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 (PALOMA-3)

• ClinicalTrials.gov Identifier: NCT05388669
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2022
• Last Update Posted: January 31, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: May 19, 2022
• First Posted Date: May 24, 2022
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: August 5, 2022
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2023)

• 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 [ Time Frame: 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.
• For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1 [ Time Frame: 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.
• Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: May 19, 2022)

• Part 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1 [ Time Frame: 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.
• Part 1: Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2 [ Time Frame: 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 Day 1 to Day 15, will be reported will be reported in Cycle 2.
• Part 2: Maximum Serum Concentration (Cmax) of Amivantamab After Cycle 1 Day 1 [ Time Frame: After Cycle 1 Day 1 (28 days cycle) ]
  Cmax is defined as maximum serum concentration of Amivantamab, will be reported after Cycle 1 Day 1.
• Part 2: Area Under the Concentration Time Curve from Day 1 to Day 8 (AUC[Day 1-8]) of Amivantamab of Cycle 1 [ Time Frame: From Cycle 1 Day 1 to Cycle 1 Day 8 (28 days cycle) ]
  AUC(Day 1-8) defined as area under the concentration time curve from Day 1 to Day 8, will be reported in Cycle 1.

Current Secondary Outcome Measures (submitted: December 20, 2023)

• Objective Response Rate (ORR) [ Time Frame: 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).
• Progression-Free Survival (PFS) [ Time Frame: 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.
• Duration of Response (DOR) [ Time Frame: 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.
• Time to Response (TTR) [ Time Frame: 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.
• Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 1 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.
• Number of Participants with AEs by Severity [ Time Frame: Up to 1 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.
• Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 1 year 11 months ]
  Number of participants with clinical laboratory abnormalities (serum Chemistry, hematology, coagulation, and urinalysis) will be reported.
• Number of Participants with Clinical Laboratory Abnormalities by Severity [ Time Frame: Up to 1 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.
• Number of Participants Infusion Related Reactions (IRRs) [ Time Frame: Up to 1 year 11 months ]
  Number of participants with IRRs will be reported.
• Number of Participants with Infusion Related Reactions (IRRs) by Severity [ Time Frame: Up to 1 year 11 months ]
  Number of participants with IRRs by severity will be reported.
• 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 [ Time Frame: 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.
• For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1 [ Time Frame: 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.
• 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 [ Time Frame: 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.
• Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies [ Time Frame: Up to 1 year 11 months ]
  Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.
• Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ) [ Time Frame: 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.
• Change from Baseline in TASQ as Assessed Over Time [ Time Frame: 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.
• Participant Chair Time [ Time Frame: Up to 1 year 11 months ]
  Participant chair time will be assessed by time and motion analysis.
• Duration of Treatment Administration [ Time Frame: Up to 1 year 11 months ]
  Duration of treatment administration will be assessed by time and motion analysis.
• Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring [ Time Frame: 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.
• Participant Time in Treatment Room [ Time Frame: Up to 1 year 11 months ]
  Participant time in treatment room will be assessed by time and motion analysis.

Original Secondary Outcome Measures (submitted: May 19, 2022)

• Part 1 and Part 2: Objective Response Rate (ORR) [ Time Frame: 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).
• Part 1 and Part 2: Progression-Free Survival (PFS) [ Time Frame: 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.
• Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: 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.
• Part 1 and Part 2: Time to Response. [ Time Frame: 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.
• Part 1 and Part 2: Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 1 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.
• Part 1 and Part 2: Number of Participants with AEs by Severity [ Time Frame: Up to 1 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.
• Part 1 and Part 2: Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 1 year 11 months ]
  Number of participants with clinical laboratory abnormalities (serum Chemistry, hematology, coagulation and urinalysis) will be reported.
• Part 1 and Part 2: Number of Participants Infusion Related Reactions (IRRs) [ Time Frame: Up to 1 year 11 months ]
  Number of participants with IRRs will be reported.
• Part 1 and Part 2: Number of Participants with Infusion Related Reactions (IRRs) by Severity [ Time Frame: Up to 1 year 11 months ]
  Number of participants with IRRs by severity will be reported.
• Part 1: Observed Serum Concentration (Ctrough) of Amivantamab on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (28 days cycle) ]
  The Ctrough is the observed serum concentration of Amivantamab on Cycle 2 Day 1 (Part 1 only) immediately prior to the next drug administration.
• Part 1: 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 [ Time Frame: 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 Day 1 to Day 15, will be reported in Cycle 4 (Part 1 only).
• Part 2: Observed Serum Concentration (Ctrough) of Amivantamab on Cycle 4 Day 1 [ Time Frame: Cycle 4 Day 1 (28 days cycle) ]
  Ctrough is the observed serum concentration of Amivantamab on Cycle 4 Day 1 (Part 2 only) immediately prior to the next drug administration.
• Part 1 and Part 2: Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies [ Time Frame: Up to 1 year 11 months ]
  Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.
• Part 1 and Part 2: Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ) [ Time Frame: 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.
• Part 1 and Part 2: Change from Baseline in TASQ as Assessed Over Time [ Time Frame: 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.
• Part 1 and Part 2: Participant Chair Time [ Time Frame: Up to 1 year 11 months ]
  Participant chair time will be assessed by time and motion analysis.
• Part 1 and Part 2: Duration of Treatment Administration [ Time Frame: Up to 1 year 11 months ]
  Duration of treatment administration will be assessed by time and motion analysis.
• Part 1 and Part 2: Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring. [ Time Frame: 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.
• Part 1 and Part 2: Participant Time in Treatment Room [ Time Frame: Up to 1 year 11 months ]
  Participant time in treatment room will be assessed by time and motion analysis.
• Part 1 and Part 2: Rate of Successful Injections with Amivantamab SC-CF OBDS [ Time Frame: Up to 1 year 11 months ]
  Rate of successful injections with amivantamab SC-CF OBDS at each amivantamab SC-CF administration will be reported.
• Part 2: Ease of use and Satisfaction with Amivantamab SC-CF OBDS as Assessed by Ease of use and Satisfaction Questionnaire [ Time Frame: Cycle 2 Day 1 (28 days cycle) ]
  Ease of use and Satisfaction is 8-items questionnaire to access the satisfaction and ease of use of OBDS. The questionnaire is constructed as five-point Likert rating scales. HCPs that cared for participants are asked to rate agreement with the statements, ranging from 1=strongly disagree to 5=strongly agree on Cycle 2 Day 1 (Part 2 only).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Non-small Cell Lung Cancer

Intervention

• Drug: Lazertinib
  Lazertinib tablets will be administered orally.
  Other Names:

  • JNJ-73841937
  • YH25448
• Drug: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)
  Amivantamab injection will be administered subcutaneously by manual injection
  Other Name: JNJ-61186372
• Drug: Amivantamab Intravenous
  Amivantamab will be administered by IV infusion
  Other Name: JNJ-61186372

Study Arms

• Experimental: Arm A: Lazertinib with Amivantamab SC-CF
  Lazertinib 240 mg will be administered orally once daily. Participants will receive Amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 milligrams (mg)/ 2240 mg depending on the body weight by manual injection.
  Interventions:

  • 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.
  Interventions:

  • Drug: Lazertinib
  • Drug: Amivantamab Intravenous

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 7, 2023): 418
• Original Estimated Enrollment (submitted: May 19, 2022): 640
• Estimated Study Completion Date: January 9, 2025
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

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/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Malaysia, Poland, Portugal, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
• Removed Location Countries: India

Administrative Information

• NCT Number: NCT05388669
• Other Study ID Numbers: CR109211; 2022-000525-25 ( EudraCT Number ); 61186372NSC3004 ( Other Identifier: Janssen Research & Development, LLC )
• 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

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: January 2024