Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: olaparib+pembrolizumab+paclitaxel
|
Drug: olaparib+pembrolizumab+paclitaxel
olaparib, 100~200mg, PO, bid, continuous pembrolizumab 200mg, IV, q 3 weeks paclitaxel 175g/m2 IV, q 3 weeks
|
Outcome Measures
Primary Outcome Measures
- progression free survival [6 weeks]
- dose limiting toxicity [21 days]
Secondary Outcome Measures
- overall response rate [6 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Provided written informed consent for treatment.
-
Age ≥ 19 years old
-
measurable or evaluable disease based on RECIST 1.1. Lesions
-
tumors with NGS evidence of somatic HRR mutations (harbor known or suspected deleterious mutations in BRCA1, BRCA2, ATM, or other HRR-genes: BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) and MSS stauts (detected by IHC: MLH1, MSH2, MSH6, PMS2 or Promega PCR kit)
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on time of patient's allocation.
-
Adequate organ function as defined by the following criteria:
-
A life expectancy of at least 3 months
-
Is able to swallow and retain orally administered medications
-
Failed first-line trastuzumab treatment for HER2 positive patients
-
Highly effective contraception for both male and female subjects if the risk of conception exists.
-
Left ventricular ejection fraction (LVEF) ≥50%
Exclusion Criteria:
-
A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
-
Has received 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 (eg, CTLA-4, OX 40, CD137)
-
Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation.
-
Has received prior radiotherapy within 2 weeks of start of study treatment.
-
Has received a live vaccine within 30 days prior to the first dose of study drug.
-
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.
-
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.
-
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
-
Has known active CNS metastases and/or carcinomatous meningitis.
-
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, PARP inhibitor and paclitaxel.
-
Has active autoimmune disease that has required systemic treatment in the past 2 years
-
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
-
Has an active infection requiring systemic therapy.
-
Has a known history of Human Immunodeficiency Virus (HIV).
-
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.
-
Has an active TB (Bacillus Tuberculosis) with treatment.
-
Participant has received previous allogenic bone-marrow, tissue/solid organ transplant or double umbilical cord transplantation (dUCBT).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Severance Hospital | Seoul | Korea, Republic of |
Sponsors and Collaborators
- Yonsei University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 4-2020-0544