Trial Title:
Study of TU2218 in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
NCT ID:
NCT05784688
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TU2218 + Pembrolizumab
Description:
TU2218: Orally administered Pembrolizumab: Intravenously administered
Arm group label:
TU2218 + Pembrolizumab Phase 1b
Arm group label:
TU2218 + Pembrolizumab in Biliary Tract Cancer (BTC) expansion cohort Phase 2a
Arm group label:
TU2218 + Pembrolizumab in Cervical Cancer (CC) expansion cohort Phase 2a
Arm group label:
TU2218 + Pembrolizumab in Colorectal Cancer (CRC) expansion cohort Phase 2a
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. The
main purpose of phase 1b is to determine the RP2DC of TU2218 and Pembrolizumab while the
main purpose of phase 2a is to evaluate the antitumor efficacy of TU2218 in combination
with Pembrolizumab in 3 different selected tumor type cohorts.
Criteria for eligibility:
Criteria:
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 12 weeks from the last dose of
anti-PD-1/L1 mAb
7. For CC cohort in Phase 2a: cervical squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of the cervix that has received at least one line of therapy
for advanced or metastatic disease that included anti-PD-(L)1 inhibitor, and that
has progressed on or not tolerated prior standard therapy
8. For BTC cohort in Phase 2a: anti-PD(L)1 agent naïve cholangiocarcinoma that has
progressed on 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 that has
progressed on or not tolerated at least 2 lines of prior standard chemotherapy with
biological agents where applicable (anti-angiogenic treatment with bevacizumab or
ziv-aflibercept or ramucirumab, anti-epidermal growth factor receptor treatment with
cetuximab or panitumumab for KRAS/NRAS/BRAF WT, encorafenib for V600E mutation
positive, anti-HER2 treatment for HER2-amplified, etc.).
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.
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
sterile (hysterectomy or bilateral oophorectomy or tubal ligation)
2. A WOCBP who has a negative serum pregnancy test within 3 days of the first
administration of study treatment and agrees to follow contraceptive guidance
during the treatment period and for at least 30 days after the last dose of
TU2218 or until at least 120 days after the last dose of Pembrolizumab,
whichever comes later
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 CC 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 BTC and CRC 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,
including Coronavirus disease-2019 (COVID-19) vaccine, within 7 days prior to drug
administration of Day 1 and during the first 2 cycles of study treatment will not be
allowed
21. 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
22. Has had an allogeneic tissue/solid organ transplant
23. Received prior treatment targeting the signaling pathway of TGF-Beta
24. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study treatment
25. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years Note: Participants with basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding
carcinoma in situ of bladder, that have undergone potentially curative therapy are
not excluded
26. Has severe hypersensitivity (Grade ≥3) to Pembrolizumab and/or any of its excipients
27. Has an active autoimmune disease or history of autoimmune disease, except vitiligo,
hypothyroidism or resolved childhood asthma/atopsy, that has required systemic
treatment in past 2 years (i.e., with use of disease modifying agents,
corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed
28. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
29. Has an active infection requiring systemic antibiotic therapy
30. Active and clinically significant bacterial, fungal, or viral infection, including
known history of hepatitis B virus (HBV), known hepatitis C virus (HCV), known human
immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness.
Note: No testing for HBV, HCV, and HIV is required unless mandated by local healthy
authority
31. Unable or unwilling to stop use of strong inhibitors of cytochrome P450 (CYP)1A2,
2C8 and 3A4, and strong inhibitors of P-gP and breast cancer resistance protein
(BCRP) at least 8 days prior to and during study treatment in all Phase 1b dose
escalation cohorts
32. Unable or unwilling to stop use of gastric pH elevating agents including proton pump
inhibitors, H2-receptor antagonists and antacids at least 8 days prior to and during
study treatment in all Phase 1b dose escalation cohorts
33. Has a history or current evident of any condition, therapy, or laboratory
abnormality, or other circumstance that might confound the results of the study or
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating Investigator
34. Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study
35. Known history, or suspected hypersensitivity to any excipients of the clinical study
treatments
36. Any other serious medical condition which in the Investigator's opinion would
preclude safe participation in the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
NEXT Oncology
Address:
City:
San Antonio
Zip:
78229-3307
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anthony Tolcher
Phone:
210-580-9500
Facility:
Name:
Hope Cancer Center
Address:
City:
Tyler
Zip:
75701
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arielle Lee
Phone:
903-592-6152
Facility:
Name:
Medical Oncology
Address:
City:
Spokane
Zip:
99208
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arvind Chaudhry
Phone:
509-462-2273
Start date:
March 10, 2023
Completion date:
December 2028
Lead sponsor:
Agency:
TiumBio Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
TiumBio Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05784688
