E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with EGFR-mutant advanced NSCLC with progression on previous third generation EGFR TKI |
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E.1.1.1 | Medical condition in easily understood language |
Patients with non-small cell lung cancer that: • Has a change (mutation) in a gene called EGFR • Has spread to other parts of the body during, or after treatment with osimertinib or lazertinib.
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025052 |
E.1.2 | Term | Lung cancer non-small cell stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025044 |
E.1.2 | Term | Lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to assess the efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or lazertinib), in patients with EGFR-mutant advanced NSCLC, who have been previously treated with a third-generation EGFR-TKI in order to provide data on treatment effect and sample size required for a future phase III trial. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate secondary measures of clinical efficacy including progression-free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR).
-To assess the safety and tolerability of the treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or stage IV according to 8th TNM classification - 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. - 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. - 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). - Measurable disease as defined according to RECIST v1.1. - Age ≥18 years. - Eastern Cooperative Oncology Group (ECOG) performance status 0-2. - Life expectancy ≥12 weeks - Adequate haematological, renal and liver function. - Written Informed consent.
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E.4 | Principal exclusion criteria |
- Patients with known small cell lung carcinoma (SCLC) transformation. - 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. - Patients with an active or past medical history of leptomeningeal disease. - 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. - Patients with unresolved adverse events (other than alopecia) from prior anticancer therapy that have not resolved to grade ≤1 or baseline. - Patients with positive hepatitis B or hepatitis C antibody. - Patients with other clinical active infectious liver disease. - Patients who ar positive for HIV. - Patients with active cardiovascular disease. - Patients with interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis. - Patient with a history of haemoptysis (≥2.5 mL of bright red blood per episode) within 1 month prior to enrolment. - Patients with evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). - Patients with current or recent (within 10 days before enrolment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and clostazol. - 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. - Patients with serious, non-healing wound, active ulcer, or untreated bone fracture. - Patients who had a core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment. - Patients who had major surgery or significant traumatic injury within 28 days prior to enrolment. - Patients who had placement of a vascular access device within 2 days prior to prior to enrolment. - Patients with a history of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrolment. - Patients with clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding. - Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure. - Patients with concurrent or prior malignancy other than the disease under study. - Patients with uncontrolled illness. - History of hypersensitivity to either the drug substance or any excipients in amivantamab, lazertinib and/ or bevacizumab. - Prior chemotherapy. - Prior treatment with bevacizumab or another anti-angiogenic inhibitor. - Prior treatment with a MET/EGFR-targeting antibody. - 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. - Women who are pregnant or in the period of lactation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR), investigator assessed, at 12 weeks according to RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
interim analysis (1 year) and final analysis (2 years) |
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E.5.2 | Secondary end point(s) |
1. Duration of response (DoR) 2. Progression-free survival (PFS) according to RECIST v1.1 3. Disease control rate (DCR) according to RECIST v1.1 4. Overall survival (OS) 5. Safety and tolerability (CTCAE v5.0) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
Singapore |
Switzerland |
France |
Italy |
Netherlands |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |