Combination therapy for advanced gastric 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.

This study is testing a new combination of treatments for people with advanced stomach cancer to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 71 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Yonsei University (Academic / other)
• Drugs / interventions: trastuzumab, pembrolizumab, prednisone, ramucirumab, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Seoul)
• Trial ID: NCT04592211 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of a combination treatment involving pembrolizumab, olaparib, and paclitaxel for patients with recurrent or advanced gastric and gastro-esophageal junction cancer. Pembrolizumab is an immunotherapy that targets the PD-1 receptor, while olaparib is a PARP inhibitor that works to prevent cancer cell repair. The study aims to evaluate the safety and effectiveness of this combination in patients who have not responded to previous treatments. Participants will be monitored for disease progression and response to therapy based on established criteria.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 19 and older with measurable or evaluable stage IV gastric cancer who have failed first-line trastuzumab treatment.

Not a fit: Patients who have received prior systemic anti-cancer therapy or radiotherapy within two weeks prior to the study may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced gastric cancer who have limited treatment alternatives.

How similar studies have performed: While the combination of these specific agents is being explored in this trial, similar approaches using immunotherapy and targeted therapies have shown promise in other studies.

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. 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).

Where this trial is running

Seoul

• Severance Hospital — Seoul, South Korea (Recruiting)

Study contacts

• Principal investigator: Sun Young Rha, MD.Ph.D — Yonsei Cencer center, Yonsei University Collrge of Medicine
• Study coordinator: Sun Young Rha, MD. Ph.D

Conditions Gastric Cancer Stage IV