None listed
Conditions
Interventions
Drug : Single arm: Pembrolizumab 400 mg every 6 weeks (Q6W), trifluridine/tipiracil at 35 or 30 mg/m2 twice daily (BID) for 5 days a week (D1-5, D8-12) with 2 days rest for 2 weeks, followed by a 14-d
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has provided written informed consent for the trial. 2. Is male or female at least 18 years of age on the day of signing informed consent. 3. Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma (systemic metastasis or locally advanced unresectable gastric cancer). 4. Has previously received at least 2 prior regiments (at least 1 cycle per regimen) for advanced disease and were refractory to or unable to tolerate their last prior therapy. 5. Has a life expectancy of at least 3 months. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment (see Appendix 1). 7. Have 1 or more measurable disease as determined by RECIST 1.1. This does not apply to lead-in safety cohort. 8. Is able to take medications orally (i.e. study drug must not be administered via a feeding tube). 9. Has adequate organ function as defined by the following criteria: a. Absolute neutrophil count (ANC) of =1,500/mm3 (=1.5 × 109/L). b. Platelet count =100,000/mm3 (=100 × 109/L). c. Hemoglobin value of =9.0 g/dL d. Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) =3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT =5 × ULN. e. Total serum bilirubin of =1.5 × ULN (except for Grade 1 hyperbilirubinemia due solely to a medical diagnosis of Gilbert’s syndrome). f. Serum creatinine =1.5 mg/dL or creatinine clearance >60 mL/min (either measured value or estimated value using the Cockcroft-Gault equation). 10. Is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures as defined in this study protocol. 11. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days post TAS-102, corresponding to time needed to eliminate any study treatment after the last dose of study treatment and refrain from donating sperm during this period. 12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies.
Exclusion criteria
Exclusion criteria: 1. Has other concurrently active malignancies (with the exception of malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment). 2. Has received prior therapy with TAS-102. 3. Is contraindicated for pembrolizumab and/or TAS-102, or have severe hypersensitivity (=Grade 3) to any of those drugs and/or their excipients. 4. Has any unresolved =Grade 2 toxicity (per CTCAE v5.0) attributed to any prior therapies at the time of enrollment (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity). 5. Has had major surgery within 2 weeks prior to first dose of study interventions. Note: The surgical incision should be fully healed prior to first dose of study treatment. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. 6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e. without evidence of progression by imaging) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 7. Has received radiotherapy for gastric cancer treatment within 2 weeks prior to the first dose of study drugs. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 8. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 9. 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 to the first dose of study drug. 10. Has participated or is currently participating in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. 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. 11. Has a history of uncontrollable or significant cardiovascular disease meeting any of the following: a. myocardial infarction within 12 months before study enrollment. b. uncontrollable angina pectoris within 180 days before study enrollment. c. New York Heart Association (NYHA) Class III or IV congestive heart failure. d. uncontrollable hypertension despite appropriate treatment (e.g. systolic blood pressure =150 mmHg or diastolic blood pressure =90 mmHg lasting 24 hours or more). e. arrhythmia requiring treatment. 12. Has active (significant or uncontrolled) gastrointestinal bleeding. 13. Has active autoimmune disease that has required systemic treatment in the 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, etc.) is not considered a form of systemic treatment and is allowed. 14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneum
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib (Lead-in safety cohort): To evaluate dose-limiting toxicity (DLT) and to determine the recommended Phase 2 dose (RP2D) of pembrolizumab in combination with TAS-102.;Objective response rate (ORR) according to RECIST 1.1;Progression-free survival (PFS), disease control rate (DCR), and duration of response (DOR) as assessed per RECIST 1.1, and overall survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of pembrolizumab in combination with TAS-102. | — |
Countries
Korea, Republic of
Contacts
Public ContactSun Young Rha
Yonsei University Health System, Severance Hospital
Outcome results
None listed