Back to resultsNivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study. (da VINci)
Primary Purpose
Gastric Cancer
Status
Recruiting
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
OTSGC-A24
Nivolumab
Ipilimumab
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer focused on measuring Nivolumab, Ipilimumab, OTSGC-A24
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed inoperable or metastatic gastric cancer that has failed or demonstrated intolerance to standard therapy - which includes platinum or fluoropyrimidine or taxane based chemotherapy.
- Patients must have measurable disease.
- Age ≥ 21 years
- ECOG performance status (PS) of 0 to 1
- Life expectancy at least 3 months
Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- Creatinine <1.5x normal institutional limits
- Patients must be HLA-A*24:02
- Patients must have recovered (< grade 1) from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients receiving any other investigational products
- Patients who have previously received prior nivolumab or PD-/L1 blockade therapy
- Active autoimmune disease requiring disease-modifying therapy.
- Concurrent systemic steroid therapy higher than physiologic dose (equivalent of prednisolone 10mg daily)
- Any form of active primary or secondary immunodeficiency.
- History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.
- Serious non healing wound and peptic ulcer disease
- Previous history of intestinal perforation
- Symptomatic central nervous system (CNS) metastasis
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic >160 mmHg and/or diastolic >100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (≤ 6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid, and active viral hepatitis.
- Women who are breast-feeding or pregnant are excluded from this study.
Sites / Locations
- National University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
(Arm A) OTSGC-A24 + nivolumab
(Arm B) OTSGC-A24 + nivolumab + ipilimumab
Arm Description
Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14 each 28 day cycle (q28d) for up to 24 months.
Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14. Ipilimumab 1mg/kg (IV) will be administered q6w (i.e. C1D1, C2D15, C3D1 …) of each 28 day cycle for up to 24 months.
Outcomes
Primary Outcome Measures
Adverse Event and Adverse Drug Reaction
Response Rate
Secondary Outcome Measures
Rate of induction of specific CTL response
Progression-free Survival
Overall Survival
Full Information
NCT ID
NCT03784040
First Posted
December 20, 2018
Last Updated
April 5, 2019
Sponsor
National University Hospital, Singapore
Collaborators
OncoTherapy Science, Inc., Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03784040
Brief Title
Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.
Acronym
da VINci
Official Title
da VINci Study (OTSGC-A24 Therapeutic Peptide Vaccine + Ipilimumab + Nivolumab) Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2019 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore
Collaborators
OncoTherapy Science, Inc., Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary hypothesis is that cancer vaccine can convert non-immunogenic gastric cancer into immunogenic phenotype susceptible to PD1 inhibition. This would lead to an improved radiological response rate and favorable immune contexture for immune checkpoint blockade
Detailed Description
Primary Objectives
Safety cohorts: To evaluate the safety of OTSGC-A24 and nivolumab (+ ipilimumab) in patients with refractory gastric cancer.
Arm A: To determine the objective response rate of OTSGC-A24 and nivolumab in advanced gastric cancer.
Arm B: To determine the objective response rate of OTSGC-A24 and nivolumab + ipilimumab in advanced gastric cancer.
Secondary Objectives
To compare the difference in objective response rates between Arm A and Arm B
To compare the tumoral immune contexture and PDL-1 expression before treatment, after OTSGC-A24, and after nivolumab (+ ipilimumab) in combination with OTSGC-A24.
To determine the serum cytotoxic T-cell response using enzyme-linked immunospot assay (ELISPOT) in PBMC.
To determine the progression-free survival (PFS) and overall survival (OS) of Arm A and Arm B.
To evaluate the effect of OTSGC-A24 and nivolumab + ipilimumab on clinical and immune PD markers.
Evaluate the effects of treatment on peripheral T-cell phenotypic profiles with epitope-specificities by coupling mass cytometric analyses with highly-multiplexed peptide-MHC tetramer staining technology.
Identify potential biomarkers for treatment response and mechanisms of secondary resistance by studying gene expression profiles and phenotypic/functional markers of tumour and infiltrating immune cells.
End Points - Efficacy
The endpoints for efficacy are:
Induction of specific CTL response after vaccination
Response rate
Progression-free survival
Overall survival End Points - Safety
The endpoints for safety are:
• overall adverse events observed, treatment-related adverse events, and category (eg percentage of patients with any-grade treatment-related adverse events and grade 3-4 treatment-related adverse events).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer
Keywords
Nivolumab, Ipilimumab, OTSGC-A24
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
(Arm A) OTSGC-A24 + nivolumab
Arm Type
Experimental
Arm Description
Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14 each 28 day cycle (q28d) for up to 24 months.
Arm Title
(Arm B) OTSGC-A24 + nivolumab + ipilimumab
Arm Type
Experimental
Arm Description
Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14. Ipilimumab 1mg/kg (IV) will be administered q6w (i.e. C1D1, C2D15, C3D1 …) of each 28 day cycle for up to 24 months.
Intervention Type
Drug
Intervention Name(s)
OTSGC-A24
Intervention Description
OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Intervention Description
OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
Primary Outcome Measure Information:
Title
Adverse Event and Adverse Drug Reaction
Time Frame
3 years
Title
Response Rate
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Rate of induction of specific CTL response
Time Frame
3 years
Title
Progression-free Survival
Time Frame
3 years
Title
Overall Survival
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed inoperable or metastatic gastric cancer that has failed or demonstrated intolerance to standard therapy - which includes platinum or fluoropyrimidine or taxane based chemotherapy.
Patients must have measurable disease.
Age ≥ 21 years
ECOG performance status (PS) of 0 to 1
Life expectancy at least 3 months
Patients must have normal organ and marrow function as defined below:
Absolute neutrophil count (ANC) ≥ 1,500/mcL
Platelets ≥ 100,000/mcL
Total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
Creatinine <1.5x normal institutional limits
Patients must be HLA-A*24:02
Patients must have recovered (< grade 1) from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Patients receiving any other investigational products
Patients who have previously received prior nivolumab or PD-/L1 blockade therapy
Active autoimmune disease requiring disease-modifying therapy.
Concurrent systemic steroid therapy higher than physiologic dose (equivalent of prednisolone 10mg daily)
Any form of active primary or secondary immunodeficiency.
History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.
Serious non healing wound and peptic ulcer disease
Previous history of intestinal perforation
Symptomatic central nervous system (CNS) metastasis
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic >160 mmHg and/or diastolic >100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (≤ 6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid, and active viral hepatitis.
Women who are breast-feeding or pregnant are excluded from this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Peng Yong
Phone
(65) 6779 5555
Email
Wei_Peng_Yong@nuhs.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Peng Yong
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Peng Yong
Phone
(65) 6779 5555
Email
Wei_Peng_Yong@nuhs.edu.sg
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16782930
Citation
Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006 Jun 20;24(18):2903-9. doi: 10.1200/JCO.2005.05.0245.
Results Reference
background
PubMed Identifier
18089789
Citation
Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007 Dec 15;67(24):11601-11. doi: 10.1158/0008-5472.CAN-07-3243.
Results Reference
background
PubMed Identifier
11441938
Citation
Janunger KG, Hafstrom L, Nygren P, Glimelius B; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in gastric cancer. Acta Oncol. 2001;40(2-3):309-26. doi: 10.1080/02841860151116385.
Results Reference
background
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Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.
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