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

Gastric Cancer Stage IV Clinical Trial

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 Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04592211
• Other study ID #: 4-2020-0544
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 1, 2021
• Est. completion date: May 31, 2023

Study information

• Verified date: August 2021
• Source: Yonsei University
• Contact: Sun Young Rha, MD. Ph.D
• Phone: 82-2-2228-8053
• Email: rha7655[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 71
• Est. completion date: May 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Gastric Cancer Stage IV
• Stomach Neoplasms

Intervention

Drug:
• olaparib+pembrolizumab+paclitaxel
olaparib, 100~200mg, PO, bid, continuous pembrolizumab 200mg, IV, q 3 weeks paclitaxel 175g/m2 IV, q 3 weeks

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival		6 weeks
Primary	dose limiting toxicity		21 days
Secondary	overall response rate		6 weeks