This study has been transitioned to CTIS with ID 2023-506576-27-00 check the CTIS register for the current data. The hypothesis is that the amivantamab and lazertinib combination (Arm A) will demonstrate superior PFS compared with single-agent…
ID
Source
Brief title
Condition
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of the amivantamab and lazertinib combination, compared
with osimertinib, in participants with EGFR mutation (Exon 19del or Exon 21
L858R substitution) positive, locally advanced or metastatic NSCLC
Endpoint
• PFS (using RECIST v1.1 guidelines), as assessed by blinded independent
central review
Secondary outcome
a) To further assess the clinical benefit achieved using the amivantamab and
lazertinib combination compared with osimertinib in participants with EGFR
mutation positive, locally advanced or metastatic NSCLC
endpoints
• Overall survival
• Objective response rate
• Duration of response
• PFS after first subsequent therapy (PFS2)
• Time to symptomatic progression
• Intracranial PFS
b)To evaluate the safety and tolerability of the amivantamab and lazertinib
combination compared with osimertinib
endpoint
• Incidence and severity of adverse events and laboratory abnormalities
Background summary
Worldwide, lung cancer is the most commonly diagnosed cancer. In NSCLC the most
prevalent actionable driver mutations result in the activation of epidermal
growth factor receptor (EGFR). Osimertinib and Lazertinib are EGFR tyrosine
kinase inhibitors (TKIs). Amivantamab is a novel bispecific antibody that
targets the extracellular domain of both EGFR and MET and can inhibit tumor
growth driven by EGFR and mesenchymal-epithelial transition (MET) receptors.
Lazertinib inhibits primary activating Exon 19dell and Exon 21 L858R
substitution EGFR mutations, and the EGFR T790M+ resistance mutation. The
hypothesis is that the amivantamab and lazertinib combination (Arm A) will
demonstrate superior PFS compared with single-agent osimertinib (Arm B). The
study consists of 3 phases: Screening Phase, Treatment Phase and Follow-up
Phase. Participants will undergo response evaluation criteria in solid tumors
(RECIST 1.1), pharmacokinetics, and safety evaluations (adverse events,
laboratory tests, vital sign measurements, physical examinations).
Study objective
This study has been transitioned to CTIS with ID 2023-506576-27-00 check the CTIS register for the current data.
The hypothesis is that the amivantamab and lazertinib combination (Arm A) will
demonstrate superior PFS compared with single-agent osimertinib (Arm B).
Study design
The study will include a Screening Phase, a Treatment Phase, and a Follow-up
Phase. Participants must complete screening procedures within 28 days before
randomization. To be randomized, all participants must have been previously
diagnosed with NSCLC, characterized by Exon 19del or Exon 21 L858R substitution
EGFR mutations.
The Treatment Phase for a participant will begin on Cycle 1 Day 1 and continue
as 28 day cycles until the End of Treatment visit, approximately 30 days after
discontinuation of study treatment. Participants who discontinue study
treatment for any reason will be followed for survival and symptomatic
progression in the Follow up Phase. The Follow-up Phase starts after the End of
Treatment Visit and continues until the end of study, death, lost to follow up,
or withdrawal of consent, whichever comes first.
Intervention
• Arm A: participants will be assigned to open label treatment with the
combination of amivantamab (1050 mg for body weight <80 kg and 1400 mg for body
weight >=80 kg by intravenous [IV] infusion, once weekly for the first 4 weeks
and then once every 2 weeks) and lazertinib (240 mg orally, once daily).
• Arm B: participants will receive double blind treatment with single agent
osimertinib (80 mg orally, once daily).
• Arm C: participants will receive double blind treatment with single agent
lazertinib (240 mg orally, once daily).
Study burden and risks
Risks / side effects from tests:
Blood draw: Taking blood may cause bruising 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: There are no known risks or side effects with having an MRI. If a
contrast material is used, your investigator will tell you about possible side
effects or allergic reaction.
MUGA Scan: 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
doctor will tell you about possible side effects or allergic reaction.
Intravenous (IV) line: Use of an intravenous line for study treatment
administration, imaging and other tests may cause discomfort, irritation, minor
bruising, bleeding, or injection leakage, and rarely causes nausea and light
dizziness.
Radiation burden
With a CT-scan we use X-ray radiation. The radiation burden in this study is
about 20 mSv per CT scan. In comparison: the background radiation in the
Netherlands is about 2.5 mSv, per year.
If you often participate in scientific research with a radiation burden, you
should discuss with the investigator whether participation at this time is
sensible.
The radiation used during the study may cause damage to your health. This risk,
however, is small. We nevertheless advise you not to participate in another
scientific study with a radiation burden in the near future. There is no
objection to research or treatment with radiation for medical reasons.
7. Possible advantages and disadvantages
It is important that you properly consider the possible advantages and
disadvantages before you decide to participate.
Taking part in this study may improve your condition. This benefit is not
guaranteed to happen and there may not be any benefit to you by being in this
study. During the study, your condition may stay the same or get worse. Your
participation may help future patients.
Disadvantages of participation in the study may be
- possible side effects;
- possible adverse effects/discomforts of the measurements in the study.
Participation in the study also means:
- that you lose additional time;
- an additional or an extended hospitalisation;
- (additional) testing;
- that you have appointments that you have to attend;
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
1. Participant must be >=18 years of age
2. Criterion modified per Amendment 1
2.1 Participant must have newly diagnosed, histologically or cytologically
confirmed, locally advanced or metastatic NSCLC that is treatment naïve and not
amenable to curative therapy including surgical resection or chemoradiation.
3. Criterion modified per Amendment 1.
3.1 The tumor (meeting criteria described in Inclusion Criterion no. 2) harbors
Exon 19del or Exon 21 L858R substitution, as detected by an FDA-approved or
other validated test in a CLIA certified laboratory (sites in the US) or an
accredited local laboratory (sites outside of the US) in accordance with site
standard of care. (Note: A copy of the test report documenting the EGFR
mutation must be included in the participant records and must
lso be submitted to the sponsor.)
4. Criterion modified per Amendment 1.
4.1 Mandatory submission of unstained tissue from tumor meeting criteria
described in Inclusion Criterion no. 2 (in a quantity sufficient to allow for
central analysis of EGFR mutation status) and blood (for ctDNA, digital droplet
polymerase chain reaction [ddPCR], and pharmacogenomic analysis). See Section
8.7.
5. Any toxicities from prior anticancer therapy must have resolved to Common
Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline level.
6. at least 1 measurable lesion, according to RECIST v1.1 that has not been
previously irradiated.
Full details of inclusion criteria can be found in section 5.1 of the study
protocol.
Exclusion criteria
1. Criterion modified per Amendment 2.
1.1 Participant has received any prior systemic treatment at any time for
locally advanced stage III or metastatic stage IV disease (adjuvant or
neoadjuvant therapy for stage I or II disease is allowed, if administered more
than 12 months prior to the development of locally advanced or metastatic
disease).
2. Criterion modified per Amendment 1.
2.1 Participant has symptomatic brain metastases. A participant with
asymptomatic or previously treated and stable brain metastases may participate
in this study.
3. Participant has an active or past medical history of leptomeningeal disease.
4. Criterion modified per Amendment 1.
4.1 Participant with untreated spinal cord compression. A participant that has
been definitively treated with surgery or radiation and has a stable
neurological status for at least 2 weeks prior to randomization is eligible
provided they are off corticosteroid treatment or receiving low-dose
corticosteroid treatment <=10 mg/day prednisone or equivalent.
6. Participant has an active or past medical history of
ILD/pneumonitis, including drug-induced or radiation ILD/pneumonitis.
10. Participant has known allergy, hypersensitivity, or intolerance to the
excipients used in formulation of amivantamab, lazertinib, or osimertinib, or
any contraindication to the use of osimertinib
Full details of exclusion criteria can be found in section 5.2 of the study
protocol.
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 | CTIS2023-506576-27-00 |
| EudraCT | EUCTR2020-000743-31-NL |
| ClinicalTrials.gov | NCT04487080 |
| CCMO | NL74637.056.20 |