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Biomarker Study of PDR001 in Combination With MCS110 in Gastric Cancer

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ClinicalTrials.gov Identifier: NCT03694977
Recruitment Status : Recruiting
First Posted : October 3, 2018
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Yung-Jue Bang, Seoul National University Hospital

Brief Summary:

<Background>

  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.

<Trial objectives> 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.


Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: MCS110/PDR001 combination Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: MCS110/PDR001 combination
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarker Study of PDR001 in Combination With MCS110 in Gastric Cancer
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: MCS110/PDR001 combination Drug: MCS110/PDR001 combination
MCS110 7.5mg/kg iv since 1st cycle PDR001 300 mg iv since 2nd cycle Q 3weeks




Primary Outcome Measures :
  1. Identification of potential biomarkers of MCS110 in combination with PDR001 [ Time Frame: 3weeks ]
    The current study explores potential biomarkers of MCS110 in combination with PDR001 that predict tumor response in the tumor tissue and blood of patients with gastric cancer.


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: 6weeks ]
    According to RECIST v1.1 criteria

  2. Immune-related response rate [ Time Frame: 6weeks ]
    According to RECIST v1.1 criteria

  3. Progression-free survival [ Time Frame: 6weeks ]
    Time from randomization until disease progression or death

  4. Duration of response [ Time Frame: 6weeks ]
    Time from documentation of tumor response to disease progression

  5. Disease control rate [ Time Frame: 6weeks ]
    The percentage of patients who have achieved complete response, partial response and stable disease

  6. Overall survival [ Time Frame: 3months ]
    Time from randomization until death from any cause

  7. Safety as measured by number and grade of toxicity events [ Time Frame: 3weeks ]
    According to CTCAE v4.03



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03694977


Contacts
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Contact: Yung-Jue Bang, MD, PhD 82-2-2072-2390 bangyj@snu.ac.kr

Locations
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Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yung-Jue Bang    82-2-2072-2390    bangyj@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
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Principal Investigator: Yung-Jue Bang Seoul National University Hospital

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Responsible Party: Yung-Jue Bang, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03694977     History of Changes
Other Study ID Numbers: H-1710-062-893
First Posted: October 3, 2018    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yung-Jue Bang, Seoul National University Hospital:
Gastric Cancer

Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases