This study has been transitioned to CTIS with ID 2023-506518-33-00 check the CTIS register for the current data. The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing…
ID
Source
Brief title
Condition
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed
by Blinded Independent Central Review (BICR) - Up to 17 months - PFS is defined
as the time from randomization until the date of objective disease progression
or death, whichever comes first, using Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.1.
Secondary outcome
Objective Response as Assessed by BICR
Up to 17 months
Objective response is defined as the percentage of participants who achieve
either a complete response (CR) or partial response (PR) as their best response
as defined by BICR using RECIST v1.1 criteria.
Overall Survival (OS)
Up to 48 months
Overall Survival is defined as the time from the date of randomization to the
date of participant's death due to any cause.
Duration of Response (DoR)
Up to 17 months
DoR is defined as the time from the date of first documented response (CR or
PR) until the date of documented progression or death, whichever comes first,
only for participants who achieve CR or PR.
Time to Subsequent Therapy (TTST)
Up to 17 months
TTST is defined as the time from the date of randomization to the start date of
the subsequent anti-cancer therapy following study treatment discontinuation,
or death whichever comes first.
Progression-Free Survival After First Subsequent Therapy (PFS2)
Up to 17 months
PFS2 is defined as the time from randomization until the date of second
objective disease progression, after initiation of subsequent anticancer
therapy, based on investigator assessment (after that used for PFS) or death,
whichever comes first.
Time to Symptomatic Progression (TTSP)
Up to 17 months
TTSP is defined as the time from randomization to documentation in the
electronic case report form (eCRF) of any of the following (whichever occurs
earlier): onset of new symptoms or symptom worsening that is considered by the
investigator to be related to lung cancer and requires either a change in
anticancer treatment and/or clinical intervention to manage symptoms.
Intracranial PFS
Up to 17 months
Intracranial PFS is defined as the time from randomization until the date of
objective intracranial disease progression or death, whichever comes first,
based on BICR using RECIST v1.1.
Number of Participants with Adverse Events (AEs)
Up to 48 months
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.
Number of Participants with Clinical Laboratory Abnormalities
Up to 48 months
Number of participants with clinical laboratory abnormalities (serum chemistry,
hematology, blood coagulation, and urinalysis) will be reported.
Serum Concentration of Amivantamab
Up to 17 months
Serum samples will be analyzed to determine concentrations of amivantamab.
Plasma Concentration of Lazertinib
Up to 17 months
Plasma samples will be analyzed to determine concentrations of lazertinib.
Number of Participants with Anti-Amivantamab Antibodies
Up to 17 months
Number of participants with anti-amivantamab antibodies will be reported.
Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)
Up to 17 months
NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms
of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day
recall period. It contains five domains and accompanying items that will be
identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1
item), fatigue (2 items), and appetite (1 item). Each item uses a response
scale between 0 to 4, with higher scores indicating more severe symptomatology.
All five of these domains must be non-missing to compute a total score, with a
response range from 0 to 20 with higher scores indicating more severe
symptomatology.
European Organization of Research and Treatment of Cancer Quality of Life
Questionnaire Core 30 (EORTC-QLQ-C30) Score
Up to 17 months
The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health
status scale, 3 symptom scales, and 6 single symptom items. The responses are
reported using a verbal rating scale. The item and scale scores are transformed
to a 0 to 100 scale. A higher score represents greater HRQoL, better
functioning, and more (worse) symptoms.
Patient Reported Outcomes Measurement Information System-Physical Function
(PROMIS-PF)
Up to 17 months
PROMIS-PF is used to characterize and better understand overall health, level
of physical disability, and general well-being. Physical function is a
foundation for commonly used general and cancer-specific patient reported
outcomes (PRO) measures.
Background summary
Lung cancer is one of the most common types of cancer and is the most common
cause of death from cancer. NSCLC accounts for approximately 85 percent (%) of
lung cancers. Advanced NSCLC is a serious terminal illness that accounts for
approximately 20% of all cancer mortality, and until recently had a median
overall survival (OS) of approximately 1 year. Amivantamab (JNJ-61186372) is a
low fucose, fully human immunoglobulin (IgG)1-based bispecific antibody
directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine
kinase receptors. It shows clinical activity against tumors with primary
activating EGFR mutations Exon 19del and Exon 21 L858R substitution. Lazertinib
(JNJ-73841937; YH-25448) is an oral, highly potent, third-generation EGFR
tyrosine kinase inhibitor (TKI). It selectively inhibits both primary
activating EGFR mutations (Exon 19del, Exon 21 L858R substitution) and the EGFR
T790M resistance mutation, with less inhibition of wild-type EGFR. The study
consists of a Screening Phase (up to 28 days), a Treatment Phase (from
randomization until the End of Treatment visit) and a Follow-up Phase (from End
of Treatment Visit until the end of study, death, lost to follow-up, or
withdrawal of consent, whichever comes first). Safety will be assessed by
physical examinations, laboratory tests, vital signs, electrocardiograms,
Eastern Cooperative Oncology Group (ECOG) performance status, and monitoring of
adverse events (AEs). The total duration of the study is up to 48 months.
Study objective
This study has been transitioned to CTIS with ID 2023-506518-33-00 check the CTIS register for the current data.
The purpose of this study is to assess the efficacy of adding lazertinib to
amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and
amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and
pemetrexed (CP) in participants with locally advanced or metastatic epidermal
growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution
non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of
the extension cohort is to further describe the safety and efficacy for the
ACP-L dosing schedule versus ACP with additional data.
Study design
The study consists of a Screening Phase (up to 28 days), a Treatment Phase
(from randomization until the End of Treatment visit) and a Follow-up Phase
(from End of Treatment Visit until the end of study, death, lost to follow-up,
or withdrawal of consent, whichever comes first). Safety will be assessed by
physical examinations, laboratory tests, vital signs, electrocardiograms,
Eastern Cooperative Oncology Group (ECOG) performance status, and monitoring of
adverse events (AEs). The total duration of the study is up to 48 months.
Intervention
Arm A: LACP/ACP-L: LACP dosing (form study start until 6 November 2022):
participants will receive lazertinib orally along amivantamab, pemetrexed and
carboplatin starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21
days). After 4 cycles, participants will received amivantamab, pemetrexed and
Lazertinib as maintenance until disease progression. ACP-L dosing (from 7
November 2022 until study completion): Participants will receive amivantamab,
pemetrexed and carboplatin, starting on Cycle 1 Day 1 for 4 cycles (each cycle
consists of 21 days). Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner
if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days).
Beginning with Cycle 5 Day 1, participants will receive amivantamab, pemetrexed
and lazertinib as maintenance until disease progression.
Arm B CP (Carboplatin and Pemetrexed): Participants will receive Pemetrexed in
combination with Carboplatin as IV infusion for up to 4 cycles (each cycle
consists of 21 days). After 4 cycles, participants will receive Pemetrexed as
maintenance until disease progression.
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed): Participants will receive
Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles
(each cycle consists of 21 days). After 4 cycles, participants will receive
Amivantamab and Pemetrexed as maintenance until disease progression.
Arm A2 (Extension Cohort): ACP-L: Participants will receive Amivantamab and
Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days),
Lazertinib will start on C5D1 or sooner if carboplatin is discontinued
earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab,
Lazertinib as maintenance until disease progression.
Arm C2 (Extension Cohort): ACP: Participants will receive Amivantamab,
Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle
consists of 21 days). After 4 cycles, participants will receive Amivantamab and
Pemetrexed as maintenance until disease progression.
Study burden and risks
Risks/discomforts tests:
Blood draw Risk: Taking blood may cause bruising irritation at the place where
the needle goes into the skin. Fainting, and in rare cases infection, may occur.
ECG Risk: There is generally no risk with having an ECG. The sticky patches may
pull your skin or cause redness or itching.
CT Risk: CT scans do create low levels of radiation, which has a small
potential to cause cancer and other defects. However, the risk associated with
any one scan is small. If a contrast material is used, your investigator will
tell you about possible side effects or allergic reaction.
MRI Risk (including Brain MRI): Because radiation is not used, there is no risk
of exposure to radiation during MRI procedure. However please notify the
investigator if you have a metal object inside your body e.g. pacemaker.
Additionally, if a contrast material is used during MRI, your investigator will
tell you about possible side effects or allergic reaction.
MUGA Scan Risk: The tracer used for a MUGA scan produces a very small amount
of radiation. There is no significant risk from this amount of radiation. Your
investigator will tell you about possible side effects or allergic reaction.
Intravenous (IV) line Risk: Use of an intravenous line for trial treatment
administration, imaging and other tests may cause discomfort, irritation, minor
bruising, bleeding, or injection leakage, and rarely causes nausea, light
dizziness and air embolism.
Biopsy Risk (for optional sample): Your doctor will inform you in detail about
the procedures and risks associated with the biopsy since these will depend
upon where your tumor(s) are located in your body. Typical procedures involve
inserting a thin needle through the chest wall using images to guide exact
placement (*transthoracic needle biopsy*), or passing a scope through the mouth
into the windpipe, to get close enough to the tumor to reach it with a biopsy
tool (*bronchoscopy*). You will be given sedation and local anesthesia as
needed to make the procedure as comfortable as possible. In general, having a
biopsy can cause pain, swelling, bleeding, and/or infection at the site where
the biopsy needle or other instrument penetrates through your skin. Additional
risks of biopsy of tissue in the lung or chest cavity, depending on the
procedure used, include coughing, blood in sputum, throat irritation, wheezing
or increased difficulty breathing, need for additional oxygen to breathe,
leakage of air into the chest cavity which can result in collapse of the lung,
pneumonia, and very rarely, air entering the bloodstream. There is also the
rare possibility that having this procedure may shift some cells from the tumor
into the surrounding tissues (tissues that come into contact with the biopsy
needle). This means that the tumor may spread to that particular area. You will
be monitored for these complications and treated if any occur.
Fine Needle Aspirate: Complications after fine needle aspiration are rare.
Minor bleeding under the skin at the biopsy site can occur. This can result in
a tender, swollen area called a hematoma.
Possible advantages and disadvantages
It is important that you carefully weigh the possible advantages and
disadvantages before you decide to participate.
Participating in this study may improve your condition. Whether you will
benefit from participating in the study is not guaranteed, and it may also be
that you will not get any
benefit at all. During the study, your condition may stay the same or worsen.
Your participation may help future patients.
Disadvantages of participating in the study may include
- possible side effects;
- possible adverse effects/discomforts of the measurements in the study.
Participating in the study also means:
- that you will lose additional time;
- additional or prolonged hospitalization;
- (additional) tests;
- that you have appointments to keep.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria:- Participant must have at least 1 measurable lesion,
according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
that has not been previously irradiated- Participant must have histologically
or cytologically confirmed, locally advanced or metastatic, non-squamous
non-small cell lung cancer (NSCLC), characterized at or after the time of
locally advanced or metastatic disease diagnosis by either epidermal growth
factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation- A participant with
a history of brain metastases must have had all lesions treated as clinically
indicated (that is, no current indication for further definitive local
therapy). Any definitive local therapy to brain metastases must have been
completed at least 14 days prior to randomization and the participant can be
receiving no greater than10 milligrams (mg) prednisone or equivalent daily for
the treatment of intracranial disease- Participant must have Eastern
Cooperative Oncology Group (ECOG) status of 0 or 1- Any toxicities from prior
systemic anticancer therapy must have resolved to National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1
or baseline level (except for alopecia [any grade], Grade <= 2 peripheral
neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)- A
woman of childbearing potential must have a negative serum pregnancy test at
screening and within 72 hours of the first dose of study treatment and must
agree to further serum or urine pregnancy tests during the study- Participant
must have progressed on or after osimertinib monotherapy as the most recent
line of treatment. Osimertinib must have been administered as either the
first-line treatment for locally advanced or metastatic disease or in the
second- line setting after prior treatment with first- or second-generation
EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who
received either neoadjuvant and/or adjuvant treatment of any type are eligible
if progression to locally advanced or metastatic disease occurred at least 12
months after the last dose of such therapy and then the participant progressed
on or after osimertinib in the locally advanced or metastatic setting.
Treatment with osimertinib must be discontinued at least 8 days (4 half-lives)
prior to randomization (that is last dose no later than Day -8)
Exclusion criteria
Exclusion Criteria:- Participant received radiotherapy for palliative treatment
of NSCLC less than 14 days prior to randomization- Participant with symptomatic
or progressive brain metastases- Participant has history of or current evidence
of leptomeningeal disease, or participant has spinal cord compression not
definitively treated with surgery or radiation- Participant has known small
cell transformation- Participant has a medical history of interstitial lung
disease (ILD), including drug-induced ILD or radiation pneumonitis- Participant
has a history of clinically significant cardiovascular disease including, but
not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4
weeks prior to randomization; myocardial infarction; unstable angina; stroke;
transient ischemic attack; coronary/peripheral artery bypass graft; or acute
coronary syndrome. Participant has a significant genetic predisposition to
venous thromboembolic events. Participant has a prior history of venous
thromboembolic events and is not on appropriate therapeutic anticoagulation as
per National Comprehensive Cancer Network or local guidelines
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506518-33-00 |
| EudraCT | EUCTR2021-001825-33-NL |
| ClinicalTrials.gov | NCT04988295 |
| CCMO | NL78839.056.21 |