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NCT Number: NCT05388669

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CEMIC (Centro de Educación Médica e Investigaciones Clínicas), Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lazertinib

Drug

Lazertinib tablets will be administered orally.

Other names: JNJ-73841937, YH25448

Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)

Drug

Amivantamab injection will be administered subcutaneously by manual injection.

Other names: JNJ-61186372

Amivantamab Intravenous

Drug

Amivantamab will be administered by IV infusion.

Other names: JNJ-61186372

Primary outcomes

  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

    Time frame: Pre-dose on Cycle 4 Day 1 (each cycle of 28 days)

    Ctrough was the observed serum concentration of Amivantamab at steady state immediately prior to the next drug administration.

  2. For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab

    Time frame: Pre-dose on Cycle 2 Day 1 (each cycle of 28 days)

    Ctrough was the observed serum concentration of Amivantamab immediately prior to the next drug administration.

  3. Area Under the Concentration (AUC) Time Curve of Amivantamab From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 2

    Time frame: Cycle 2: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hours (hrs) post-dose on Day 1; Arm B: pre-infusion, end of infusion (EOI)+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1

    AUC (Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15 were reported.

Secondary outcomes

  1. Objective Response Rate (ORR)

    Time frame: Up to 3 years 4 months

  2. Progression-Free Survival (PFS)

    Time frame: Up to 3 years 4 months

  3. Duration of Response (DOR)

    Time frame: Up to 3 years 4 months

  4. Time to Response (TTR)

    Time frame: Up to 3 years 4 months

  5. Number of Participants With Adverse Events (AEs)

    Time frame: Up to 3 years 4 months

  6. Number of Participants With AEs by Severity

    Time frame: Up to 3 years 4 months

  7. Number of Participants With Clinical Laboratory Abnormalities

    Time frame: Up to 3 years 4 months

  8. Number of Participants With Clinical Laboratory Abnormalities by Severity

    Time frame: Up to 3 years 4 months

  9. Number of Participants With Infusion Related Reactions (IRRs)

    Time frame: Up to 3 years 4 months

  10. Number of Participants With IRRs by Severity

    Time frame: Up to 3 years 4 months

  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

    Time frame: Pre-dose on Cycle 2 Day 1 (each cycle of 28 days)

  12. For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1

    Time frame: Pre-dose on Cycle 4 Day 1 (each cycle of 28 days)

  13. Model-Predicted Area Under the Concentration Time Curve of Amivantamab at Steady State From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 4

    Time frame: Cycle 4: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hrs post-dose on Day 1; Arm B: preinfusion, EOI+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1

  14. Percentage of Participants With Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies

    Time frame: Up to 3 years 4 months

  15. Percentage of Participants With Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)

    Time frame: Up to 3 years 4 months

  16. Change From Baseline in Therapy Administration Satisfaction Questionnaire (TASQ) as Assessed Over Time

    Time frame: From baseline (Day 1, Cycle 1) to 3 years 4 months (each cycle of 28 days)

  17. Participant Chair Time

    Time frame: Up to 3 years 4 months

  18. Participant Chair Time in Treatment Room

    Time frame: Up to 3 years 4 months

  19. Duration of Treatment Administration

    Time frame: Up to 3 years 4 months

  20. Active Health Care Professional (HCP) Time For Drug Preparation, Treatment Administration and Post-treatment Monitoring

    Time frame: Up to 3 years 4 months

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study 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

Acronym: PALOMA-3

Important dates

Study start
2022
Primary completion
2024
Study completion
2027
First posted
May 24, 2022
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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