A multicentre single-arm phase II trial of amivantamab, lazertinib plus bevacizumab in patients with EGFR-mutant advanced NSCLC with progression on previous third generation EGFR TKI
- Conditions
- lungcancerNon small cell lung cancer10038667
- Registration Number
- NL-OMON56289
- Lead Sponsor
- ETOP IBCSG Partners Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
1. Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to
radical therapy) or stage IV according to 8th TNM classification.
2. Presence of the sensitising EGFR-mutation (only patients with exon 19
deletion and/or L858R are eligible) and documentation of T790M status, tested
locally by an accredited laboratory.
3.Radiologically confirmed disease progression on previous treatment with
osimertinib or lazertinib. Treatment with osimertinib or lazertinib must have
been stopped at least 8 days before enrolment.
4.Achieved objective clinical benefit from osimertinib or lazertinib treatment
(e.g., documented PR/ CR or SD for >=6 months while on osimertinib or lazertinib
treatment).
5.Measurable disease as defined according to RECIST v1.1.
6. ECOG performance status 0-2
7. Adequate haematological, renal and liver function.
1. Patients with known small cell lung carcinoma (SCLC).
2. Patients with symptomatic brain metastases. Patients with asymptomatic or
previously treated and stable brain metastases may participate in this study.
Patients who have received definitive radiotherapy or surgery for symptomatic
or unstable brain metastases and have been clinically stable and asymptomatic
for at >= 2 weeks before enrolment are eligible, provided they have been either
off corticosteroid treatment or are receiving low-dose corticosteroid treatment
(<=10 mg/day prednisone or equivalent) for at least 2 weeks prior to enrolment.
3. Patients with an active or past medical history of leptomeningeal disease.
4. Patients with untreated spinal cord compression. Patients who have been
definitively treated with surgery or radiotherapy and have a stable
neurological status for >=2 weeks prior to enrollment
are eligible provided they are off corticosteroid treatment or are receiving
low-dose corticosteroid treatment <=10 mg/day prednisone or equivalent.
5. Patients with unresolved adverse events (other than alopecia) from prior
anticancer therapy that have not resolved to grade <=1 or baseline.
6. Patients with positive hepatitis B or hepatitis C antibody or other
clinically active infectious liver disease .
7. Patients who are positive for HIV.
8. Patients with active cardiovascular disease.
9. Patients with interstitial lung disease (ILD), including drug-induced ILD or
radiation pneumonitis.
10. Patients with a history of haemoptysis (>=2.5 mL of bright red blood per
episode) within 1 month prior to enrolment.
11. Patients with evidence of bleeding diathesis or coagulopathy (in the
absence of therapeutic anticoagulation).
12. History of hypersensitivity to either the drug substance or any excipients
in amivantamab, lazertinib and/ or bevacizumab.
13. Prior chemotherapy, prior treatment with bevacizumab or another
anti-angiogenic inhibitor or prior treatment with a MET/EGFR-targeting antibody.
14. Patients with a significant genetic predisposition to venous thromboembolic
events
(VTE, such as factor V Leiden) or patients with a history of VTE who are not
receiving
appropriate therapeutic anticoagulation according to NCCN or local guidelines.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective response rate (ORR) at 12 weeks according to RECIST v1.1</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Duration of Response (DoR)<br /><br>-Progression-free survival (PFS) according to RECIST v1.1<br /><br>- Disease control rate (DCR) according to RECIST v1.1<br /><br>- Overall survival (OS)<br /><br>- Safety and tolerability (CTCAE v5.0)</p><br>