Gastric Cancer Stage IV
Conditions
Brief summary
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Olaparib is a potent PARP inhibitor (PARP1, 2, and 3) that is being developed as a monotherapy as well as for combination with chemotherapy, ionizing radiation, and other anti-cancer agents including novel agents and immunotherapy. Paclitaxel is widely used in breast, lung and gastric cancer with every 3-week or weekly cycle. Various targeted anticancer agents have been investigated with paclitaxel and combination with ramucirumab, a monoclonal anti-VEGFR2 antibody, was approved as a 2nd line treatment.
Detailed description
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Olaparib is a potent PARP inhibitor (PARP1, 2, and 3) that is being developed as a monotherapy as well as for combination with chemotherapy, ionizing radiation, and other anti-cancer agents including novel agents and immunotherapy. Paclitaxel is widely used in breast, lung and gastric cancer with every 3-week or weekly cycle. Various targeted anticancer agents have been investigated with paclitaxel and combination with ramucirumab, a monoclonal anti-VEGFR2 antibody, was approved as a 2nd line treatment.
Interventions
DRUGolaparib+pembrolizumab+paclitaxel
olaparib, 100\ 200mg, PO, bid, continuous Pembrolizumab 200mg, IV, q 3 weeks Paclitaxel 80mg/m2 IV, Q weekly
Sponsors
Yonsei University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provided written informed consent for treatment. 2. Age ≥ 19 years old 3. measurable or evaluable disease based on RECIST 1.1. Lesions 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on time of patient's allocation. 5. Adequate organ function as defined by the following criteria: 6. A life expectancy of at least 3 months 7. Is able to swallow and retain orally administered medications 8. Failed first-line trastuzumab treatment for HER2 positive patients 9. Highly effective contraception for both male and female subjects if the risk of conception exists. 10. Left ventricular ejection fraction (LVEF) ≥50%
Exclusion criteria
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation 2. Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation. 3. Has received prior radiotherapy within 2 weeks of start of study treatment. 4. Has received a live vaccine within 30 days prior to the first dose of study drug. 5. Is currently participating in or has participated in a study of an investigational agent including trastuzumab or has used an investigational device within 4 weeks prior to the first dose of study treatment. 6. 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. 7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. 8. Has known active CNS metastases and/or carcinomatous meningitis. 9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, PARP inhibitor and paclitaxel. 10. Has active autoimmune disease that has required systemic treatment in the past 2 years 11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 12. Has an active infection requiring systemic therapy. 13. Has a known history of Human Immunodeficiency Virus (HIV). 14. Has an active of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive and HBV titer \>2000 IU/ml) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. 15. Has an active TB (Bacillus Tuberculosis) with treatment. 16. Participant has received previous allogenic bone-marrow, tissue/solid organ transplant or double umbilical cord transplantation (dUCBT).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | 6 weeks | progression free survival |
| Dose Limiting Toxicity | 21 days | Dose Limiting Toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate | 6 weeks | overall response rate |
Countries
South Korea
Contacts
Primary ContactSun Young Rha, MD. Ph.D
Outcome results
None listed