Biomarker study of PDR001 in combination with MCS110 in gastric cancer

Not Applicable

Completed

Conditions: Neoplasms

Registration Number: KCT0003237

Lead Sponsor: Seoul National University Hospital

Brief Summary: 1. Efficacy - Response rate Among 10 patients, 9 patients were available for tumor response. No CR or PR was observed. Two patients(22.2%) had stable disease and 7(77.8%) had progressive disease. DCR(CR+PR+SD) was 22.2%. - Survival The median PFS and OS were 1.87 months(95% CI 1.43-2.28) and 4.27 months (2.3-6.23) 2. Overall Conclusion MCS110 plus PDF001 showed a modest clinical outcomes and manageable toxicities. Further planned translational studies will suggest a promising biomarkers to predict the efficacy and toxicity of MCS441 and PDF001 and to be helpful to select the patients.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 10

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 ß-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, including any of the following:
1) clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade >2), uncontrolled hypertension or clinically significant arrhythmia
2) QTcF>470 msec on screening ECG
3) Acute myocardial infarction or unstable angina pectoris <3 months prior to study entry
4. Active autoimmune disease or a documented history of autoimmune disease within 3 years before screening, including the following:
1) A documented history of inflammatory bowel disease (< 3 years)
2) Recent active diverticulitis (<12months)
3) Patients with vitiligo, resolved childhood asthma/atopy, and type I DM, residual hypothyroidism due to an autoimmune condition and only requiring hormone replacement are not excluded
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 (even though anti-HCV Ab is positive, if HCV-RNA is not detectable, this subject should not be 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 intersititnal lung disease or drug-induced interstital 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. Any previous steroid or immunosuppressive therapy must be stopped at least 7 days before start of study treatment. Topical, inhaled, nasal and ophthalmic steroids are not prohibited.
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 (mediastinoscopy. Insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery)
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 hemotologic toxicity or = CTCAE Gr3 non-hemotologic 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