LAZERTINIB for Non-small cell lung cancer (EGFR-mutant, advanced)

Inclusion criteria

• {"criterion_text":"- Histologically confirmed, non-squamous NSCLC, stage IIIB/C (not suitable for radical therapy) or stage IV according to TNM classification (8th edition).\n- Presence of a sensitizing EGFR mutation (only patients with exon 19 deletion and/or L858R mutation are eligible) and documented T790M status, tested on site by an accredited laboratory.\n- Radiologically confirmed disease progression during prior treatment with osimertinib or lazertinib. Treatment with osimertinib must have been stopped at least 8 days prior to study enrollment.\n- Achievement of objective clinical benefit from treatment with osimertinib or lazertinib (e.g. documented partial response (PR) or complete response (CR) or stable disease (SD) for ≥6 months under treatment with osimertinib or lazertinib).\n- Measurable disease as defined by RECIST v1.1.\n- Age ≥18 years\n- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.\n- Life expectancy of ≥ 12 weeks\n- Adequate hematologic, renal and liver function.\n- Written patient information and informed consent."}

Exclusion criteria

• {"criterion_text":"- Patients with known small cell lung carcinoma (SCLC) transformation,\n- 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.\n- Patients with an active or past medical history of leptomeningeal disease.\n- 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 enrolment are eligible provided they are off corticosteroid treatment or are receiving low-dose corticosteroid treatment ≤10 mg/day prednisone or equivalent.\n- Patients with unresolved adverse events (other than alopecia) from prior anticancer therapy that have not resolved to grade ≤1 or baseline.\n- Patients with positive hepatitis B or hepatitis C antibody.\n- Patients with other clinically active infectious liver disease.\n- Patients who are positive for HIV.\n- Patients with active cardiovascular disease.\n- Patients with interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis.\n- Patients with a history of haemoptysis (≥2.5 mL of bright red blood per episode) within 1 month prior to enrolment.\n- Patients with evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).\n- Patients with current or recent (within 10 days before enrolment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and clostazol.\n- Patients with current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for >2 weeks prior to enrolment.\n- Patients with serious, non-healing wound, active ulcer, or untreated bone fracture.\n- Patients who had a core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment.\n- Patients who had major surgery or significant traumatic injury within 28 days prior to enrolment.\n- Patients who had placement of a vascular access device within 2 days prior to prior to enrolment.\n- Patients with a history of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrolment.\n- Patients with clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.\n- Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.\n- Patients with concurrent or prior malignancy other than the disease under study.\n- Patients with uncontrolled illness.\n- History of hypersensitivity to either the drug substance or any excipients in amivantamab, lazertinib and/ or bevacizumab.\n- Prior chemotherapy.\n- Prior treatment with bevacizumab or another anti-angiogenic inhibitor.\n- Prior treatment with a MET/EGFR-targeting antibody.\n- Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.\n- Women who are pregnant or in the period of lactation."}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR) at 12 weeks according to RECIST v1.1","definition_or_measurement_approach":"ORR measured at 12 weeks according to RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"- Duration of Response (DoR)\n- Progression-free survival (PFS) according to RECIST v1.1\n- Disease control rate (DCR) according to RECIST v1.1\n- Overall survival (OS)\n- Safety and tolerability (CTCAE v5.0)","definition_or_measurement_approach":"DoR, PFS and DCR assessed according to RECIST v1.1; OS measured as time to death; safety and tolerability assessed using CTCAE v5.0"}

Netherlands

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

27

Number Of Sites

1

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

03-10-2024

Processing Time Days

16

Number Of Sites

3

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

27

Number Of Sites

7

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

27

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

ETOP IBCSG Partners Foundation

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Switzerland

Third parties

• {"country":"Switzerland","full_name":"Centre Hospitalier Universitaire Vaudois","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Frontier Science Foundation-Hellas","duties_or_roles":"10,11","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"15 (Packaging, labeling, release and distribution)","organisation_type":"Pharmaceutical company"}