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
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 77
1.Male/female participants who are at least 19 years of age with histologically confirmed diagnosis of advanced or metastatic gastric or GEJ adenocarcinoma.
2.A male participant must agree to use a contraception during the treatment period and for at least 120 days and refrain from donating sperm during this period.
3.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.
4.The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5.Have measurable or evaluable disease based on RECIST 1.1.
6.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7.Have adequate organ function as defined in Table 3.
8.Has life expectancy of at least 3 months.
9.Is able to swallow and retain orally administered medications.
10.Failed first-line trastuzumab treatment for HER2 positive patients.
11.Left ventricular ejection fraction (LVEF) =50% measured by multiple-gated acquisition scan (MUGA) or electrocardiogram (ECHO).
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.
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 previously received olaparib or other PARP inhibitors.
8.Has a history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or characteristics of MDS/AML.
9.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
10.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
11.Has known active CNS metastases and/or carcinomatous meningitis.
12.Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients, PARP inhibitor and paclitaxel.
13.Has active autoimmune disease that has required systemic treatment in the past 2 years.
14.Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
15.Has an active infection requiring systemic therapy.
16.Has a known history of Human Immunodeficiency Virus (HIV).
17.Has an active of Hepatitis B or known active Hepatitis C virus infection.
18.Has an active TB (Bacillus Tuberculosis) with treatment.
19.May potentially influence the results of this trial, interfere with subject’s participation in overall duration of the study, or has history of or current evidence of conditions, treatment, or abnormal laboratory values that is deemed to be not in the best interests of the subject to participate in the trial in the opinion of treating investigator.
20.Has received more than 2nd lines of systemic chemotherapy.
21.Is mentally ill or has substance abuse disorder that may affect subject’s compliance with requirements of the study.
22.Is pregnant or breastfeeding, or is planning to become pregnant within the study period starting from screening visit to 120 days after the last dose of study treatment.
23.Is otherwise not appropriate to enroll in this study as determined by the investigator.
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase Ib (Dose Escalation): To determine the maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of olaparib for the combination of pembrolizumab and paclitaxel;Phase II (Dose Expansion): To evaluate the treatment effect of olaparib, pembrolizumab, and paclitaxel combination on progression free survival (PFS)
- Secondary Outcome Measures
Name Time Method To evaluate the treatment effect on overall survival (OS);To evaluate the treatment effect on overall response rate (ORR) and disease control rate (DCR);To evaluate the treatment effect on progression-free survival (PFS) rate at 24 weeks;To assess the safety and tolerability of triplet combination therapy and maintenance treatment with doublet.