RECRUITINGPhase 1 / Phase 2INTERVENTIONAL
Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer
An Open Label, Single-Arm, Multi-center Phase Ib/II Study to Evaluate the Efficacy of Paclitaxel in Combination With Pembrolizumab and Olaparib as a Second Line Treatment in Immune Checkpoint Inhibitor-experienced Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer.
About This Trial
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.
Who May Be Eligible (Plain English)
Who May Qualify:
1. Provided written willing to sign a consent form 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. your organs (liver, kidneys, etc.) are working well enough based on blood tests as defined by the following criteria:
6. A expected to live 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%
Who Should NOT Join This Trial:
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 weakened immune system 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 cancer that has spread to the brain and/or carcinomatous meningitis.
9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, PARP inhibitor and paclitaxel.
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
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).
Treatments Being Tested
DRUG
olaparib+pembrolizumab+paclitaxel
olaparib, 100\~200mg, PO, bid, continuous Pembrolizumab 200mg, IV, q 3 weeks Paclitaxel 80mg/m2 IV, Q weekly
Locations (1)
Severance Hospital
Seoul, South Korea