Biomarker Study of PDR001 in Combination With MCS110 in Gastric Cancer

• Status: Unknown status
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

Summary

1. Current status of treatment options in advanced gastric cancer.

• The cytotoxic chemotherapy, usually fluoropyrimidine + platinum combination regimen is current standard of care. In case of HER2(+) gastric cancer, the addition of trastuzumab on top of cytotoxic chemotherapy is standard of care.

• In second-line setting, the cytotoxic chemotherapy in combination with Ramucirumab improved the patients' survival compared with cytotoxic chemotherapy alone.

• There are few treatment options for gastric cancer patients who have been treated with more than two lines of palliative chemotherapy. Patients with good performance status even after failure to 2 kinds of palliative chemotherapy still need the active anticancer treatment options. Therefore, this is the high unmet medical need.

2. Current status of immunotherapy development in gastric cancer

3. The importance of tumor microenvironment

4. The role of polarized macrophage in TME

5. The role of polarized macrophage in gastric cancer

6. Potential of combination of PD1 inhibitor and CSF-1 inhibitor

Based on these rationales, we hypothesized that the combination of PD1 inhibitor and CSF1R inhibitor might be synergistic in gastric cancer. However, the exact in vivo immune modulation by each inhibitor has not been revealed so far. Therefore, we will conduct this "biomarker study of PDR001 in combination with MCS110 in gastric cancer" to see the biologic dynamic modulation with MCS110 and combination (MCS110/PDR001) and to see preliminary efficacy signal with this combination.

Primary objective: To see biomarker changes (PDL1, TAM, TIL) by MCS110 monotherapy and MCS110/PDR001 combination (To see the biomarker changes by MCS110 monotherapy at first, then, by MCS110/PDR001 combination in gastric cancer) Secondary objective: To see preliminary efficacy (ORR, irRR, PFS, DOR, DCR, OS) and safety. Phase: Phase 2Accepts Healthy Volunteers? No

Details

• Lead Sponsor: Seoul National University Hospital
• Treatments: Spartalizumab

Criteria

Inclusion Criteria:

1. Signed written informed consent

2. Male or female patient, age ≥ 20 years

3. Pathologically confirmed unresectable or recurrent gastric cancer

4. Patients who have previously treated with at least 2 kinds of palliative chemotherapy

5. Patients must have measurable disease by RECIST 1.1

6. Patients must have easily assessable tumor sites for fresh biopsy

7. ECOG performance status of 0-1

8. Adequate bone marrow, organ function and laboratory parameters:

• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L,

• Hemoglobin (Hgb) ≥ 8 g/dL without transfusions,

• Platelets (PLT) ≥ 75 x 109/L without transfusions,

• AST and ALT ≤ 3 × upper limit of normal (ULN),

• Total bilirubin ≤ 1.5 × ULN, (Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage)

• Creatinine ≤ 1.5 mg/dL

9. Adequate cardiac function:

• QTc interval ≤ 480 ms

10. Negative serum β-HCG test (female patient of childbearing potential only) performed locally within 72 hours prior to first dose.

Exclusion Criteria:

1. Presence of symptomatic CNS metastasis 2 History of severe hypersensitivity reactions to other monoclonal antibodies 3. Impaired cardiac function or clinically significant cardiac disease 4. Active autoimmune disease or a documented history of autoimmune disease within 3 years before screening 5. Active infection, including active tuberculosis requiring systemic antibiotic therapy 6. Known HIV infection 7. Active HBV or HCV infection. HBV carrier without detectable HBV DNA is not excluded 8. Other malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment: completely resected basal cell and squamous cell skin cancers: any malignancy considered to be indolent and that has never required therapy, and completely resected carcinoma in situ of any type 9. Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.

10. History of previous immune-related abnormal reaction or current interstitial lung disease, noninfective interstitial lung disease or drug-induced interstitial pneumonitis

11. Patients who failed immune check point inhibitors which includes PD-1, PDL-1, CTLA4 antagonist and investigational drugs.

12. Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency.

13. Use of any live vaccines against infectious disease within 4 weeks of initiation of study treatment.

14. Major surgery within 2 weeks of the first dose of study treatment 15. Radiotherapy within 2 weeks of the first dose of study treatment, except for palliative radiotherapy to a limited field.

16. Systemic chemotherapy within 3 weeks of the first dose of study treatment. In case of mitomycin Cor nitrosoureas, 4 weeks rest should be needed.

17. Presence of ≥ CTCAE Gr2 hematologic toxicity or ≥ CTCAE Gr3 non-hematologic toxicity(except for alopecia) caused by previous chemotherapy 18. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior start or study drug. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment.

19. Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150 days after the last dose of PDR001 or 90 days after the last dose of MCS110 for patients who stopped PDR001 and continued MCS110 alone for more than 60 days.

21. Sexually active males unless they use a condom during intercourse while taking treatment and for150 days after the last dose of PDR001 or 90 days after the last dose of MCS110 for patients who stopped PDR001 and continued MCS110 alone for more than 60 and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.