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Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04592211
Recruitment Status : Not yet recruiting
First Posted : October 19, 2020
Last Update Posted : August 31, 2021
Information provided by (Responsible Party):
Sun Young Rha, Yonsei University

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
Gastric Cancer Stage IV Drug: olaparib+pembrolizumab+paclitaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 71 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With Homologous Recombination Repair (HRR) Mutation and Microsatellite Stable (MSS).
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : May 31, 2023

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. progression free survival [ Time Frame: 6 weeks ]
  2. dose limiting toxicity [ Time Frame: 21 days ]

Secondary Outcome Measures :
  1. overall response rate [ Time Frame: 6 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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. 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)
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on time of patient's allocation.
  6. Adequate organ function as defined by the following criteria:
  7. A life expectancy of at least 3 months
  8. Is able to swallow and retain orally administered medications
  9. Failed first-line trastuzumab treatment for HER2 positive patients
  10. Highly effective contraception for both male and female subjects if the risk of conception exists.
  11. 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 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)
  3. Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation.
  4. Has received prior radiotherapy within 2 weeks of start of study treatment.
  5. Has received a live vaccine within 30 days prior to the first dose of study drug.
  6. 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.
  7. 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.
  8. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
  9. Has known active CNS metastases and/or carcinomatous meningitis.
  10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, PARP inhibitor and paclitaxel.
  11. Has active autoimmune disease that has required systemic treatment in the past 2 years
  12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  13. Has an active infection requiring systemic therapy.
  14. Has a known history of Human Immunodeficiency Virus (HIV).
  15. 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.
  16. Has an active TB (Bacillus Tuberculosis) with treatment.
  17. Participant has received previous allogenic bone-marrow, tissue/solid organ transplant or double umbilical cord transplantation (dUCBT).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04592211

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Contact: Sun Young Rha, MD. Ph.D 82-2-2228-8053

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Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Contact: Sun Young Rha, Ph.D         
Sponsors and Collaborators
Yonsei University
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Responsible Party: Sun Young Rha, MD, Ph.D, Yonsei University Identifier: NCT04592211    
Other Study ID Numbers: 4-2020-0544
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: August 31, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors