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JOURNAL ONKOLOGIE – STUDIE

A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer

Rekrutierend

NCT-Nummer:
NCT04077463

Studienbeginn:
September 2019

Letztes Update:
01.04.2021

Wirkstoff:
Lazertinib, Amivantamab, Carboplatin, Pemetrexed

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC

Kontakt

Studienlocations
(3 von 80)

Evangelische Lungenklinik Berlin
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Essen
45147 Essen
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Klinikum der Johann Wolfgang Goethe-Universität
60590 Frankfurt am Main
(Hessen)
GermanyNoch nicht rekrutierend» Google-Maps
Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken München-Gauting
82131 Gauting
(Bayern)
GermanyRekrutierend» Google-Maps
Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
06120 Halle (Saale)
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Thoraxklinik am Universitätsklinikum Heidelberg
69126 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Lungenklinik Hemer
58675 Hemer
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Lungenkrebszentrum Uniklinik Köln / Solingen
Kerpener Straße 62
50937 Köln
DeutschlandNoch nicht rekrutierend» Google-Maps
Kliniiken der Stadt Köln gGmbH, Krankenhaus Köln-Mehrheim
51109 Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Pius-Hospital Oldenburg
26121 Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Robert-Bosch-Krankenhaus - Klinik Schillerhoehe
70376 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
USC - Norris Comprehensive Cancer Center
90089-9173 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
University of California, Irvine
92868 Orange
United StatesNoch nicht rekrutierend» Google-Maps
UCSF Helen Diller Comprehensive
94158 San Francisco
United StatesNoch nicht rekrutierend» Google-Maps
Stanford University Medical Center
94305 Stanford
United StatesRekrutierend» Google-Maps
Cedars Sinai Medical Center
90048 West Hollywood
United StatesNoch nicht rekrutierend» Google-Maps
H. Lee Moffitt Cancer & Research Institute
33612 Tampa
United StatesNoch nicht rekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesNoch nicht rekrutierend» Google-Maps
Boston University Medical Center
02118 Boston
United StatesRekrutierend» Google-Maps
Dana Farber Cancer Institute
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps
Barbara Ann Karmanos Cancer Institute
48201 Detroit
United StatesRekrutierend» Google-Maps
Washington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Langone Health at NYC University, NYU School of Medicine
10016 New York
United StatesRekrutierend» Google-Maps
Columbia University Medical Center
10032 New York
United StatesRekrutierend» Google-Maps
Providence Portland Medical Center
97213 Portland
United StatesRekrutierend» Google-Maps
University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Huntsman Cancer Institute
84112 Salt Lake City
United StatesNoch nicht rekrutierend» Google-Maps
Virginia Cancer Specialists
22031 Fairfax
United StatesRekrutierend» Google-Maps
University of Washington
98109 Seattle
United StatesNoch nicht rekrutierend» Google-Maps
Beijing Cancer Hospital
100142 Beijing
ChinaNoch nicht rekrutierend» Google-Maps
The First Bethune Hospital of Jilin University
130021 Changchun
ChinaRekrutierend» Google-Maps
Hunan Cancer hospital
410013 Changsha
ChinaNoch nicht rekrutierend» Google-Maps
West China School of Medicine/West China Hospital, Sichuan University
610041 Chengdu
ChinaRekrutierend» Google-Maps
The Fifth Affiliated Hospital of Guangzhou Medical University
440112 Guangzhou
ChinaRekrutierend» Google-Maps
The First Affiliated Hospital of NanChang University
330006 Nanchang
ChinaNoch nicht rekrutierend» Google-Maps
Shengjing Hospital of China Medical University
110022 Shenyang
ChinaRekrutierend» Google-Maps
Tianjin Medical University Cancer Institute and Hospital
300000 Tianjin
ChinaRekrutierend» Google-Maps
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
430022 Wuhan
ChinaRekrutierend» Google-Maps
First Affiliated Hospital, Xi'an Jiaotong University
710061 Xi'an
ChinaRekrutierend» Google-Maps
Institut Gustave Roussy
94805 Villejuif Cedex
FranceRekrutierend» Google-Maps
Istituto Nazionale Tumori Fondazione G. Pascale
80131 Napoli
ItalyRekrutierend» Google-Maps
National Cancer Center Hospital
104-0045 Chuo-Ku
JapanRekrutierend» Google-Maps
Kansai Medical University Hospital
573-1191 Hirakata
JapanRekrutierend» Google-Maps
National Cancer Center Hospital East
277-8577 Kashiwa
JapanRekrutierend» Google-Maps
Kobe City Medical Center General Hospital
650-0047 Kobe-City,
JapanRekrutierend» Google-Maps
Aichi Cancer Center Hospital
464-8681 Nagoya-Shi
JapanRekrutierend» Google-Maps
Okayama University Hospital
700-8558 Okayama
JapanRekrutierend» Google-Maps
Seoul National University Bundang Hospital
13620 Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Hospital
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Samsung Medical Center
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Oncologic Hospital, Puerto Rico Medical Center
OO935 Rio Piedras
Puerto RicoRekrutierend» Google-Maps
Inst. Cat. Doncologia-H Duran I Reynals
08908 Hospitalet de Llobregat, Barcelona
SpainZurückgezogen» Google-Maps
Hosp. Gral. Univ. Gregorio Marañon
28009 Madrid
SpainRekrutierend» Google-Maps
Kaohsiung Medical University Chung-Ho Memorial Hospital
807 Kaohsiung
TaiwanRekrutierend» Google-Maps
Chung Shan Medical University Hospital
402 Taichung
TaiwanRekrutierend» Google-Maps
National Cheng Kung University Hospital
704 Tainan
TaiwanRekrutierend» Google-Maps
National Taiwan University Hospital
10002 Taipei City
TaiwanRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to confirm the tolerability of recommended Phase 2 dose (RP2D)

of Lazertinib (Phase 1), to determine the tolerability and identify the recommended Phase 2

combination dose of Lazertinib when combined with Amivantamab (Phase 1b), to characterize the

safety and tolerability of Lazertinib and Amivantamab combinations at the RP2CD in

participants with advanced non-small cell lung cancer (NSCLC) with documented advanced or

metastatic epidermal growth factor receptor (EGFR) mutation (Phase 1b expansion cohorts A, B

and C), to estimate the antitumor activity of Lazertinib and Amivantamab combinations at the

RP2CD in participants with advanced NSCLC with documented advanced or metastatic EGFR

mutation (Phase 1b expansion cohorts A, B and C), to identify the recommended Phase 2 dose

(RP2ChD) of Lazertinib when combined with Amivantamab and standard of care chemotherapy and

to determine the tolerability of the Lazertinib, Amivantamab, and platinum-doublet

chemotherapy (LACP) combination (Phase 1b LACP combination cohort) and to characterize the

safety and tolerability of Lazertinib at the RP2ChD and Amivantamab and standard of care

chemotherapy in participants with advanced or metastatic EGFR-mutated NSCLC (Phase 1b LACP

combination cohort).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 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. Phase 1b expansion Cohort A, B and C: 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. 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. 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. 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

- 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

Exclusion Criteria:

- Participant has an uncontrolled illness, including but not limited uncontrolled

diabetes, ongoing or active infection (includes infection requiring treatment with

antimicrobial therapy [participants will be required to complete antibiotics 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 antiPD-1 or anti Programmed 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 (both Phase 1 and Phase 1b)

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

Studien-Rationale

Primary outcome:

1. Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1) (Time Frame - Until the end of first cycle (21 days for Phase 1)):
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

2. Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b) (Time Frame - Until the end of first cycle (28 days for Phase 1b)):
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

3. Overall Response Rate (ORR) (Phase 1b expansion) (Time Frame - Up to 2 years):
ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria.

4. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion) (Time Frame - Up to 2 years):
Adverse events (AEs) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Criteria Version 5.0 in participants treated at the RP2CD regimen of Lazertinib and Amivantamab combination therapy. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

5. Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP]) (Time Frame - Until the end of first cycle (21 days for Phase 1b combination LACP)):
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

6. Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP) (Time Frame - Up to 2 years):
AEs defined by the NCI-CTCAE criteria version 5.0 in participants treated with LACP combination regimen. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Secondary outcome:

1. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1 and Phase 1b) (Time Frame - Up to 1.8 years):
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

2. Plasma Concentration of Lazertinib (Phase 1 and Phase 1b) (Time Frame - Up to End of Treatment [EOT]) (30 days after last dose) (up to 1.8 years)):
Plasma samples will be analyzed to determine concentrations of Lazertinib.

3. Serum Concentration of Amivantamab (Phase 1b) (Time Frame - Up to EOT (30 days after last dose) (up to 1.8 years)):
Serum samples will be analyzed to determine concentrations of Amivantamab.

4. Number of Participants with Anti-drug Antibodies Against Amivantamab (Phase 1b) (Time Frame - Up to EOT (30 days after last dose) (up to 1.8 years)):
Number of participants with anti-drug antibodies against Amivantamab will be reported.

5. Progression free survival (PFS) (Phase 1b Expansion) (Time Frame - Up to 1.8 years (end of treatment)):
PFS is defined as the time from first infusion of study intervention to PD or death due to any cause.

6. Time to Treatment Failure (TTF) (Phase 1b Expansion) (Time Frame - Up to 2 years):
TTF is defined as the time from the first administration of the study intervention to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond as determined by the investigator using RECIST 1.1 criteria.

7. Overall Survival (OS) (Phase 1b Expansion) (Time Frame - Up to 2 years):
OS is defined as the time from first infusion of study intervention to death due to any cause as determined by the investigator using RECIST 1.1 criteria.

8. Duration of Response (DOR) (Phase 1b expansion) (Time Frame - Up to 2 years):
DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.

9. Clinical Benefit Rate (CBR) (Phase 1b expansion) (Time Frame - Up to 2 years):
CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.

Studien-Arme

  • 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 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 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 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 and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Geprüfte Regime

  • Lazertinib (JNJ-73841937):
    Lazertinib will be administered orally.
  • Amivantamab (JNJ-61186372):
    Amivantamab will be administered as an intravenous (IV) infusion.
  • Carboplatin:
    Carboplatin will be administered as IV infusion.
  • Pemetrexed:
    Pemetrexed will be administered as IV infusion.

Quelle: ClinicalTrials.gov


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