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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05388669




Registration number
NCT05388669
Ethics application status
Date submitted
19/05/2022
Date registered
24/05/2022
Date last updated
22/05/2024

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2022-000525-25
Secondary ID [2] 0 0
CR109211
Universal Trial Number (UTN)
Trial acronym
PALOMA-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Lazertinib
Treatment: Drugs - Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)
Treatment: Drugs - Amivantamab Intravenous

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.

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.


Treatment: Drugs: Lazertinib
Lazertinib tablets will be administered orally.

Treatment: Drugs: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)
Amivantamab injection will be administered subcutaneously by manual injection

Treatment: Drugs: Amivantamab Intravenous
Amivantamab will be administered by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Cycle 4 Day 1 (28 days cycle)
Primary outcome [2] 0 0
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1
Timepoint [2] 0 0
Cycle 2 Day 1 (28 days cycle)
Primary outcome [3] 0 0
Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2
Timepoint [3] 0 0
Cycle 2 Day 1 to Cycle 2 Day 15 (28 days cycle)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to 1 year 11 months
Secondary outcome [2] 0 0
Progression-Free Survival (PFS)
Timepoint [2] 0 0
Up to 1 year 11 months
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Up to 1 year 11 months
Secondary outcome [4] 0 0
Time to Response (TTR)
Timepoint [4] 0 0
Up to 1 year 11 months
Secondary outcome [5] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [5] 0 0
Up to 1 year 11 months
Secondary outcome [6] 0 0
Number of Participants with AEs by Severity
Timepoint [6] 0 0
Up to 1 year 11 months
Secondary outcome [7] 0 0
Number of Participants with Clinical Laboratory Abnormalities
Timepoint [7] 0 0
Up to 1 year 11 months
Secondary outcome [8] 0 0
Number of Participants with Clinical Laboratory Abnormalities by Severity
Timepoint [8] 0 0
Up to 1 year 11 months
Secondary outcome [9] 0 0
Number of Participants Infusion Related Reactions (IRRs)
Timepoint [9] 0 0
Up to 1 year 11 months
Secondary outcome [10] 0 0
Number of Participants with Infusion Related Reactions (IRRs) by Severity
Timepoint [10] 0 0
Up to 1 year 11 months
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Cycle 2 Day 1 (28 days cycle)
Secondary outcome [12] 0 0
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1
Timepoint [12] 0 0
Cycle 4 Day 1 (28 days cycle)
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
From Cycle 4 Day 1 to Cycle 4 Day 15 (28 days cycle)
Secondary outcome [14] 0 0
Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies
Timepoint [14] 0 0
Up to 1 year 11 months
Secondary outcome [15] 0 0
Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)
Timepoint [15] 0 0
Up to 1 year 11 months
Secondary outcome [16] 0 0
Change from Baseline in TASQ as Assessed Over Time
Timepoint [16] 0 0
Up to 1 year 11 months
Secondary outcome [17] 0 0
Participant Chair Time
Timepoint [17] 0 0
Up to 1 year 11 months
Secondary outcome [18] 0 0
Duration of Treatment Administration
Timepoint [18] 0 0
Up to 1 year 11 months
Secondary outcome [19] 0 0
Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring
Timepoint [19] 0 0
Up to 1 year 11 months
Secondary outcome [20] 0 0
Participant Time in Treatment Room
Timepoint [20] 0 0
Up to 1 year 11 months

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/01/2025
Actual
Sample size
Target
Accrual to date
Final
418
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
St John of God Hospital Murdoch - Murdoch
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment outside Australia
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California
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Colorado
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Buenos Aires
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Argentina
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Caba
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Argentina
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Ciudad Autonoma de Buenos Aires
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Argentina
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Cordoba
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Argentina
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Viedma
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Barretos
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Belo Horizonte
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Curitiba
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Florianopolis
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Ipatinga
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Pelotas
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Porto Alegre
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Rio de Janeiro
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Salvador
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Santo Andre
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Sao Paulo
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São Paulo
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Canada
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Ontario
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China
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Beijing
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China
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Changchun
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Changzhou
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Chengdu
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Chongqing
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ChongQing
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Ganzhou
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Guang Zhou
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Guangzhou
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China
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Hang Zhou
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Hangzhou
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Harbin
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Huizhou
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Shanghai
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Shen Zhen Shi
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Shenyang
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Shenzhen
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Tianjin
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Wuhan
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XI An
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Xiangyang
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Yantai
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Zhengzhou
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La Tronche
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Lille
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Limoges
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Marseille Cedex 20
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Berlin
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Georgsmarienhütte
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Giessen
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Münster
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Recklinghausen
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Weinsberg
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Haifa
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Jerusalem
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Kfar Saba
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Ramat Gan
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Bari
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Padova
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Ravenna
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Roma
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Rome
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Rozzano
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Chuo Ku
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Himeji
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Hirakata
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Kanagawa
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Kurashiki
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Kurume
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Matsusaka
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Niigata
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Okayama
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Japan
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Osaka
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Japan
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Sapporo-shi
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Japan
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Shizuoka
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Tokyo
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Japan
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Toyoake
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Japan
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Toyonaka-shi
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Japan
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Wakayama
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Japan
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Yamaguchi
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Gyeongsangnam-do
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
State/province [100] 0 0
Seoul
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Malaysia
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Kuala Lumpur
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Malaysia
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Kuching
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Malaysia
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Petaling Jaya
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Poland
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Bydgoszcz
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Krakow
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Otwock
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Poznan
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Warszawa
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Portugal
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Braga
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Portugal
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Lisboa
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Portugal
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Senhora da Hora,
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A Coruna
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Alicante
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Barcelona
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Córdoba
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Spain
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Las Palmas de Gran Canaria
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Lugo
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Spain
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Madrid
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Majadahonda
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Spain
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Málaga
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Oviedo
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Palma de Mallorca
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Sevilla
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Spain
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Valencia
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Taiwan
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Changhua
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Taiwan
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Kaohsiung City
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
Country [129] 0 0
Taiwan
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Tainan
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Taiwan
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Taipei City
Country [131] 0 0
Taiwan
State/province [131] 0 0
Taipei
Country [132] 0 0
Taiwan
State/province [132] 0 0
Taoyuan
Country [133] 0 0
Thailand
State/province [133] 0 0
Bangkok
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Thailand
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Chiangmai
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Istanbul
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Turkey
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Izmir
Country [140] 0 0
Turkey
State/province [140] 0 0
Samsun
Country [141] 0 0
United Kingdom
State/province [141] 0 0
Birmingham
Country [142] 0 0
United Kingdom
State/province [142] 0 0
London
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Newcastle Upon Tyne
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Sutton

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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05388669
Trial related presentations / publications
Public notes

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries