We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Lazertinib and Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05388669
Recruitment Status : Recruiting
First Posted : May 24, 2022
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Non-small Cell Lung Cancer Drug: Lazertinib Drug: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF) Drug: Amivantamab Intravenous Device: Amivantamab SC-CF On-Body Delivery System (OBDS) Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Detailed Description:
Lung cancer is one of the most common types of cancer and is the most common cause of death from cancer. Amivantamab is a low-fucose, fully human immunoglobulin (IgG)1-based bispecific antibody directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine kinase receptors. Lazertinib is an oral, highly potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The study will include screening phase (up to 28 days), a treatment phase (from randomization until the end of treatment visit), and a follow-up phase for both parts (from end of treatment visit until the end of study, death, lost to follow-up, or withdrawal of consent, whichever comes first). Safety will be assessed by physical examinations, vital signs, electrocardiograms, echocardiograms, ophthalmologic assessments, laboratory tests, adverse event (AE) frequency and severity (by Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) monitoring, and concomitant medication use. The total duration of the study will be up to 1 year and 11 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Administered Via Manual Injection Compared With Intravenous Amivantamab or Amivantamab Subcutaneous On Body Delivery System in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy
Actual Study Start Date : August 5, 2022
Estimated Primary Completion Date : January 24, 2024
Estimated Study Completion Date : August 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Amivantamab

Arm Intervention/treatment
Experimental: Part 1: Arm A1: 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.
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

Experimental: Part 1: Arm B1: 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.
Drug: Lazertinib
Lazertinib tablets will be administered orally.
Other Names:
  • JNJ-73841937
  • YH25448

Drug: Amivantamab Intravenous
Amivantamab will be administered by IV infusion
Other Name: JNJ-61186372

Experimental: Part 2: Arm A2: Lazertinib with Amivantamab SC-CF
Lazertinib 240 mg will be administered orally once daily. Participants will receive amivantamab SC-CF, 1600 mg or 2240 depending on the body weight mg by manual injection.
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

Experimental: Part B2: Arm B2: Lazertinib with Amivantamab SC-CF OBDS
Lazertinib 240 mg will be administered orally once daily. Participants will receive amivantamab SC-CF On-Body Delivery System (OBDS), 1600 mg or 2240 mg depending on the body weight by manual injection.
Drug: Lazertinib
Lazertinib tablets will be administered orally.
Other Names:
  • JNJ-73841937
  • YH25448

Device: Amivantamab SC-CF On-Body Delivery System (OBDS)
Amivantamab will be administered by subcutaneously by OBDS
Other Name: JNJ-61186372




Primary Outcome Measures :
  1. Part 1 - For All Regions Other Than the European Union (EU): 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.

  2. Part 1 - For EU Only: 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Part 1 and Part 2: 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.

  9. 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.

  10. 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.

  11. Part 1 - For Regions Other Than EU: 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 Amivantamaba at pre-dose on Cycle 2 Day 1 (Part 1 only) immediately prior to the next drug administration.

  12. Part 1 - For EU Only: 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 (Part 1 only) immediately prior to the next drug administration.

  13. 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).

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05388669


Contacts
Layout table for location contacts
Contact: Study Contact 844-434-4210 Participate-In-This-Study@its.jnj.com

Locations
Show Show 198 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT05388669    
Other Study ID Numbers: CR109211
2022-000525-25 ( EudraCT Number )
61186372NSC3004 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: May 24, 2022    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Amivantamab-vmjw
Lazertinib
Antibodies, Bispecific
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs