Patients with Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with mutations in a gene called epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2). Cancer NSCLC harboring activating EGFR or HER2 kinase domain mutations
Conditions
Interventions
All participants will receive the study drug. Depending on the dose group to which they e assigned, participants will take a dose consisting of 4, 6, or 8 pills of the study drug, furmonertinib (each
Sponsors
Syneos Health UK Limited
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form 2. Age =18 years at time of signing Informed Consent Form 3. Ability to comply with the study protocol, in the investigator’s judgment 4. Measurable disease per RECIST v1.1 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Life expectancy of = 12 weeks 7. Adequate hematologic and organ function within 14 days prior to initiation of study treatment 8. For women of childbearing potential (WOCBP): Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs 9. For men who are not surgically sterile: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm 10. Patients with a history of treated CNS metastases or new asymptomatic CNS metastases detected at screening 11. Histologically or cytologically documented, locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy 12. Consent to provide tumor tissue specimen (paraffin-embedded tissue block or 15 serial-cut slides) 13. Disease that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable; or for whom a clinical trial of an investigational agent is a recognized standard of care 14. Documented radiologic disease progression during or after the last systemic antitumor therapy before the first dose of the investigational product (furmonertinib) 15. For patients with EGFR mutations sensitive to osimertinib, the patient must have received osimertinib prior to study enrollment in regions where osimertinib is approved, including the US Stage 1 Dose Escalation and Backfill Cohorts Inclusion Criteria: 16. Documented validated results from local testing of blood or tumor tissue confirming the presence of an EGFR Exon 20 insertion mutation, HER2 Exon 20 insertion mutation, or EGFR activating mutation (including Exon 19 and Exon 21 mutations such as G719X, Exon 19 deletion, L858R, L861Q) or EGFR T790M mutation 17. For patients with NSCLC with EGFR Exon 20 insertion mutations or HER2 Exon 20 insertion mutations, the patient must have experienced disease progression (during or after treatment) or have intolerance to treatment with platinum-based chemotherapy 18. For patients with NSCLC with EGFR activating mutations other than Exon 20 insertion mutations, the patient must have experienced disease progression (during or after treatment) with the standard of care EGFR TKI Stage 2 Cohort 1 Inclusion Criteria: 19. Documented validated results from either local testing of blood or tumor tissue confirming the presence of EGFR Exon 20 insertion mutations 20. The patient must have experienced disease progression (during or after treatment) or have intolerance to treatment with platinum-based chemotherapy Stage 2 Cohort 2 Inclusion Criteria: 21. Documented validated results from either local testing of blood or tumor tissue confirming the presence of HER2 Exon 20 Insertion Mutations 22. The patient must have experienced disease progression (during or after treatment) or have intolerance to treatment with platinum-based chemotherapy Stage 2 Cohort 3 Inclusion Criteria: 23. Documented validated results from either local testing of blood or tumor tissue confirming the presence of an EGFR activating mutation (including Exon 19 and Exon 21 mutations such as G719X, Exon 19 deletion, L858R, L861Q) o
Exclusion criteria
Exclusion criteria: 1. Inability or unwillingness to swallow pills 2. Inability to comply with study and follow-up procedures 3. Malabsorption syndrome or other condition that would interfere with enteral absorption 4. Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently 5. Severe acute or chronic infections 6. In the setting of a pandemic or epidemic, screening for active infections should be considered according to local or institutional guidelines or those of applicable professional societies 7. Previous interstitial lung disease (ILD), drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy; or having the clinical manifestations of suspected ILD. 8. History of or active clinically significant cardiovascular dysfunction 9. Mean resting corrected QT interval (QTcF) > 470 msec, obtained from triplicate ECGs, using the screening clinic ECG machine derived QTcF value. 10. Clinically significant prolonged QT interval or other arrhythmia or clinical status considered by investigators that may increase the risk of prolonged QT interval or current use of the drugs that may lead to prolonged QT interval 11. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium = ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. 12. Significant traumatic injury or major surgical procedure within 4 weeks prior to Day 1 of Cycle 1. 13. Patients with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease or any active bowel inflammation (including diverticulitis) 14. Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of furmonertinib, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications 15. Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 3 weeks or five half-lives prior to initiation of furmonertinib, whichever is shorter, or endocrine therapy within 2 weeks prior to initiation of furmonertinib 16. Radiation therapy (other than palliative radiation to bony metastases and radiation to CNS metastases as described above) as cancer therapy within 4 weeks prior to initiation of furmonertinib 17. Palliative radiation to bony metastases within 2 weeks prior to initiation of furmonertinib 18. Adverse events from prior anti-cancer therapy that have not resolved to Grade = 1 except for alopecia or Grade = 2 peripheral neuropathy 19. History of other malignancy within 3 years prior to screening, with the exception of patients with a negligible risk of metastasis or death and/or treated with expected curative outcome 20. Pregnant, breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of furmonertinib 21. Known or suspected allergy to furmonertinib or other components of its preparation 22. Use of a potent CYP3A4 inhibitor within 7 days prior to the first dose of investigational product or a potent CYP3A4 inducer within 21 days prior to the first dose of furmonertinib 23. Use of an herbal medicine within 2 weeks prior to the first dose of furmo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (AEs) including DLTs, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) during the study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Confirmed objective response rate (ORR), defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients. Confirmation of the response is based on two consecutive assessments, at least 28 days apart, as determined by investigator assessment and blinded independent central review (BICR) assessment using RECIST v1.1 2. Duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and depth of response (DpR) evaluated by investigator assessment and by BICR per RECIST v1.1 3. Overall survival (OS) 4. Central nervous system (CNS) confirmed ORR (CNS ORR) and DOR (CNS DOR) via RECIST v1.1 by BICR 5. Change from baseline in safety-related clinical laboratory test results 6. Plasma concentrations of furmonertinib and its major metabolite (AST5902) at specified timepoints 7. Change from baseline in patient-reported symptoms and their impact on functioning and health-related quality of life, and the overall burden of side effects, as measured by the European Organization for Research and Treatment of Cancer Quality of Life Core 30 Questionnaire (EORTC QLQ-C30) and EORTC QLQ-LC13, and Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC SAQ) 8. Correlation of PK with primary, secondary, exploratory endpoints in patients treated with furmonertinib 9. Change in tumour tissue gene profile at baseline, during treatment, and at disease progression 10. Consistency and change of ctDNA gene profile in the peripheral blood at baseline, during treatment, and disease progression samples 11. EGFR mutation status in ctDNA in peripheral blood or possible changes in resistant gene profile at baseline, during treatment, and at disease progression | — |
Countries
Australia, Japan, Spain, United Kingdom
Outcome results
None listed