Uncommon / Compound EGFR mutated non-small cell lung cancer
Conditions
Interventions
Experimental Arm
Amivantamab is administered either intravenously (1,050 mg for = 80 kg) or subcutaneously (1,600
mg for = 80 kg). For intravenous
administration, Cycle 1 is given in split doses on Da
for subcutaneous
administration, dosing occurs on Days 1, 8, 15, and 22 of
Cycle 1. From Cycle 2 onwards, both formulations are
administered biweekly on Days 1 and 15.
Lazertinib is administered oral
Sponsors
Yamamoto Nobuyuki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients aged >= 18 years at the time of informed consent. 2. Patients who have provided written informed consent after receiving a full explanation of the study protocol prior to enrollment. 3. Patients with histologically or cytologically confirmed non-small cell lung cancer (NSCLC). 4. Patients with non-squamous NSCLC who are unresectable and classified as clinical stage IIIB, IIIC, IV, or have postoperative recurrence or recurrence after definitive chemoradiotherapy. 5. Patients diagnosed with single uncommon or compound EGFR gene mutations based on molecular testing of cytology, biopsy, surgical, or blood specimens. 1) Single uncommon EGFR mutation: Mutations in EGFR exons 18 - 21 excluding Exon 19 deletion and Exon 21 L858R point mutation. Note: Patients with Exon 20 insertion mutations and/or T790M mutations are excluded. 2) Compound EGFR mutation: Patients with uncommon EGFR mutations (excluding Exon 20 insertions) concurrently detected with other EGFR-related mutations. This also includes patients with uncommon EGFR mutations co-occurring with Exon 19 deletions or Exon 21 L858R mutations. 6. Patients with no prior systemic chemotherapy for advanced or recurrent NSCLC. 1) Patients with postoperative recurrence who received adjuvant chemotherapy are eligible if >= 24 weeks have passed since the last dose of any chemotherapy (platinum-doublet, targeted therapy, or immune checkpoint inhibitors). 2) Patients with recurrence after definitive chemoradiotherapy are eligible if >= 24 weeks have passed since the last dose of durvalumab or the final day of radiotherapy, whichever is later. 7. At the time of registration, patients must meet the following washout periods from prior therapies or interventions: 1) Thoracic surgery (including thoracotomy or VATS): >= 4 weeks 2) Palliative radiotherapy: >= 2 weeks 3) Blood transfusion or hematopoietic growth factor administration: >= 2 weeks 8. Patients with no symptomatic brain metastases. 9. ECOG Performance Status of 0 or 1. 10. Patients with at least one measurable lesion or non-measurable but evaluable lesion based on RECIST v1.1. 11. Laboratory values within the following ranges within 14 days prior to enrollment (same weekday allowed): 1) Absolute neutrophil count: >= 1,500 / mm^3 2) Hemoglobin: >= 9.0 g/dL 3) Platelet count: >= 75,000 / mm^3 4) AST: = 90% on room air
Exclusion criteria
Exclusion criteria: 1.Patients with active double cancers (synchronous malignancies). 2.Patients with uncontrolled malignant pleural effusion, pericardial effusion, or ascites. 3.Patients with symptomatic brain metastases. 4.Patients with active or prior leptomeningeal disease. 5.Patients with untreated spinal cord compression. 6.Patients with uncontrolled tumor-related pain. 7.Patients with localized infections requiring intervention or active systemic infections. 8.Patients with active hepatitis B, active hepatitis C requiring treatment, or active HIV infection. 9.Patients with interstitial lung disease (ILD). 10.Patients with intractable nausea and vomiting, difficulty swallowing the study drug formulation, or a significant history of bowel resection that may impair adequate absorption of lazertinib or doxycycline/minocycline. 11.Patients with heart failure, hypokalemia, or congenital long QT syndrome. 12.Patients with severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diathesis, deemed inappropriate for study participation by the investigator. 13.Patients with a history of clinically significant cardiovascular disease. 14.Patients with a known hypersensitivity to afatinib, amivantamab, or lazertinib. 15.Any other condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (by blinded independent central review; BICR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS) Progression-free survival (PFS; investigator-assessed) Objective response rate (ORR; by blinded independent central review [BICR] and investigator-assessed) Duration of response (DoR; BICR and investigator-assessed) PFS by mutation status (BICR and investigator-assessed)* ORR by mutation status (BICR and investigator-assessed)* Safety | — |
Contacts
Public ContactKoji Takeda
West Japan Oncology Group
Outcome results
None listed