Study of TU2218 in Combination With KEYTRUDA®(Pembrolizumab) in Patients With Advanced Solid Tumors
A Phase 1b/2a Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of TU2218, an Oral TGFβR Serine/Threonine Kinase Inhibitor, Administered in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
2 other identifiers
interventional
140
2 countries
11
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2023
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 20, 2023
CompletedStudy Start
First participant enrolled
March 10, 2023
CompletedFirst Posted
Study publicly available on registry
March 27, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
March 30, 2025
February 1, 2025
3.7 years
February 20, 2023
March 25, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Phase 1b: To determine the Recommended Phase 2 Dose of the Combination (RP2DC) of TU2218 given with Pembrolizumab in selected advanced solid tumors
At least 1 Dose limiting toxicity (DLT) during Cycle1
During the first 21-day period (Cycle 1)
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
ORR is defined as the proportion of patients with a best overall response of Complete response (CR) or Partial response (PR) according to RECIST v1.1 Efficacy analyses will be performed on both PP and ITT Efficacy Analysis Sets.
24 weeks
Secondary Outcomes (7)
Phase 1b and 2a: To further evaluate the safety and tolerability of TU2218 administered in combination with pembrolizumab.
approximately 13 months
Phase 1b and 2a: The PK of TU2218 administered in combination with pembrolizumab
Cycle 1 (each cycle is 21 days)
Time to Progression (TTP)
over 24 weeks
Duration of Response (DoR)
over 24 weeks
Disease Control Rate (DCR)
over 24 weeks
- +2 more secondary outcomes
Study Arms (4)
Phase 1b: TU2218 + KEYTRUDA® (Pembrolizumab) in solid tumor
EXPERIMENTALTU2218 orally and KEYTRUDA® (Pembrolizumab) intravenously administered daily for two weeks followed by one week to determine RP2DC.
Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in Biliary Tract Cancer (BTC)
EXPERIMENTALTU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)
Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in Head and Neck Squamous Cell Carcinoma (HNSCC)
EXPERIMENTALTU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)
Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in ColoRectal Cancer (CRC)
EXPERIMENTALTU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)
Interventions
TU2218: Orally administered KEYTRUDA® (Pembrolizumab): Intravenously administered
Eligibility Criteria
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
- +15 more criteria
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
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- TiumBio Co., Ltd.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (11)
NEXT Oncology
San Antonio, Texas, 78229-3307, United States
Hope Cancer Center
Tyler, Texas, 75701, United States
Medical Oncology
Spokane, Washington, 99208, United States
CHA University Bundang Medical Center
Seongnam, South Korea
Seoul National University Bundang Hospital
Seongnam, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital
Seoul, South Korea
The Catholic University of Korea Seoul St. Mary Hospital
Seoul, South Korea
The Catholic University of Korea St. Vincent's Hospital
Suwon, South Korea
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
TU2218
TiumBio Co., Ltd.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 20, 2023
First Posted
March 27, 2023
Study Start
March 10, 2023
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2028
Last Updated
March 30, 2025
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will not share
We will make our final decision after EOP2 meeting.