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
Study Director
Janssen Research & Development, LLC
Kontakt
Kontakt:
Phone: 844-434-4210
E-Mail: JNJ.CT@sylogent.com» Kontaktdaten anzeigen
Studienlocations
(3 von 80)
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
45147 Essen
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
60590 Frankfurt am Main
(Hessen)
GermanyNoch nicht rekrutierend» Google-Maps
82131 Gauting
(Bayern)
GermanyRekrutierend» Google-Maps
06120 Halle (Saale)
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
69126 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
58675 Hemer
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Kerpener Straße 62
50937 Köln
DeutschlandNoch nicht rekrutierend» Google-Maps
51109 Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
26121 Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps
70376 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
90089-9173 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
92868 Orange
United StatesNoch nicht rekrutierend» Google-Maps
94158 San Francisco
United StatesNoch nicht rekrutierend» Google-Maps
94305 Stanford
United StatesRekrutierend» Google-Maps
90048 West Hollywood
United StatesNoch nicht rekrutierend» Google-Maps
32224 Jacksonville
United StatesZurückgezogen» Google-Maps
33612 Tampa
United StatesNoch nicht rekrutierend» Google-Maps
02114 Boston
United StatesNoch nicht rekrutierend» Google-Maps
02118 Boston
United StatesRekrutierend» Google-Maps
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps
48201 Detroit
United StatesRekrutierend» Google-Maps
55905 Rochester
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63110 Saint Louis
United StatesRekrutierend» Google-Maps
10016 New York
United StatesRekrutierend» Google-Maps
10032 New York
United StatesRekrutierend» Google-Maps
97213 Portland
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19104 Philadelphia
United StatesRekrutierend» Google-Maps
84112 Salt Lake City
United StatesNoch nicht rekrutierend» Google-Maps
22031 Fairfax
United StatesRekrutierend» Google-Maps
98109 Seattle
United StatesNoch nicht rekrutierend» Google-Maps
100142 Beijing
ChinaNoch nicht rekrutierend» Google-Maps
130021 Changchun
ChinaRekrutierend» Google-Maps
410013 Changsha
ChinaNoch nicht rekrutierend» Google-Maps
610041 Chengdu
ChinaRekrutierend» Google-Maps
400030 Chongqing
ChinaRekrutierend» Google-Maps
440112 Guangzhou
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310022 Hang Zhou
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250013 Jinan
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330006 Nanchang
ChinaNoch nicht rekrutierend» Google-Maps
200030 Shanghai
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110022 Shenyang
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300000 Tianjin
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430022 Wuhan
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710061 Xi'an
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33000 Bordeaux
FranceRekrutierend» Google-Maps
69373 Lyon Cedex 8
FranceRekrutierend» Google-Maps
13005 Marseille
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75005 Paris
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86000 Poitiers
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94163 Saint Mande
FranceRekrutierend» Google-Maps
94805 Villejuif Cedex
FranceRekrutierend» Google-Maps
Milano
ItalyRekrutierend» Google-Maps
80131 Napoli
ItalyRekrutierend» Google-Maps
48121 Ravenna
ItalyRekrutierend» Google-Maps
104-0045 Chuo-Ku
JapanRekrutierend» Google-Maps
573-1191 Hirakata
JapanRekrutierend» Google-Maps
277-8577 Kashiwa
JapanRekrutierend» Google-Maps
650-0047 Kobe-City,
JapanRekrutierend» Google-Maps
464-8681 Nagoya-Shi
JapanRekrutierend» Google-Maps
700-8558 Okayama
JapanRekrutierend» Google-Maps
411-8777 Sunto-gun
JapanRekrutierend» Google-Maps
13620 Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
03722 Seoul
Korea, Republic ofRekrutierend» Google-Maps
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
OO935 Rio Piedras
Puerto RicoRekrutierend» Google-Maps
08028 Barcelona
SpainRekrutierend» Google-Maps
8035 Barcelona
SpainRekrutierend» Google-Maps
08908 Hospitalet de Llobregat, Barcelona
SpainZurückgezogen» Google-Maps
28009 Madrid
SpainRekrutierend» Google-Maps
28034 Madrid
SpainRekrutierend» Google-Maps
28040 Madrid
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28041 Madrid
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28050 Madrid
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41013 Seville
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807 Kaohsiung
TaiwanRekrutierend» Google-Maps
402 Taichung
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704 Tainan
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10002 Taipei City
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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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