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.

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer Stage IV
• Intervention / Treatment: Drug: olaparib+pembrolizumab+paclitaxel

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.

• Study Type: Interventional
• Enrollment (Estimated): 71
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sun Young Rha, MD. Ph.D; Phone Number: 82-2-2228-8053; Email: rha7655@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Sun Young Rha, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olaparib+pembrolizumab+paclitaxel	Drug: olaparib+pembrolizumab+paclitaxel; olaparib, 100~200mg, PO, bid, continuous Pembrolizumab 200mg, IV, q 3 weeks Paclitaxel 80mg/m2 IV, Q weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	progression free survival	6 weeks
Dose Limiting Toxicity	Dose Limiting Toxicity	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	overall response rate	6 weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sun Young Rha, MD.Ph.D, Yonsei Cencer center, Yonsei University Collrge of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Pembrolizumab; Paclitaxel; Olaparib
• Other Study ID Numbers: 4-2020-0544

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No