Advanced Solid TumorPhase 1/2NCT05204862
Phase 1/2 Study of TU2218 Alone and in Combination With Checkpoint Inhibitors in Patients With Advanced Solid Tumors
A Phase 1/2 study testing TU2218 and Anti-PD-1 antibody in people with Advanced Solid Tumor, run by TiumBio Co., Ltd. at 3 sites in 2 countries.
Trial summary
This study consists of Part A for monotherapy and Part B for combination therapy to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy of TU2218 in patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- TU2218 and Anti-PD-1 antibody
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 2 Dec 2021to 30 Sep 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females at least 18 years of age at the time of consent (ie, screening), or according to local regulatory requirement if the legal age for consenting for study participation is more than 18 years.
- Life expectancy ≥12 weeks as judged by the Investigator.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; except for Phase1a that can enroll patients with either measurable and/or non-measurable disease.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Able to swallow capsules.
- Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, or standard therapy has failed (Phase 1a).
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- Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, and for which standard therapy containing an anti-PD-(L)1 agent has failed after an initial response or stabilization of at least 4-month duration (Phase 1b and 2a).
- Adequate hematological function, coagulation defined by:
- Absolute neutrophil count ≥1,500 cells/μL
- Platelet count ≥100,000/μL
- Hemoglobin ≥9.0 g/dL
- International normalized ratio <1.5 × the upper limit of normal (ULN)
- Adequate hepatic and renal functions defined by:
- Total bilirubin ≤1.5 × ULN
- AST and ALT ≤3 × ULN; if liver metastases are present, then ≤5 × ULN is allowed
- Estimated creatinine clearance >60 mL/min according to the Cockcroft-Gault formula
- Able to understand and to comply with all protocol requirements, instructions, and restrictions.
- QT interval corrected using Fridericia's formula (QTcF) interval ≤460 msec on screening ECG.
- Normal ejection fraction (within the reference range of the institution).
- A washout period of 4 weeks for any biologic material and a minimum of 5 half-lives for any chemotherapy is required prior to the start of treatment with resolution of any toxicity to maximum Grade 1 (except alopecia)
- Completion of radiotherapy at least 14 days prior to the start of treatment with resolution of any toxicity to maximum Grade 1
- Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study treatment. For the purpose of this study, female patients of childbearing potential are defined as all female after puberty unless they are postmenopausal for at least 1 year, or are surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation)
Who cannot join
- Myocardial infarction within 6 months prior to screening, or pericardial effusion.
- History of cardiac or aortic surgery within 6 months prior to screening.
- 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 judgment.
- Uncontrolled hypertension (as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) during the screening period.
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- Elevated troponin 1 levels (Grade 3) at screening or known to have persistently elevated brain natriuretic peptide.
- Active and clinically significant bacterial, fungal, or viral infection, including active or known history of hepatitis B virus (defined as hepatitis B surface antigen [HbsAg] reactive), or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid [qualitative] is detected), known human immunodeficiency virus or acquired immunodeficiency syndrome related illness. However, an inactive hepatitis B virus carrier can be enrolled
- Current or history of interstitial pneumonitis.
- Uncontrolled metastatic disease to the brain or central nervous system, massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement that is at the discretion of the Investigator. Note: Pleural effusion should be defined by Investigator's discretion.
- Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
- Received prior treatment targeting the signaling pathway of TGF-β.
- 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, antiplatelet agents, or factor Xa inhibitors throughout the study and for at least 28 days after the last administration of study treatment.
- Regular use of aspirin (>325mg/day) or other non-steroidal anti-inflammatory drugs with antiplatelet activity or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol within 10 days of first administration 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.
- Active infection requiring systemic antibiotic therapy.
- Receipt of any live vaccine or live-attenuated vaccine within 30 days prior to the first drug administration and while participating the study.
- Unable to unwilling to stop use of strong inhibitors of CYP1A2, CYP2C8, and CYP3A4, and strong inhibitors of P-gp and BCRP at least 8 days prior to study entry (Day 1) or within all dose escalation cohorts.
- Unable or unwilling to stop use of gastric pH elevating agents including proton pump inhibitors, H2-recpetor antagonists and antacide at least 8 days prior to study entry (Day 1) or within all dose escalation cohorts.
- Unwilling to stop use of herbal supplements or traditional herbal medicines.
- Known substance abuse concurrent treatment with non-permitted drugs.
- Known history, or suspected hypersensitivity to any excipients of the clinical study drugs.
- Undergone major surgeries within 28 days of first dosing, or have a planned surgery during the study period.
- Female patients who are breastfeeding.
- Female patients must not be pregnant or at risk to become pregnant during the study. Fertile male and female patients must agree to use an effective barrier method of birth control to avoid pregnancy (for female patients a double-barrier method of contraception, for male patients a condom with spermicide) or total abstinence from the time of providing informed consent until 30 days after the last administration of TU2218.
- Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
- For Anti PD1 antibody combination therapy part:
- Unable to stop chronic systemic steroid therapy or any other immunosuppressive mediacation
- Use of oral, inhaled, or topical corticosteroid, at doses > 10mg/day prednisolone or equivalent and the dose must be stable over 4 weeks prior to Day1 of Cycle1.
- Active autoimmune disease or history of autoimmune disease, except vitiligo, hypothyroidism, or resolved childhood asthma/atropy
- Known tolerance to an anti-PD(L)1 agent during prior exposure
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
South Korea2 sites, 2 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Asan Medical Center
Seoul, 05505
United States1 site, 1 recruiting
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
About this study
Official title: A Phase 1/2 Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TU2218, an Oral TGFβR Inhibitor, Administered Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
This study consists of Part A for monotherapy and Part B for combination therapy to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy of TU2218 in patients with advanced solid tumors. The main purpose of Phase 1 is to determined the recommended Phase 2 dose (RP2D) of TU2218 and the main purpose of Phase 2 is to evaluate the antitumor activity of TU2218 at RP2D.
- Conditions
- Advanced Solid Tumor
- Being tested
- TU2218, Anti-PD-1 antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TU2218Drug
orally administered
Anti-PD-1 antibodyDrug
Intravenously administered
| Study group | Role | What they receive |
|---|---|---|
| TU2218 Phase 1a | Experimental | Escalating doses of TU2218 orally administered daily for two weeks followed by one week of rest for up to 21-day cycles Receives: Drug: TU2218 |
| TU2218 Food Effect | Experimental | TU2218 orally administered at a one dose level below MTD under fasting condition on -Day 2, followed by the same dose orally administered with meals on -Day 1 and then continued under fasted condition for two weeks followed by one week of rest for up to 21-day cycles Receives: Drug: TU2218 |
| TU2218 + Anti-PD-1 antibody Phase 1b | Experimental | Escalating doses of TU2218 in combination with anti-PD-1 antibody up to 21-day cycles Receives: Drug: TU2218; Drug: Anti-PD-1 antibody |
| TU2218 Phase 2a | Experimental | TU2218 at a RP2D orally administered daily for two weeks followed by on week of rest for up to 21-day cycles Receives: Drug: TU2218 |
| TU2218 + Anti-PD-1 antibody Phase 2b | Experimental | TU2218 at a RP2DC in combination with anti-PD-1 antibody up to 21-day cycles Receives: Drug: TU2218; Drug: Anti-PD-1 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose (MTD) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)
The MTD is determined as DLTs.
Measured: From the beginning of Cycle 1 through Cycle 2 (each cycle is 21 days)
Phase 2: Overall Response rate (ORR) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)
ORR is defined as the proportion of patients who have a PR and CR.
Measured: 24 weeks
Secondary outcomes (9)
Incidence of treatment-emergent AEs
TEAE is defined as treatment-emergent changes in clinical laboratory values, ECG, vital signs, ECOG performance scores, and physical examination findings.
Measured: approximately 13 months
Peak Plasma Concentration (Cmax) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Cmax is defined as the maximum observed concentration of the drug in plasma.
Measured: Cycle 1
Area under the plasma concentration versus time curve (AUC) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
AUC is defined as the definite integral of a curve that describes the variation of a drug concentration in plasma as a function of time.
Measured: Cycle 1
Terminal half-life (t1/2) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Half-life is defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Measured: Cycle 1
Clearance (CL) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
CL is defined as the volume of plasma from which a substance is completely removed per unit time.
Measured: Cycle 1
Duration of Response (DoR)
DoR is measured from the date of documented response to the date of first progression of disease or the date of death due to any cause, whichever is earlier.
Measured: over 24 weeks
Progression Free Survival (PFS)
PFS is defined as the time from the date of first study treatment to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or iRECIST.
Measured: over 24 weeks
Overall Survival (OS)
OS is determined from the date of first study treatment until death due to any cause.
Measured: Date of First Study Treatment to Death from Any Cause (up to 24 months)
Clinical benefit rate (CBR)
CBR is defined as the proportion of patients with the best overall response as CR, PR or SD (lasting at least 24 weeks)
Measured: over 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start2 Dec 2021
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TiumBio Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- TU2218, Study director, TiumBio Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05204862
- Sponsor's protocol ID
- TUC1PI-01
- Status last verified
- Mar 2023
- First submitted
- 21 Dec 2021
- Last updated
- 3 Apr 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We will make our final decision after EOP2 meeting.
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TU2218, an Oral TGFβR Inhibitor, Administered Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT05204862
- Acronym / sponsor ID
- TUC1PI-01
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- TiumBio Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 2 Dec 2021 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 24 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study consists of Part A for monotherapy and Part B for combination therapy to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy of TU2218 in patients with advanced solid tumors. The main purpose of Phase 1 is to determined the recommended Phase 2 dose (RP2D) of TU2218 and the main purpose of Phase 2 is to evaluate the antitumor activity of TU2218 at RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| TU2218 Phase 1a | Experimental | Drug: TU2218Escalating doses of TU2218 orally administered daily for two weeks followed by one week of rest for up to 21-day cycles |
| TU2218 Food Effect | Experimental | Drug: TU2218TU2218 orally administered at a one dose level below MTD under fasting condition on -Day 2, followed by the same dose orally administered with meals on -Day 1 and then continued under fasted condition for two weeks followed by one week of rest for up to 21-day cycles |
| TU2218 + Anti-PD-1 antibody Phase 1b | Experimental | Drug: TU2218, Drug: Anti-PD-1 antibodyEscalating doses of TU2218 in combination with anti-PD-1 antibody up to 21-day cycles |
| TU2218 Phase 2a | Experimental | Drug: TU2218TU2218 at a RP2D orally administered daily for two weeks followed by on week of rest for up to 21-day cycles |
| TU2218 + Anti-PD-1 antibody Phase 2b | Experimental | Drug: TU2218, Drug: Anti-PD-1 antibodyTU2218 at a RP2DC in combination with anti-PD-1 antibody up to 21-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Males and females at least 18 years of age at the time of consent (ie, screening), or according to local regulatory requirement if the legal age for consenting for study participation is more than 18 years.
- Life expectancy ≥12 weeks as judged by the Investigator.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; except for Phase1a that can enroll patients with either measurable and/or non-measurable disease.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Able to swallow capsules.
Key exclusion criteria (33 listed)
- Myocardial infarction within 6 months prior to screening, or pericardial effusion.
- History of cardiac or aortic surgery within 6 months prior to screening.
- 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 judgment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TU2218orally administered | Drug | TU2218 + Anti-PD-1 antibody Phase 1b, TU2218 + Anti-PD-1 antibody Phase 2b, TU2218 Food Effect, TU2218 Phase 1a, TU2218 Phase 2a |
| Anti-PD-1 antibodyIntravenously administered | Drug | TU2218 + Anti-PD-1 antibody Phase 1b, TU2218 + Anti-PD-1 antibody Phase 2b |
Primary outcome
Phase 1: Maximum Tolerated Dose (MTD) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)
Time frame: From the beginning of Cycle 1 through Cycle 2 (each cycle is 21 days)
The MTD is determined as DLTs.
Phase 2: Overall Response rate (ORR) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)
Time frame: 24 weeks
ORR is defined as the proportion of patients who have a PR and CR.
9 secondary outcomes
Incidence of treatment-emergent AEs
Time frame: approximately 13 months
Peak Plasma Concentration (Cmax) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Time frame: Cycle 1
Area under the plasma concentration versus time curve (AUC) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Time frame: Cycle 1
Terminal half-life (t1/2) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Time frame: Cycle 1
Clearance (CL) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody
Time frame: Cycle 1
Duration of Response (DoR)
Time frame: over 24 weeks
Progression Free Survival (PFS)
Time frame: over 24 weeks
Overall Survival (OS)
Time frame: Date of First Study Treatment to Death from Any Cause (up to 24 months)
Clinical benefit rate (CBR)
Time frame: over 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2023.
- Individual participant dataSharing planned: No. We will make our final decision after EOP2 meeting.
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
TU2218 study director
TiumBio Co., Ltd.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TU2218 and Anti-PD-1 antibody in people with Advanced Solid Tumor, run by TiumBio Co., Ltd. at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact TiumBio Global http://www.tiumbio.com/en/ (82-31-600-1500, nce401_tu2218@tiumbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum Tolerated Dose (MTD) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B) (time frame: From the beginning of Cycle 1 through Cycle 2 (each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2023.