Non-small Cell Lung Cancer
Conditions
Interventions
Drug : ivonescimab, Pembrolizumab
[Monotherapy Part] The subjects will receive 20 mg / kg Q3W ivonescimab. A fixed dose of 3200 mg for ivonescimab should be used for patients >= 160 kg.
[Phase III Pa
Sponsors
Noam Frey
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Monotherapy Part : 1. Voluntarily sign a written informed consent form (ICF) 2. Age >= 18 years old at the time of enrollment 3. ECOG performance status score of 0 or 1 4. Expected life expectancy >= 3 months 5. Advanced or metastatic NSCLC, according to American Joint Committee on Cancer (AJCC) 8th edition with no standard of care treatment options available 6. Adequate Organ Function: Phase 3 Part : 1. Voluntarily sign a written informed consent form (ICF) 2. Age >= 18 years old at the time of enrollment 3. ECOG performance status score of 0 or 1 4. Expected life expectancy >= 3 months 5. Metastatic (Stage IV) NSCLC, according to American Joint Committee on Cancer (AJCC) 8th edition 6. Histologically or cytologically confirmed squamous or non-squamous NSCLC. 7. Patients must have a TPS or TC for PD-L1 expression prior to randomization. The TPS/TC score can be obtained from an existing report or be performed any time before study entry using archival tissue utilizing a clinical assay approved/cleared by local health authorities. If site is unable to perform a TPS/TC score locally, then the site should provide tumor tissue (fresh or archival) for central TPS/TC determination. 8. At least one measurable noncerebral lesion according to RECIST 1.1. 9. No prior systemic treatment for metastatic NSCLC. Patients receiving adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease. 10. Adequate Organ Function: 11. Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
Exclusion criteria
Exclusion criteria: Monotherapy Part : 1. Concurrent enrollment in another clinical study 2. Received systemic therapy within 4 weeks prior to enrollment; received nonspecific immunomodulatory therapy (eg, interleukin, interferon, thymus peptide, tumor necrosis factor) within 2 weeks prior to enrollment, excluding IL-11 for the treatment of thrombocytopenia. 3. Imaging during the screening period shows that the patient has: a. Radiologically documented evidence of major blood vessel invasion or encasement by cancer b. Radiographic evidence of intratumor cavitation 4. Symptomatic CNS metastases, CNS metastasis >=1.5 cm, CNS radiation within 2 weeks prior to enrollment, potential need for CNS radiation within the first cycle, or leptomeningeal disease 5. Other prior malignancy 6. Active autoimmune or lung disease requiring systemic therapy (eg, with disease- modifying drugs, prednisone >=10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment 7. History of major diseases before enrollment 8. Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrollment, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted. 9. Severe infection within 4 weeks prior to enrollment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to enrollment. 10. Major surgical procedures or serious trauma within 4 weeks prior to enrollment, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment. 11. History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment 12. Current hypertension after oral antihypertensive therapy 13. Presence of pleural effusions, pericardial effusions, or ascites that is clinically symptomatic or requires repeated drainage 14. History of noninfectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease 15. Active or prior history of inflammatory bowel disease 16. Known history of HIV 17. Current use of systemic corticosteroids (>=10 mg daily prednisone or equivalent) 18. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation 19. History of hepatitis B or active hepatitis B, patients with active hepatitis C 20. Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies interest of the subject to participate, in the opinion of the treating investigator 21. Patient is breastfeeding or plans to breastfeed during the study 22. Other conditions where the investigator considers the patient inappropriate for enrollment Phase 3 Part : 1. Histologic or cytopathologic evidence of the presence of small cell lung carcinoma. 2. Known actionable genomic alterations (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], ROS1, and BRAF V600E) for which first-line approved therapies are available. For non-squamous histology patients, actionable driver mutation testing results are required before randomization. 3. Has received any prior therapy for NSCLC in the metastatic setting Note: Local therapy (plus/minus cor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| [Monotherapy Part] - Safety assessment: dose limiting toxicities (DLTs), incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results - PK characteristics: ivonescimab serum drug concentrations profiles [Phase III Part] - OS - PFS assessed by investigator based on RECIST v1.1 | — |
Countries
Belgium, Canada, China, France, Germany, Greece, Ireland, Italy, Japan, Mexico, Poland, Serbia, Spain, Sweden, Turkey, UK, US
Contacts
Public ContactToshiki Hiraga
CMIC Co., Ltd.
Outcome results
None listed