Study of TU2218 in Combination With KEYTRUDA®(Pembrolizumab) in Patients With Advanced Solid Tumors
NCT05784688 · Phase 1, Phase 2 · San Antonio, Texas, United States
- Condition
- Head and Neck Cancer
- Disease stage
- Stage I-IV
- Phase
- Phase 1, Phase 2
- Study type
- DRUG
- Intervention
- TU2218 + KEYTRUDA® (Pembrolizumab)
- Age
- 18 Years to
- Gender
- All
- Sponsor
- TiumBio Co., Ltd.
- Research institution
- TiumBio Co., Ltd.
- Facility
- NEXT Oncology
- Research center
- NEXT Oncology
Summary
This study consists of phase 1b and 2a to evaluate safety, Pharmacokinetics, and efficacy of TU2218 in combination with Pembrolizumab in patients with advanced solid tumors.
Detailed description
The primary objective of phase 1b is to determine the recommended phase 2 dose of the combination (RP2DC) of TU2218 given with pembrolizumab in advanced solid tumors. The primary objective of phase 2a is to evaluate the efficacy of TU2218 administered in combination with pembrolizumab in selected advanced tumors.
Inclusion criteria
1. Male and females ≥18 years of age 2. Life expectancy ≥12 weeks as judged by the Investigator 3. Measurable disease as defined by RECIST v1.1 4. ECOG 0 or 1 5. Able to swallow capsules 6. For Phase 1b and 2a: histologically or cytologically documented advanced unresectable solid tumor for which no effective standard therapy exists, or that has progressed on or not tolerated prior standard therapy. If previously treated with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, PD-1 treatment progression is defined by meeting all of the following criteria: 1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb 2. Has demonstrated clinical progression after anti-PD-1/L1 mAb therapy 3. Progressive disease has been documented within 16 weeks from the last dose of anti-PD-1/L1 mAb 7. For HNSCC cohort in Phase 2a: anti-PD-(L)1 agent-naïve metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) whose tumors express programmed death ligand 1 (PD - L1) \[combined positive score (CPS) ≥1\] as determined by an FDA-approved test Or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy (as applicable). 8. For BTC cohort in Phase 2a: biliary tract cancer that has been locally advanced unresectable or metastatic or not tolerated prior standard first line chemotherapy and second line targeted therapy (as applicable). 9. For CRC cohort in Phase 2a: anti-PD-(L)1 agent-naïve colorectal adenocarcinoma of Proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) subtype, as determined by an FDA-approved test, that has progressed on or not tolerated at least 2 lines of prior standard chemotherapy with biological agents where applicable. Patients with liver metastasis from primary CRC, as confirmed by RESIST v1.1, will be excluded from Phase 2a CRC cohort. 10. Adequate hematological function and coagulation defined by * ANC ≥1,500 cells/μL * Platelet count ≥100,000/μL * Hemoglobin ≥9.0 g/dL (criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin \[≥ approximately 3 months\]) * International normalized ratio ≤1.5 upper limit of normal (ULN) 11. Adequate hepatic and renal function * Total bilirubin ≤1.5 × ULN * AST and alanine aminotransferase (ALT) ≤2.5 × ULN; if liver metastases are present, then ≤5 × ULN is allowed. * Estimated creatinine clearance ≥60 mL/minute according to the Cockcroft Gault formula. 12. Able to understand and to comply with all protocol requirements, instructions, and restrictions. For Phase 2a, willing and able to provide archival tumor samples or undergo biopsy for biomarker testing during screening. 13. QTcF interval ≤470 msec on screening ECG. 14. Normal ejection fraction (within the reference range of the institution). 15. No concomitant anti-cancer treatments, including experimental agents for 5 half-lives for non-biological agents and a minimum of 4 weeks for any biologics prior to the start of treatment. 16. Resolution of any toxicity to maximum Grade 1 (except alopecia and Grade ≤2 neuropathy) prior to the start of treatment. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible. 17. Completion of radiotherapy (palliative or curative) at least 14 days prior to the start of treatment with resolution of any toxicity to maximum Grade 1. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. 18. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) defined as all female after puberty unless they are postmenopausal for at least 1 year or are surgically st
Exclusion criteria
1. Myocardial infarction within 6 months prior to screening, or pericardial effusion 2. History of cardiac or aortic surgery within 12 months 3. Unstable angina pectoris, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis; arterial occlusive disease in the past 12 months 4. Congestive heart failure of New York Heart Association class III/IV 5. Major arrhythmia or abnormalities identified by ECG per Investigator's judgement 6. Uncontrolled hypertension (as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) during the Screening Period. 7. Elevated Troponin I levels (Grade 3) at screening 8. Metastatic disease to the brain or central nervous system, carcinomatous meningitis, massive uncontrolled effusions (pleural, pericardial, peritoneal), and pulmonary lymphangitis 9. Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of TU2218 10. Tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed 11. History of severe bleeding. Unable to stop anticoagulation therapy with heparin, low molecular weight heparin, vitamin K antagonists, anti-platelet agents, or factor Xa inhibitors throughout the study and for at least 28 days post the last dose of study treatment 12. Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation 13. Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels 14. Female participants must not be pregnant or at risk of becoming pregnant during the study. Fertile male and female participants must agree to use a highly effective method of birth control to avoid pregnancy (for female participants a double-barrier method of contraception, for male participants a condom with spermicide) or total abstinence from the time of providing informed consent until at least 30 days after the last dose of TU2218 or until at least 120 days after the last administration of Pembrolizumab, whichever comes later. 15. Female participants who are breastfeeding 16. For Phase 1b and BTC cohort in Phase 2a: discontinued prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137), due to an irAE. 17. For CRC and HNSCC cohorts in Phase 2a: received prior therapy with an anti-PD-1, anti PD-L1, or anti PD-L2 agent or an agent directed to another stimulatory or co inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137). 18. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible. Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention. 19. Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. 20. Has received or planned to receive any live or live-attenuated vaccine (e.g., measles, mumps, rubella or chickenpox) within 30 days prior to the first drug administration and while participating the study. Note: Administration of killed vaccines are allowed. Receipt of mRNA vaccine, includ
Primary outcomes
Phase 1b: To determine the Recommended Phase 2 Dose of the Combination (RP2DC) of TU2218 given with Pembrolizumab in selected advanced solid tumors; Phase 2a: To evaluate the efficacy of TU2218 by evaluating the Overall Response rate (ORR) of TU2218 administered in combination with Pembrolizumab in selected advanced solid tumors
Secondary outcomes
Phase 1b and 2a: To further evaluate the safety and tolerability of TU2218 administered in combination with pembrolizumab.; Phase 1b and 2a: The PK of TU2218 administered in combination with pembrolizumab; Time to Progression (TTP)