Clinical Trials /

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

NCT04592211

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 4-2020-0544
  • NCT ID: NCT04592211

Conditions

  • Gastric Cancer Stage IV

Interventions

DrugSynonymsArms
olaparib+pembrolizumab+paclitaxelolaparib+pembrolizumab+paclitaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
olaparib+pembrolizumab+paclitaxelExperimental
  • olaparib+pembrolizumab+paclitaxel

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. 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression free survival
Time Frame:6 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:overall response rate
Time Frame:6 weeks
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Yonsei University

Last Updated

October 16, 2020