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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05498428




Registration number
NCT05498428
Ethics application status
Date submitted
10/08/2022
Date registered
12/08/2022
Date last updated
14/08/2024

Titles & IDs
Public title
A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
Scientific title
A Phase 2, Open-Label, Parallel Cohort Study of Subcutaneous Amivantamab in Multiple Regimens in Patients With Advanced or Metastatic Solid Tumors Including EGFR-mutated Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
2022-000526-21
Secondary ID [2] 0 0
CR109264
Universal Trial Number (UTN)
Trial acronym
PALOMA-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-small-Cell Lung 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Amivantamab

Experimental: Cohort 1(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q2W) + Lazertinib - Participants with treatment-naive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 19 deletion (exon19del) or exon 21 leucine 858 to arginine substitution (exon 21 L858R) mutation, will receive amivantamab SC-CF injection, 1600 milligrams (mg) or 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily.

Experimental: Cohort 2(Exon20 NSCLC,1L, Previously Untreated): Amivantamab (Q3W) + Chemotherapy - Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR exon20ins mutation will receive Amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m\^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles.

Experimental: Cohort 3(Exon19del/Exon21 L858R NSCLC,2L,Post Osimertinib):Amivantamab(Q3W)+Lazertinib+Chemotherapy - Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Lazertinib 240 mg orally once daily starting Cycle 5 Day 1 when carboplatin is complete or sooner if carboplatin discontinued earlier than Cycle 4.

Experimental: Cohort 3b(Exon19del/Exon21 L858R NSCLC, 2L, Post Osimertinib): Amivantamab (Q3W)+Chemotherapy - Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.

Experimental: Cohort 4(Previously Treated with Amivantamab IV): Switch from Amivantamab IV to SC-CF (Q2W) - Participants who were previously on amivantamab IV once every 2 weeks (Q2W) regimen as part of standard of care, for at least 8 weeks, either as monotherapy or combination with lazertinib, will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg.

Experimental: Cohort 5(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q4W) + Lazertinib - Participants with treatment-naïve locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation will receive amivantamab SC-CF induction with 1,600 mg (or 2,240 mg if BW \>=80 kg) on Cycle 1 Days 1, 8, 15, and 22, starting with Cycle 2 on Day 1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3,520 mg (or 4,640 mg if BW \>=80 kg); along with lazertinib 240 mg by mouth once daily from Cycle 1 Day 1.

Experimental: Cohort6(Exon19del/Exon21L858R,NSCLC1L,PreviouslyUntreated):Amivantamab(Q2W)+Lazertinib+Anticoagulant - Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation treated will receive will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily from Cycle 1 Day 1. Participants will additionally take prophylactic anticoagulation with a direct oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH) for the first four months of study treatment (from Day 1 through Day 120) with the combination of amivantamab and lazertinib.

Experimental: Cohort 7(Exon19del/Exon21 L858R NSCLC,2L,Post Amivantamab+Lazertinib):Amivantamab(Q3W)+Chemotherapy - Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after the combination of amivantamab and lazertinib will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.


Treatment: Drugs: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
* Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC) that is not amenable to curative therapy including surgical resection or chemoradiation. Additional Cohort specific disease requirements include: Cohorts 1, 3, 3b, 5, 6 and 7: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or Exon 21 L858R mutation; Cohort 2: EGFR Exon 20ins mutation. Cohorts 1,5,and6: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohort 2: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohorts 3and3b: Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second-line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Cohort 4: Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. Cohort 7: Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded. EGFR mutation must have been identified as determined by 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 states [US]) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor
* All cohorts except Cohort 4: Participants must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy
* May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions
* Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1
* Cohort 6: Must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of study treatment
* A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis
* Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
* Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary
* For all cohorts (with regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1
* Other clinically active liver disease of infectious origin
* Participant has a history of clinically significant cardiovascular disease including, but not limited to: a) All cohorts: diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary; b) All cohorts (with regimens potentially including lazertinib): Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden); c) All cohorts (with regimens potentially including lazertinib): Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines; d) prolonged corrected QT interval by Fridericia (QTcF) interval greater than (>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); e) uncontrolled (persistent) hypertension: systolic blood pressure >160 millimeter(s) of mercury (mmHg); diastolic blood pressure >100 mmHg; f) Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association [NYHA] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1); g) pericarditis/clinically significant pericardial effusion; h) myocarditis; i) baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan
* Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to [<=] 10 milligrams per day [mg/day] prednisone or equivalent) for at least 2 weeks prior to treatment allocation

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/08/2026
Actual
Sample size
Target
390
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation \[SC-CF\]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).
Trial website
https://clinicaltrials.gov/study/NCT05498428
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05498428