Trial Title:
Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer
NCT ID:
NCT02609776
Condition:
Non-Small-Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carboplatin
Pemetrexed
Amivantamab-vmjw
Lazertinib
Antibodies, Bispecific
Conditions: Keywords:
Non-Small-Cell Lung Cancer
Amivantamab
First-in-Human
Human Bispecific Epidermal Growth Factor Receptor (EGFR)
c-Mesenchymal-Epithelial Transition (cMet) Antibody
JNJ372
Exon 20
Exon 20 insertion
Tyrosine Kinase Inhibitor (TKI) Resistant
TKI Resistance
EGFR C797s
Met Amplification
Met + EGFR bispecific
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Amivantamab
Description:
The first cohort of participants will receive IV infusions of Amivantamab 140 mg as
monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased
dose level until maximum tolerated dose is reached or all planned doses are administered.
Participants will receive lazertinib and Amivantamab at predefined dose levels, based
upon observed safety and protocol defined criteria. The duration of each treatment cycle
is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab,
administered on a 21-day cycle, in combination with the administration of standard of
care carboplatin and pemetrexed.
Arm group label:
Part 1:Amivantamab Monotherapy+Combination Dose Escalations
Other name:
JNJ-61186372
Intervention type:
Drug
Intervention name:
Amivantamab
Description:
Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in
combination lazertinib at RP2CD regimen as determined in Part 1.
Arm group label:
Part 2:Amivantamab Monotherapy+Combination Dose Expansion
Other name:
JNJ-61186372
Intervention type:
Drug
Intervention name:
Lazertinib
Description:
Lazertinib will be administered in combination with Amivantamab at predefined dose
levels, based upon observed safety and protocol defined criteria. Lazertinib will be
administered daily on the 28-day Amivantamab treatment cycle.
Arm group label:
Part 1:Amivantamab Monotherapy+Combination Dose Escalations
Arm group label:
Part 2:Amivantamab Monotherapy+Combination Dose Expansion
Other name:
JNJ-73841937
Other name:
YH25448
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Participants will receive carboplatin in combination with pemetrexed and Amivantamab as
an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.
Arm group label:
Part 1:Amivantamab Monotherapy+Combination Dose Escalations
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Participants will receive pemetrexed in combination with carboplatin and Amivantamab as
an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.
Arm group label:
Part 1:Amivantamab Monotherapy+Combination Dose Escalations
Summary:
The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary
efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to
determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2
combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose
(RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care
carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced
non-small cell lung cancer (NSCLC).
Detailed description:
This open label (all participants know the identity of the study drug), multicenter (more
than one study site), first-in-human study consists of 2 parts. Part 1 is a Amivantamab
Monotherapy and Combination Dose Escalations and Part 2 Amivantamab Monotherapy and
Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be
enrolled into cohorts at increasing dose levels of Amivantamab monotherapy, the RP2CD of
the Amivantamab and lazertinib combination which will be administered in 28 day treatment
cycles, and RP2q3W of Amivantamab in combination with standard of care carboplatin and
pemetrexed (chemotherapy combination) which will be administered in 21 day treatment
cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum
administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional
3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting
toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new
cohort of 3 participants. Data from Part 1 will be used to determine one or more RP2D
regimen(s). In Part 2, participants with documented epidermal growth factor receptor
(EGFR) mutations and measurable disease, whose disease has progressed after previous
treatment will be enrolled and receive Amivantamab at the RP2D determined in Part 1 as a
monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD
regimen. For both parts, the study consists of following periods: an optional
pre-Screening period; a Screening period (up to 28 days prior to the first dose of study
drug); a Treatment period (first dose of study drug until 30(+7) days after the last dose
of study drug or prior to starting any subsequent anti-cancer treatment, whichever comes
first); and a Follow Up period (approximately 6 months). All participants will be
followed for survival in the post-treatment follow-up period until the end of study and
safety will be monitored throughout the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participant must have histologically or cytologically confirmed non-small cell lung
cancer (NSCLC) that is metastatic or unresectable. Participants must have either
progressed after prior standard of care therapy (Cohorts C and hepatocyte growth
factor receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine
kinase inhibitor [TKI]; Cohort D: platinum-based chemotherapy; MET-2: per regional
standard of care; Cohorts wild-type adenocarcinoma (WT-Ad) and wild-type squamous
cell carcinoma (WT-Sq): platinum-containing chemotherapy and programmed death- 1/
ligand-1 (PD-1/L1) therapy, either as a combined regimen or as separate lines of
therapy) for metastatic disease, or be ineligible for, or have refused all other
currently available therapeutic options. In cases where participants refuse
currently available therapeutic options, this must be documented in the study
records. For Part 1 Chemotherapy Combination Cohort only: Participants must have
histologically or cytologically confirmed NSCLC that is metastatic or unresectable
and be eligible for treatment with combination carboplatin and pemetrexed, in
accordance with standard of care, and be willing to receive additional
investigational therapy with Amivantamab
- For Part 1 Combination Dose Escalation with lazertinib only: Participants must have
been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be
treatment naïve for metastatic disease, without access to third generation TKI in
the front-line setting, or (b) have progressed after front-line treatment with first
(erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for
Cohort MET-1, or (c) have been treated with a third generation TKI (e.g.,
osimertinib) in either the front line or second-line setting, and are not eligible
for enrollment in either Cohort C or MET-1. For Part 1 Chemotherapy Combination
Cohort: Participants may be diagnosed with EGFR mutated or EGFR wild type NSCLC. For
Part 2 Cohorts C, D, MET-1, and MET-2 only: Participants must also have disease with
a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation
(includes both inhibitor sensitive primary mutations such as Exon 19 deletion and
L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as
Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping
mutation (Cohort MET-2). Documentation of primary activating EGFR or cMet mutation
eligibility by CLIA-certified laboratory (or equivalent) testing is required. For
Part 2 Cohorts WT-Ad and WT-Sq: Participants must have wild-type EGFR, anaplastic
lymphoma kinase (ALK), and absence of MET Exon 14 skipping mutation as tested by the
Food and Drug Administration (FDA) approved test or a CLIA-certified laboratory (or
equivalent). The pathology report or equivalent must be in the medical record for
verification. Where testing for EGFR and ALK are not part of standard of care for
participants with squamous cell carcinoma histology, documentation of the absence of
these mutations is not necessary for enrollment into the WT-Sq cohort
- For Part 1: Participant must have evaluable disease. For Part 2: Participant must
have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
- For Part 2: Cohorts A and B: Participants EGFR mutated disease must have most
recently progressed following treatment with a marketed EGFR inhibitor. Exception:
In participants diagnosed with mutations associated with de novo EGFR inhibitor
resistance (for example, Exon 20 insertions), only previous treatment with
combination platinum-based chemotherapy is required. Cohort C: Participants with
primary EGFR mutated disease, with a documented EGFR alteration (example, C797S)
mediating resistance to previous treatment with a third generation EGFR TKI (for
example, osimertinib), in participants with primary Exon 20ins disease, the
documented EGFR alteration may arise following treatment with a TKI with known
activity against Exon 20ins disease (for example, poziotinib). Cohort D:
participants must have been previously diagnosed with an EGFR Exon 20 insertion and
have not been previously treated with a TKI with known activity against Exon 20ins
disease (example, poziotinib). Cohort MET-1: Participants with documented primary
EGFR mutated disease and documented MET amplification or MET mutation after
progression on any EGFR TKI. Participants with disease characterized by both MET
amplification and EGFR resistance mutations to prior third generation EGFR TKI will
be preferentially enrolled into Cohort C. Participants may have received or have
been intolerant to prior platinum-based chemotherapy. Cohort MET-2: Participants
with documented primary MET Exon 14 skipping mutation non-small cell lung cancer
(NSCLC). Cohort E (combination Amivantamab and lazertinib): Participants must have
been diagnosed with EGFR Exon 19del or L858R activating mutation and have progressed
after first or second-line treatment with a third generation TKI (e.g.,
osimertinib). Cohort WT-Ad: Participant must have been diagnosed with NSCLC of
adenocarcinoma histology, with positive EGFR and/or MET expression as detected on a
validated immunohistochemistry (IHC) assay performed by the central laboratory and
have progressed on prior platinum containing chemotherapy and PD-1/L1 therapy,
either as a combined regimen or as a separate line of therapy. Eligibility may be
determined through IHC analysis of either archival (pre-screening) or mandatory
fresh tumor tissue collected during the Screening period. Cohort WT-Sq: Participant
must have been diagnosed with NSCLC of squamous cell carcinoma histology, with
positive EGFR and/or MET expression as detected on a validated IHC assay performed
by the central laboratory and have progressed on prior platinum-containing
chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line
of therapy. Eligibility may be determined through IHC analysis of either archival
(pre-screening) or mandatory fresh tumor tissue collected during the Screening
- Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0
or 1
Exclusion Criteria:
- Participant has uncontrolled inter-current illness, including but not limited to
poorly controlled hypertension, or diabetes, ongoing or active infection, (that is,
has discontinued all antibiotics for at least one week prior to first dose of study
drug), or psychiatric illness/social situation that would limit compliance with
study requirements. Participants with medical conditions requiring chronic
continuous oxygen therapy are excluded. For Part 1 Chemotherapy Combination Cohort
only: additionally, participants with active bleeding diathesis
- Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or
treatment with an investigational anticancer agent within 2 weeks or 4 half-lives
whichever is longer, before the first administration of study drug. For agents with
long half-lives, the maximum required time since last dose is 4 weeks. Toxicities
from previous anti-cancer therapies should have resolved to baseline levels or to
Grade 1 or less, (except for alopecia [any grade], Grade less than or equal to [<=]
2 peripheral neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone
replacement). For Part 1 Combination Dose Escalation: Any previous treatment with
systemic anti-cancer immunotherapy, including but not limited to anti-PD-1,
anti-PD-L1, and anti-CTLA-4 agents. For Part 1 Chemotherapy Combination Cohort only:
Any previous treatment with systemic anti-cancer immunotherapy in the past 3 months
or localized radiotherapy to lung within the past 6 months. For Part 2 only: Cohorts
A and B: Prior treatment with chemotherapy for metastatic disease is not allowed
unless the tumor mutation carries de-novo resistance to EGFR TKI (example, Exon 20
insertions). Cohort C and MET-1: Prior treatment with more than 2 lines of cytotoxic
chemotherapy for metastatic disease (maintenance therapy is not included). Cohort D:
Previous treatment with an EGFR TKI with activity against EGFR Exon 20 insertions
(such as poziotinib). Cohort E (combination Amivantamab and lazertinib): Any
previous treatment in the metastatic setting with other than a first, second, or
third generation EGFR TKI. Cohorts WT-Ad and WT-Sq: more than three lines of prior
systemic therapy in the metastatic setting
- Participants with untreated brain metastases. Participants with definitively,
locally-treated metastases that are clinically stable and asymptomatic for at least
2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 mg
prednisone or equivalent) for at least 2 weeks prior to study treatment are
eligible. Exception: participants with asymptomatic, untreated brain metastases,
each less than 1 cm in diameter, may be eligible for Amivantamab and lazertinib
combination therapy in the Part 1 Combination Dose Escalation or Part 2 Combination
Expansion Cohort E
- Participant has a history of malignancy other than the disease under study within 3
years before Screening (exceptions are squamous and basal cell carcinomas of the
skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the
investigator, with concurrence with the sponsor's medical monitor, is considered
cured with or minimal risk of recurrence within a year from Screening)
- Participant has not fully recovered from major surgery or significant traumatic
injury prior the first dose of study drug or expects to have major surgery during
the study period or within 6 months after the last dose of study drug
- Participant has, or will have, any of the following: a. An invasive operative
procedure with entry into a body cavity, within 4 weeks or without complete recovery
before Cycle 1 Day 1. Thoracentesis, if needed, and percutaneous biopsy for baseline
tumor tissue sample may be done less than 4 weeks prior to Cycle 1 Day 1, as long as
the participant has adequately recovered from the procedure prior to the first dose
of study drug in the clinical judgement of the investigator; b. Significant
traumatic injury within 3 weeks before the start of Cycle 1 Day 1 (all wounds must
be fully healed prior to Day 1); c. Any medical condition that requires intact wound
healing capacity and is expected to endanger subject safety if wound healing
capacity would be severely reduced during administration of the investigational
agent; d. Expected major surgery while the investigational agent is being
administered or within 6 months after the last dose of study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Address:
City:
Duarte
Country:
United States
Facility:
Address:
City:
La Jolla
Country:
United States
Facility:
Address:
City:
Orange
Country:
United States
Facility:
Address:
City:
Santa Monica
Country:
United States
Facility:
Address:
City:
West Hollywood
Country:
United States
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Address:
City:
Tampa
Country:
United States
Facility:
Address:
City:
Chicago
Country:
United States
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Address:
City:
Bethesda
Country:
United States
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Address:
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Boston
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United States
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Detroit
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United States
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Rochester
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United States
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Saint Louis
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United States
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New York
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United States
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Portland
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United States
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Philadelphia
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United States
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Houston
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United States
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Fairfax
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United States
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Camperdown
Country:
Australia
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Address:
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Heidelberg
Country:
Australia
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Address:
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Kogarah
Country:
Australia
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Address:
City:
Murdoch
Country:
Australia
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Address:
City:
Woolloongabba
Country:
Australia
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Address:
City:
Toronto
Country:
Canada
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Beijing
Country:
China
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Address:
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Changchun
Country:
China
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Address:
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Changsha
Country:
China
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Chengdu
Country:
China
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Chongqing
Country:
China
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Guangzhou
Country:
China
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Hangzhou
Country:
China
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Address:
City:
Hefei
Country:
China
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Address:
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Nanchang
Country:
China
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Address:
City:
Nanjing
Country:
China
Facility:
Address:
City:
Wuhan
Country:
China
Facility:
Address:
City:
Zhengzhou
Country:
China
Facility:
Address:
City:
Bordeaux
Country:
France
Facility:
Address:
City:
Dijon
Country:
France
Facility:
Address:
City:
Lyon Cedex 8
Country:
France
Facility:
Address:
City:
Marseille
Country:
France
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Address:
City:
Paris
Country:
France
Facility:
Address:
City:
Saint-Herblain Cedex
Country:
France
Facility:
Address:
City:
Villejuif Cedex
Country:
France
Facility:
Address:
City:
Chuo Ku
Country:
Japan
Facility:
Address:
City:
Hyogo
Country:
Japan
Facility:
Address:
City:
Kashiwa
Country:
Japan
Facility:
Address:
City:
Kurume
Country:
Japan
Facility:
Address:
City:
Nagoya Shi
Country:
Japan
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Address:
City:
Niigata
Country:
Japan
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Address:
City:
Osaka
Country:
Japan
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Tokyo
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Japan
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Wakayama
Country:
Japan
Facility:
Address:
City:
Yonago
Country:
Japan
Facility:
Address:
City:
Cheongju-si
Country:
Korea, Republic of
Facility:
Address:
City:
Goyang-si
Country:
Korea, Republic of
Facility:
Address:
City:
Incheon
Country:
Korea, Republic of
Facility:
Address:
City:
Seongnam-si
Country:
Korea, Republic of
Facility:
Address:
City:
Seoul
Country:
Korea, Republic of
Facility:
Address:
City:
A Coruna
Country:
Spain
Facility:
Address:
City:
Barcelona
Country:
Spain
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Madrid
Country:
Spain
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City:
Malaga
Country:
Spain
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Santander
Country:
Spain
Facility:
Address:
City:
Seville
Country:
Spain
Facility:
Address:
City:
Kaohsiung
Country:
Taiwan
Facility:
Address:
City:
Taichung
Country:
Taiwan
Facility:
Address:
City:
Taipei City
Country:
Taiwan
Facility:
Address:
City:
Taipei
Country:
Taiwan
Facility:
Address:
City:
Manchester
Country:
United Kingdom
Facility:
Address:
City:
Newcastle upon Tyne
Country:
United Kingdom
Facility:
Address:
City:
Sutton
Country:
United Kingdom
Start date:
May 24, 2016
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Janssen Research & Development, LLC
Agency class:
Industry
Source:
Janssen Research & Development, LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02609776
