Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT05388669
Ethics application status
Date submitted
19/05/2022
Date registered
24/05/2022
Date last updated
24/10/2024

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 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.

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. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.


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 4 year 11 months
Secondary outcome [6] 0 0
Number of Participants with AEs by Severity
Timepoint [6] 0 0
Up to 4 year 11 months
Secondary outcome [7] 0 0
Number of Participants with Clinical Laboratory Abnormalities
Timepoint [7] 0 0
Up to 4 year 11 months
Secondary outcome [8] 0 0
Number of Participants with Clinical Laboratory Abnormalities by Severity
Timepoint [8] 0 0
Up to 4 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
31/12/2025
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
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
Caba
Country [14] 0 0
Argentina
State/province [14] 0 0
Ciudad Autonoma de Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Cordoba
Country [16] 0 0
Argentina
State/province [16] 0 0
Viedma
Country [17] 0 0
Brazil
State/province [17] 0 0
Barretos
Country [18] 0 0
Brazil
State/province [18] 0 0
Belo Horizonte
Country [19] 0 0
Brazil
State/province [19] 0 0
Curitiba
Country [20] 0 0
Brazil
State/province [20] 0 0
Florianopolis
Country [21] 0 0
Brazil
State/province [21] 0 0
Ipatinga
Country [22] 0 0
Brazil
State/province [22] 0 0
Pelotas
Country [23] 0 0
Brazil
State/province [23] 0 0
Porto Alegre
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio de Janeiro
Country [25] 0 0
Brazil
State/province [25] 0 0
Salvador
Country [26] 0 0
Brazil
State/province [26] 0 0
Santo Andre
Country [27] 0 0
Brazil
State/province [27] 0 0
Sao Paulo
Country [28] 0 0
Brazil
State/province [28] 0 0
São Paulo
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
China
State/province [30] 0 0
Beijing
Country [31] 0 0
China
State/province [31] 0 0
Changchun
Country [32] 0 0
China
State/province [32] 0 0
Changzhou
Country [33] 0 0
China
State/province [33] 0 0
Chengdu
Country [34] 0 0
China
State/province [34] 0 0
Chongqing
Country [35] 0 0
China
State/province [35] 0 0
ChongQing
Country [36] 0 0
China
State/province [36] 0 0
Ganzhou
Country [37] 0 0
China
State/province [37] 0 0
Guang Zhou
Country [38] 0 0
China
State/province [38] 0 0
Guangzhou
Country [39] 0 0
China
State/province [39] 0 0
Hang Zhou
Country [40] 0 0
China
State/province [40] 0 0
Hangzhou
Country [41] 0 0
China
State/province [41] 0 0
Harbin
Country [42] 0 0
China
State/province [42] 0 0
Huizhou
Country [43] 0 0
China
State/province [43] 0 0
Liuzhou
Country [44] 0 0
China
State/province [44] 0 0
Nanchong
Country [45] 0 0
China
State/province [45] 0 0
Shanghai
Country [46] 0 0
China
State/province [46] 0 0
Shen Zhen Shi
Country [47] 0 0
China
State/province [47] 0 0
Shenyang
Country [48] 0 0
China
State/province [48] 0 0
Shenzhen
Country [49] 0 0
China
State/province [49] 0 0
Tianjin
Country [50] 0 0
China
State/province [50] 0 0
Wuhan
Country [51] 0 0
China
State/province [51] 0 0
XI An
Country [52] 0 0
China
State/province [52] 0 0
Xiangyang
Country [53] 0 0
China
State/province [53] 0 0
Yantai
Country [54] 0 0
China
State/province [54] 0 0
Zhengzhou
Country [55] 0 0
France
State/province [55] 0 0
La Tronche
Country [56] 0 0
France
State/province [56] 0 0
Lille
Country [57] 0 0
France
State/province [57] 0 0
Limoges
Country [58] 0 0
France
State/province [58] 0 0
Marseille Cedex 20
Country [59] 0 0
Germany
State/province [59] 0 0
Berlin
Country [60] 0 0
Germany
State/province [60] 0 0
Georgsmarienhütte
Country [61] 0 0
Germany
State/province [61] 0 0
Giessen
Country [62] 0 0
Germany
State/province [62] 0 0
Münster
Country [63] 0 0
Germany
State/province [63] 0 0
Recklinghausen
Country [64] 0 0
Germany
State/province [64] 0 0
Weinsberg
Country [65] 0 0
Israel
State/province [65] 0 0
Haifa
Country [66] 0 0
Israel
State/province [66] 0 0
Jerusalem
Country [67] 0 0
Israel
State/province [67] 0 0
Kfar Saba
Country [68] 0 0
Israel
State/province [68] 0 0
Petah-Tikva
Country [69] 0 0
Israel
State/province [69] 0 0
Ramat Gan
Country [70] 0 0
Italy
State/province [70] 0 0
Bari
Country [71] 0 0
Italy
State/province [71] 0 0
Bologna
Country [72] 0 0
Italy
State/province [72] 0 0
Milano
Country [73] 0 0
Italy
State/province [73] 0 0
Orbassano
Country [74] 0 0
Italy
State/province [74] 0 0
Padova
Country [75] 0 0
Italy
State/province [75] 0 0
Ravenna
Country [76] 0 0
Italy
State/province [76] 0 0
Roma
Country [77] 0 0
Italy
State/province [77] 0 0
Rome
Country [78] 0 0
Italy
State/province [78] 0 0
Rozzano
Country [79] 0 0
Japan
State/province [79] 0 0
Chuo Ku
Country [80] 0 0
Japan
State/province [80] 0 0
Himeji
Country [81] 0 0
Japan
State/province [81] 0 0
Hirakata
Country [82] 0 0
Japan
State/province [82] 0 0
Kanagawa
Country [83] 0 0
Japan
State/province [83] 0 0
Kurashiki
Country [84] 0 0
Japan
State/province [84] 0 0
Kurume
Country [85] 0 0
Japan
State/province [85] 0 0
Matsusaka
Country [86] 0 0
Japan
State/province [86] 0 0
Niigata
Country [87] 0 0
Japan
State/province [87] 0 0
Okayama
Country [88] 0 0
Japan
State/province [88] 0 0
Osaka City
Country [89] 0 0
Japan
State/province [89] 0 0
Sapporo-shi
Country [90] 0 0
Japan
State/province [90] 0 0
Shizuoka
Country [91] 0 0
Japan
State/province [91] 0 0
Tokyo
Country [92] 0 0
Japan
State/province [92] 0 0
Toyoake
Country [93] 0 0
Japan
State/province [93] 0 0
Toyonaka-shi
Country [94] 0 0
Japan
State/province [94] 0 0
Wakayama
Country [95] 0 0
Japan
State/province [95] 0 0
Yamaguchi
Country [96] 0 0
Korea, Republic of
State/province [96] 0 0
Gyeonggi-do
Country [97] 0 0
Korea, Republic of
State/province [97] 0 0
Gyeongsangnam-do
Country [98] 0 0
Korea, Republic of
State/province [98] 0 0
Jeollanam-do
Country [99] 0 0
Korea, Republic of
State/province [99] 0 0
Seongnam-si
Country [100] 0 0
Korea, Republic of
State/province [100] 0 0
Seoul
Country [101] 0 0
Malaysia
State/province [101] 0 0
Kuala Lumpur
Country [102] 0 0
Malaysia
State/province [102] 0 0
Kuching
Country [103] 0 0
Malaysia
State/province [103] 0 0
Petaling Jaya
Country [104] 0 0
Poland
State/province [104] 0 0
Bydgoszcz
Country [105] 0 0
Poland
State/province [105] 0 0
Krakow
Country [106] 0 0
Poland
State/province [106] 0 0
Otwock
Country [107] 0 0
Poland
State/province [107] 0 0
Poznan
Country [108] 0 0
Poland
State/province [108] 0 0
Warszawa
Country [109] 0 0
Portugal
State/province [109] 0 0
Braga
Country [110] 0 0
Portugal
State/province [110] 0 0
Lisboa
Country [111] 0 0
Portugal
State/province [111] 0 0
Senhora da Hora,
Country [112] 0 0
Spain
State/province [112] 0 0
A Coruna
Country [113] 0 0
Spain
State/province [113] 0 0
Alicante
Country [114] 0 0
Spain
State/province [114] 0 0
Barcelona
Country [115] 0 0
Spain
State/province [115] 0 0
Córdoba
Country [116] 0 0
Spain
State/province [116] 0 0
Las Palmas de Gran Canaria
Country [117] 0 0
Spain
State/province [117] 0 0
Lugo
Country [118] 0 0
Spain
State/province [118] 0 0
Madrid
Country [119] 0 0
Spain
State/province [119] 0 0
Majadahonda
Country [120] 0 0
Spain
State/province [120] 0 0
Málaga
Country [121] 0 0
Spain
State/province [121] 0 0
Oviedo
Country [122] 0 0
Spain
State/province [122] 0 0
Palma de Mallorca
Country [123] 0 0
Spain
State/province [123] 0 0
Sevilla
Country [124] 0 0
Spain
State/province [124] 0 0
Valencia
Country [125] 0 0
Taiwan
State/province [125] 0 0
Changhua
Country [126] 0 0
Taiwan
State/province [126] 0 0
Kaohsiung City
Country [127] 0 0
Taiwan
State/province [127] 0 0
Kaohsiung
Country [128] 0 0
Taiwan
State/province [128] 0 0
Taichung
Country [129] 0 0
Taiwan
State/province [129] 0 0
Tainan
Country [130] 0 0
Taiwan
State/province [130] 0 0
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
Country [134] 0 0
Thailand
State/province [134] 0 0
Chiangmai
Country [135] 0 0
Turkey
State/province [135] 0 0
Adana
Country [136] 0 0
Turkey
State/province [136] 0 0
Ankara
Country [137] 0 0
Turkey
State/province [137] 0 0
Edirne
Country [138] 0 0
Turkey
State/province [138] 0 0
Istanbul
Country [139] 0 0
Turkey
State/province [139] 0 0
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/study/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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05388669