
U.S FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes

Studies a U.S. FDA-regulated Device Product: No

Product Manufactured in and Exported from the U.S.: Not Provided

IPD Sharing StatementPlan to Share IPD: Yes
Responsible PartyJanssen Research & Development, LLC, Janssen Research & Development, LLC
Study SponsorJanssen Research & Development, LLC
CollaboratorsNot Provided
Investigators
PRS AccountJanssen Research & Development, LLC
Verification DateOctober 2024