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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/NCT04077463




Registration number
NCT04077463
Ethics application status
Date submitted
30/08/2019
Date registered
4/09/2019
Date last updated
8/11/2023

Titles & IDs
Public title
A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
Scientific title
An Open-label Phase 1/1b Study to Evaluate the Safety and Pharmacokinetics of JNJ-73841937 (Lazertinib), a Third Generation EGFR-TKI, as Monotherapy or in Combinations With JNJ-61186372, a Human Bispecific EGFR and cMet Antibody in Participants With Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
73841937NSC1001
Secondary ID [2] 0 0
CR108656
Universal Trial Number (UTN)
Trial acronym
Chrysalis-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

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

Experimental: Phase 1 (monotherapy dose escalation): Lazertinib - Participants will receive Lazertinib monotherapy orally once daily (QD) in 21-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. The subsequent doses of Lazertinib will be assigned by the Study Evaluation Team (SET) according to the dose escalation strategy by Bayesian logistic regression model (BLRM).

Experimental: Phase 1b (combination): Lazertinib and Amivantamab - Participants will receive Lazertinib and Amivantamab, after the safety of RP2D of Lazertinib is confirmed in the Phase 1, in 28-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. This phase will start enrolling participants after the safety of Amivantamab is confirmed in Japanese participants in Study 61186372EDI1001 (NCT02609776).

Experimental: Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP) - Participants will receive Lazertinib starting dose administered orally once daily (QD) in combination with Amivantamab, and doses of platinum-based chemotherapy (carboplatin and pemetrexed) per standard of care according to local guidance in a 21-day cycle for 4 cycles followed by maintenance with Lazertinib, Amivantamab and pemetrexed until disease progression or unacceptable toxicities.

Experimental: Phase 1b (expansion) Cohort A: Lazertinib and Amivantamab - This cohort A will further characterize the safety, tolerability, and preliminary antitumor activity of Lazertinib and Amivantamab based combinations within specific NSCLC population "who have progressed after osimertinib and subsequent platinum-based chemotherapy, and platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR TKI is allowed if administered prior to osimertinib. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Experimental: Phase 1b (expansion) Cohort B: Lazertinib and Amivantamab - This Cohort B will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants previously treated with advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Experimental: Phase 1b (expansion) Cohort C: Lazertinib and Amivantamab - This Cohort C will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants with uncommon EGFR mutations. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Experimental: Phase 1b (expansion) Cohort D: Lazertinib and Amivantamab - Cohort D will seek to validate one or both potential biomarker strategies (next generation sequencing [NGS] and Immunohistochemical [IHC]), previously identified in Cohort E of Study 61186372EDI1001, in participants with osimertinib-relapsed, but chemotherapy-naive, EGFR Exon19del or L858R mutated NSCLC. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Experimental: Phase 1b (expansion) Cohort E: Lazertinib and Amivantamab - Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. Cohort E will seek to validate the immunohistochemical (IHC)-based biomarker strategy, by characterizing the activity of Amivantamab and Lazertinib combination in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC. In addition, Cohort E will seek to collect prospective data to confirm that prophylactic anticoagulation safely and effectively decreases the incidence of VTE events for patients treated with the combination of Amivantamab and Lazertinib, using Cohort F as reference.

Experimental: Phase 1b (expansion) Cohort F: Amivantamab Monotherapy - Participants will receive Amivantamab monotherapy once weekly (QW) for 4 weeks, then every 2 weeks thereafter. Cohort F will seek to validate the IHC-based biomarker strategy, previously identified in Cohort D, by characterizing the activity of JNJ-61186372 monotherapy (Cohort F) in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC.


Treatment: Drugs: Lazertinib
Lazertinib will be administered orally.

Treatment: Drugs: Amivantamab
Amivantamab will be administered as an intravenous (IV) infusion.

Treatment: Drugs: Carboplatin
Carboplatin will be administered as IV infusion.

Treatment: Drugs: Pemetrexed
Pemetrexed will be administered as IV infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1)
Timepoint [1] 0 0
Until the end of first cycle (21 days for Phase 1)
Primary outcome [2] 0 0
Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b)
Timepoint [2] 0 0
Until the end of first cycle (28 days for Phase 1b)
Primary outcome [3] 0 0
Overall Response Rate (ORR) (Phase 1b Expansion Cohorts A-D)
Timepoint [3] 0 0
Up to 2.5 years
Primary outcome [4] 0 0
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion Cohorts A-E)
Timepoint [4] 0 0
Up to 2.5 years
Primary outcome [5] 0 0
Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP])
Timepoint [5] 0 0
Until the end of first cycle (21 days for Phase 1b combination LACP)
Primary outcome [6] 0 0
Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP)
Timepoint [6] 0 0
Up to 2.5 years
Primary outcome [7] 0 0
Overall Response Rate (ORR) per RECIST version 1.1 (v1.1) with NGS Analysis of Circulating Tumor ctDNA, IHC Analysis of EGFR and MET Expression (Phase 1b Expansion Cohort D)
Timepoint [7] 0 0
Up to 2.5 years
Primary outcome [8] 0 0
ORR Among Participants with MET3+ Staining on Greater Than or Equal to (>=)25 Percent (%) of Tumor Cells (Phase 1b Expansion Cohorts E and F)
Timepoint [8] 0 0
Up to 2.5 years
Primary outcome [9] 0 0
Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
Timepoint [9] 0 0
Up to 2.5 years
Primary outcome [10] 0 0
Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
Timepoint [10] 0 0
Up to 2.5 years
Secondary outcome [1] 0 0
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1 and Phase 1b)
Timepoint [1] 0 0
Up to 2.5 years
Secondary outcome [2] 0 0
Plasma Concentration of Lazertinib (Phase 1 and Phase 1b)
Timepoint [2] 0 0
Up to End of Treatment [EOT]) (30 days after last dose) (up to 2.5 years)
Secondary outcome [3] 0 0
Serum Concentration of Amivantamab (Phase 1b)
Timepoint [3] 0 0
Up to EOT (30 days after last dose) (up to 2.5 years)
Secondary outcome [4] 0 0
Number of Participants with Anti-drug Antibodies Against Amivantamab (Phase 1b)
Timepoint [4] 0 0
Up to EOT (30 days after last dose) (up to 2.5 years)
Secondary outcome [5] 0 0
Progression free survival (PFS) (Phase 1b Expansion)
Timepoint [5] 0 0
Up to 2.5 years
Secondary outcome [6] 0 0
Time to Treatment Failure (TTF) (Phase 1b Expansion)
Timepoint [6] 0 0
Up to 2.5 years
Secondary outcome [7] 0 0
Overall Survival (OS) (Phase 1b Expansion)
Timepoint [7] 0 0
Up to 2.5 years
Secondary outcome [8] 0 0
Duration of Response (DOR) (Phase 1b expansion)
Timepoint [8] 0 0
Up to 2.5 years
Secondary outcome [9] 0 0
Clinical Benefit Rate (CBR) (Phase 1b expansion)
Timepoint [9] 0 0
Up to 2.5 years
Secondary outcome [10] 0 0
Number of Participants with Venous Thromboembolic (VTE) Events by Severity
Timepoint [10] 0 0
Up to 2.5 years
Secondary outcome [11] 0 0
Number of Participants with Adverse Events (AEs) (Phase 1b Expansion Cohort F)
Timepoint [11] 0 0
Up to 2.5 years
Secondary outcome [12] 0 0
ORR (Phase 1b expansion Cohorts E and F)
Timepoint [12] 0 0
Up to 2.5 years
Secondary outcome [13] 0 0
DOR (Phase 1b Expansion Cohorts E and F)
Timepoint [13] 0 0
Up to 2.5 years
Secondary outcome [14] 0 0
CBR (Phase 1b expansion Cohorts E and F)
Timepoint [14] 0 0
Up to 2.5 years
Secondary outcome [15] 0 0
Intracranial Progression free survival (PFS) (Phase 1b Expansion E and F)
Timepoint [15] 0 0
Up to 2.5 years

Eligibility
Key inclusion criteria
- Phase 1 and Phase 1b lazertinib+Amivantamab combination cohorts: Histologically or
cytologically confirmed non-small cell lung cancer (NSCLC) with previously epidermal
growth factor receptor (EGFR) mutation (identified locally in a Clinical Laboratory
Improvement Amendments [CLIA]-certified laboratory [or equivalent]) that is metastatic
or unresectable, and have progressed after standard of care front-line therapy, and
exhausted available options with targeted therapy. A participant who has refused all
other currently available therapeutic options is allowed to enroll

- For the Phase 1b Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)
combination cohort: histologically or cytologically confirmed advanced or metastatic
EGFR-mutated NSCLC who have progressed on or after an EGFR-TKI as the most recent line
of treatment with a maximum of 3 prior lines of therapy in the metastatic setting
allowed

- For all expansion cohorts, the EGFR mutation must have been previously histologically
or cytologically characterized, as performed by a CLIA-certified (US sites) or an
accredited (outside of US) local laboratory, with a copy of the mutation analysis
being submitted during screening (Phase 1b expansion Cohort B, C, D, E, and F)

1. Expansion Cohort A: Participant must have advanced or metastatic EGFR-mutated
non-small cell lung cancer (NSCLC) that has progressed on prior treatment with
osimertinib in the first or second line, followed by progression on a
platinum-based chemotherapy regimen as the last line of therapy prior to study
enrollment. Prior use of first or second generation EGFR tyrosine kinase
inhibitor (TKI) is allowed if administered prior to osimertinib

2. Expansion Cohort B: Participant must have previously treated, advanced or
metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation.
Participants should have been treated with standard of care, platinum-based
chemotherapy regimens, but may have treated with approved EGFR TKI,
investigational EGFR, or immunotherapy agents if refusing front line
platinum-based chemotherapy standard of care. Up to 3 lines of prior systemic
anti-cancer treatment are allowed

3. Expansion Cohort C: Participant must have advanced or metastatic NSCLC
characterized by an uncommon activating mutation Additional uncommon EGFR
mutations/alterations, beyond those listed above, may be considered for
enrollment after agreement with the medical monitor. Participants may be
treatment naïve or have been treated with one prior line of therapy which must be
a first or second generation TKI (that is gefitinib, erlotinib, afatinib) in the
most recent line of therapy. Prior chemotherapy is allowed if administered prior
to EGFR TKI therapy, or as the only systemic anti-cancer therapy prior to study
enrollment. Up to 2 lines of prior systemic anti-cancer treatment are allowed

4. Expansion Cohort D, E, and F: Participant must have advanced or metastatic
EGFR-mutated NSCLC (EGFR Exon19 deletion or L858R) that has progressed on prior
treatment with osimertinib in the first or second line (after first- or
second-generation EGFR TKI), as the immediate prior line of therapy. Only
previous treatment in the metastatic setting with a first, second, or third
generation EGFR TKI is allowed. In addition, participants considered for Cohorts
E and F 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 (from Day 1 through Day 120) according to
national comprehensive cancer network (NCCN) or local guidelines, if assigned to
the combination Cohort E

- Evaluable disease

- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

- Participants must meet the study protocol defined laboratory criteria without having a
history of red blood cell transfusion, platelet transfusion, or granulocyte-colony
stimulating factor support within 7 days prior to the date of the test

- A woman of childbearing potential: Must have a negative serum beta human chorionic
gonadotropin at screening; Must agree not to breast-feed during the study and for 6
months after the last dose of study intervention. (Enrollment is not allowed even if a
woman who is breast-feeding stops breast-feeding); Must agree not to donate eggs (ova,
oocytes) for the purposes of assisted reproduction during the study and for 6 months
after receiving the last dose of study intervention
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant has an uncontrolled illness, including but not limited to uncontrolled
diabetes, ongoing or active infection (includes infection requiring treatment with
antimicrobial therapy [participants will be required to complete antibiotics 1 week
prior to study treatment] or diagnosed or suspected viral infection); active bleeding
diathesis; Impaired oxygenation requiring continuous oxygen supplementation;
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the formulated product, or previous significant bowel resection that would
preclude adequate absorption of study treatment; or psychiatric illness or any other
circumstances (including social circumstances) that would limit compliance with study
requirements. Any ophthalmologic condition that is either clinically unstable or
requires treatment

- Prior treatment with anti programmed cell death-1 (PD-1) or anti programmed cell
death-ligand 1 (PD-L1) antibody within 6 weeks of planned first dose of study
intervention

- Untreated brain or other central nervous system (CNS) metastases whether symptomatic
or asymptomatic. Participants who have completed definitive therapy, are not on
steroids, and have a stable clinical status for at least 2 weeks prior to study
treatment may be eligible for Phase 1b expansion cohorts. If brain metastases are
diagnosed on Screening imaging, the participant may be enrolled, or rescreened for
eligibility, after definitive treatment if above criteria are met

- 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 <=2 peripheral neuropathy, and Grade <=2 hypothyroidism
stable on hormone replacement therapy)

- Allergies, hypersensitivity, or intolerance to Lazertinib or JNJ-61186372 or their
excipients. For the LACP combination cohort: participant has a contraindication for
the use of carboplatin or pemetrexed (refer to local prescribing information for each
agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12
or folic acid

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
Other
Other design features
Phase
Phase 1
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
4/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/02/2027
Actual
Sample size
Target
460
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
China
State/province [13] 0 0
Changchun
Country [14] 0 0
China
State/province [14] 0 0
Changsha
Country [15] 0 0
China
State/province [15] 0 0
Chengdu
Country [16] 0 0
China
State/province [16] 0 0
Chongqing
Country [17] 0 0
China
State/province [17] 0 0
Guangzhou
Country [18] 0 0
China
State/province [18] 0 0
Hang Zhou
Country [19] 0 0
China
State/province [19] 0 0
Jinan
Country [20] 0 0
China
State/province [20] 0 0
Kunming
Country [21] 0 0
China
State/province [21] 0 0
Shanghai
Country [22] 0 0
China
State/province [22] 0 0
Shenyang
Country [23] 0 0
China
State/province [23] 0 0
Tianjin
Country [24] 0 0
China
State/province [24] 0 0
Wuhan
Country [25] 0 0
China
State/province [25] 0 0
Xi'an
Country [26] 0 0
France
State/province [26] 0 0
Bordeaux
Country [27] 0 0
France
State/province [27] 0 0
Lyon Cedex 8
Country [28] 0 0
France
State/province [28] 0 0
Marseille
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Poitiers
Country [31] 0 0
France
State/province [31] 0 0
Saint Mande
Country [32] 0 0
France
State/province [32] 0 0
Villejuif Cedex
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Essen
Country [35] 0 0
Germany
State/province [35] 0 0
Frankfurt am Main
Country [36] 0 0
Germany
State/province [36] 0 0
Gauting
Country [37] 0 0
Germany
State/province [37] 0 0
Halle (Saale)
Country [38] 0 0
Germany
State/province [38] 0 0
Hemer
Country [39] 0 0
Germany
State/province [39] 0 0
Köln
Country [40] 0 0
Germany
State/province [40] 0 0
Oldenburg
Country [41] 0 0
Germany
State/province [41] 0 0
Stuttgart
Country [42] 0 0
Italy
State/province [42] 0 0
Milano
Country [43] 0 0
Italy
State/province [43] 0 0
Monza
Country [44] 0 0
Italy
State/province [44] 0 0
Napoli
Country [45] 0 0
Italy
State/province [45] 0 0
Ravenna
Country [46] 0 0
Japan
State/province [46] 0 0
Chuo-Ku
Country [47] 0 0
Japan
State/province [47] 0 0
Hirakata
Country [48] 0 0
Japan
State/province [48] 0 0
Hyogo
Country [49] 0 0
Japan
State/province [49] 0 0
Kashiwa
Country [50] 0 0
Japan
State/province [50] 0 0
Nagoya-Shi
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Shizuoka
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Gyeonggi-do
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seoul
Country [55] 0 0
Puerto Rico
State/province [55] 0 0
Rio Piedras
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Spain
State/province [58] 0 0
Seville
Country [59] 0 0
Taiwan
State/province [59] 0 0
Kaohsiung
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taichung
Country [61] 0 0
Taiwan
State/province [61] 0 0
Tainan
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei City

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/ct2/show/NCT04077463