pembrolizumab, olaparib, recurrent/advanced gastric and gastro-esophageal junction(gej) cancer

Conditions: Gastric Cancer Stage IV

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.

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.

Eligibility criteria:
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).