Study of TU2218 in Combination With KEYTRUDA®(Pembrolizumab) in Patients With Advanced Solid Tumors

Recruiting now · Phase 1/Phase 2

Conditions studied: Solid Tumor, Biliary Tract Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Cancer

In brief

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.

Key facts

Study ID

NCT05784688

Run by

TiumBio Co., Ltd.

People needed

140

Starts

2023-03-10

Expected to finish

2028-12-01

Last updated by the study team

2025-03-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male and females ≥18 years of age
• Life expectancy ≥12 weeks as judged by the Investigator
• Measurable disease as defined by RECIST v1.1
• ECOG 0 or 1
• Able to swallow capsules
• 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:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb
• Has demonstrated clinical progression after anti-PD-1/L1 mAb therapy
• Progressive disease has been documented within 16 weeks from the last dose of anti-PD-1/L1 mAb
• 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).
• 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).
• 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.
• 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)
• 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.
• 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.
• QTcF interval ≤470 msec on screening ECG.
• Normal ejection fraction (within the reference range of the institution).
• 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.

You may not qualify if…

• Myocardial infarction within 6 months prior to screening, or pericardial effusion
• History of cardiac or aortic surgery within 12 months
• Unstable angina pectoris, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis; arterial occlusive disease in the past 12 months
• Congestive heart failure of New York Heart Association class III/IV
• Major arrhythmia or abnormalities identified by ECG per Investigator's judgement
• Uncontrolled hypertension (as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) during the Screening Period.
• Elevated Troponin I levels (Grade 3) at screening
• Metastatic disease to the brain or central nervous system, carcinomatous meningitis, massive uncontrolled effusions (pleural, pericardial, peritoneal), and pulmonary lymphangitis
• Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of TU2218
• Tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed
• 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
• Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation
• Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels
• 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.
• Female participants who are breastfeeding
• 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.
• 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).
• 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.
• 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.
• 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, including Coronavirus disease-2019 (COVID-19) vaccine, within 7 days prior to drug administration on Day 1 and during the first 2 cycles of study treatment will not be allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent

Where it is running

• The Catholic University of Korea St. Vincent's Hospital — Suwon, South Korea (enrolling)
• Seoul National University Hospital — Seoul, South Korea (enrolling)
• Severance Hospital — Seoul, South Korea (enrolling)
• The Catholic University of Korea Seoul St. Mary Hospital — Seoul, South Korea (enrolling)
• CHA University Bundang Medical Center — Seongnam, South Korea (enrolling)
• Seoul National University Bundang Hospital — Seongnam, South Korea (enrolling)
• Asan Medical Center — Seoul, South Korea (enrolling)
• Samsung Medical Center — Seoul, South Korea (enrolling)
• Hope Cancer Center — Tyler, Texas, United States
• Medical Oncology — Spokane, Washington, United States
• NEXT Oncology — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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