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

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат olaparib+pembrolizumab+paclitaxel
  olaparib, 100\~200mg, PO, bid, continuous Pembrolizumab 200mg, IV, q 3 weeks Paclitaxel 80mg/m2 IV, Q weekly

Первичные конечные точки

• progression free survival [Срок оценки: 6 weeks]
• Dose Limiting Toxicity [Срок оценки: 21 days]

Вторичные конечные точки (1)

• overall response rate [Срок оценки: 6 weeks]

Критерии участия

Критерии включения

• Provided written informed consent for treatment.
• Age ≥ 19 years old
• measurable or evaluable disease based on RECIST 1.1. Lesions
• 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%

Критерии исключения

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Severance Hospital — Seoul

Идентификаторы

NCT: NCT04592211 · 4-2020-0544

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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