A Phase 3, Randomized Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib Versus Lazertinib as First-Line Treatment in Patients with EGFR Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- Conditions
- EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer harboring EGFR Exon 19del or L858R mutations10029107
- Registration Number
- NL-OMON54268
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the efficacy of the amivantamab and lazertinib combination, compared<br /><br>with osimertinib, in participants with EGFR mutation (Exon 19del or Exon 21<br /><br>L858R substitution) positive, locally advanced or metastatic NSCLC<br /><br>Endpoint<br /><br>• PFS (using RECIST v1.1 guidelines), as assessed by blinded independent<br /><br>central review</p><br>
- Secondary Outcome Measures
Name Time Method <p>a) To further assess the clinical benefit achieved using the amivantamab and<br /><br>lazertinib combination compared with osimertinib in participants with EGFR<br /><br>mutation positive, locally advanced or metastatic NSCLC<br /><br>endpoints<br /><br>• Overall survival<br /><br>• Objective response rate<br /><br>• Duration of response<br /><br>• PFS after first subsequent therapy (PFS2)<br /><br>• Time to symptomatic progression<br /><br>• Intracranial PFS<br /><br>b)To evaluate the safety and tolerability of the amivantamab and lazertinib<br /><br>combination compared with osimertinib<br /><br>endpoint<br /><br>• Incidence and severity of adverse events and laboratory abnormalities </p><br>