Brief Summary
The 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.
Brief Title
A 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
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Advanced or Metastatic Non-small Cell Lung Cancer
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
* 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
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05388669
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR109211
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.
Outcome Measure
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
Outcome Time Frame
Cycle 4 Day 1 (28 days cycle)
Outcome Description
Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.
Outcome Measure
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1
Outcome Time Frame
Cycle 2 Day 1 (28 days cycle)
Outcome Description
AUC(Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15, will be reported.
Outcome Measure
Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2
Outcome Time Frame
Cycle 2 Day 1 to Cycle 2 Day 15 (28 days cycle)
Secondary Ids
Secondary Id
61186372NSC3004
Secondary Id
2022-000525-25
Secondary Id
2024-512045-16-00
Secondary Outcomes
Outcome Description
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).
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Objective Response Rate (ORR)
Outcome Description
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.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Progression-Free Survival (PFS)
Outcome Description
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.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
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.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Time to Response (TTR)
Outcome Description
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.
Outcome Time Frame
Up to 4 year 11 months
Outcome Measure
Number of Participants With Adverse Events (AEs)
Outcome Description
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.
Outcome Time Frame
Up to 4 year 11 months
Outcome Measure
Number of Participants with AEs by Severity
Outcome Description
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.
Outcome Time Frame
Up to 4 year 11 months
Outcome Measure
Number of Participants with Clinical Laboratory Abnormalities
Outcome Description
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.
Outcome Time Frame
Up to 4 year 11 months
Outcome Measure
Number of Participants with Clinical Laboratory Abnormalities by Severity
Outcome Description
Number of participants with IRRs will be reported.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Number of Participants Infusion Related Reactions (IRRs)
Outcome Description
Number of participants with IRRs by severity will be reported.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Number of Participants with Infusion Related Reactions (IRRs) by Severity
Outcome Description
The Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.
Outcome Time Frame
Cycle 2 Day 1 (28 days cycle)
Outcome Measure
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
Outcome Description
The Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.
Outcome Time Frame
Cycle 4 Day 1 (28 days cycle)
Outcome Measure
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1
Outcome Description
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.
Outcome Time Frame
From Cycle 4 Day 1 to Cycle 4 Day 15 (28 days cycle)
Outcome Measure
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
Outcome Description
Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies
Outcome Description
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.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)
Outcome Description
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.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Change from Baseline in TASQ as Assessed Over Time
Outcome Description
Participant chair time will be assessed by time and motion analysis.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Participant Chair Time
Outcome Description
Duration of treatment administration will be assessed by time and motion analysis.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Duration of Treatment Administration
Outcome Description
Active health care professional time for drug preparation, treatment administration, and posttreatment monitoring will be assessed by time and motion analysis.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring
Outcome Description
Participant time in treatment room will be assessed by time and motion analysis.
Outcome Time Frame
Up to 1 year 11 months
Outcome Measure
Participant Time in Treatment Room
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404