Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.

Gastric Cancer Clinical Trial

— 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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03784040
• Other study ID #: GA01/03/18
• Secondary ID: 2018/00422
• Status: Recruiting
• Phase: Phase 1
• Start date: February 21, 2019
• Est. completion date: March 1, 2024

Study information

• Verified date: April 2019
• Source: National University Hospital, Singapore
• Contact: Wei Peng Yong
• Phone: (65) 6779 5555
• Email: Wei_Peng_Yong[@]nuhs.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Primary Objectives

1. Safety cohorts: To evaluate the safety of OTSGC-A24 and nivolumab (+ ipilimumab) in patients with refractory gastric cancer.

2. Arm A: To determine the objective response rate of OTSGC-A24 and nivolumab in advanced gastric cancer.

3. Arm B: To determine the objective response rate of OTSGC-A24 and nivolumab + ipilimumab in advanced gastric cancer.

Secondary Objectives

1. To compare the difference in objective response rates between Arm A and Arm B

2. To compare the tumoral immune contexture and PDL-1 expression before treatment, after OTSGC-A24, and after nivolumab (+ ipilimumab) in combination with OTSGC-A24.

3. To determine the serum cytotoxic T-cell response using enzyme-linked immunospot assay (ELISPOT) in PBMC.

4. To determine the progression-free survival (PFS) and overall survival (OS) of Arm A and Arm B.

5. To evaluate the effect of OTSGC-A24 and nivolumab + ipilimumab on clinical and immune PD markers.

6. 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.

7. 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Patients must have measurable disease.

3. Age = 21 years

4. ECOG performance status (PS) of 0 to 1

5. Life expectancy at least 3 months

6. 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

7. Patients must be HLA-A*24:02

8. Patients must have recovered (< grade 1) from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.

9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients receiving any other investigational products

2. Patients who have previously received prior nivolumab or PD-/L1 blockade therapy

3. Active autoimmune disease requiring disease-modifying therapy.

4. Concurrent systemic steroid therapy higher than physiologic dose (equivalent of prednisolone 10mg daily)

5. Any form of active primary or secondary immunodeficiency.

6. History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.

7. Serious non healing wound and peptic ulcer disease

8. Previous history of intestinal perforation

9. Symptomatic central nervous system (CNS) metastasis

10. 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.

11. Women who are breast-feeding or pregnant are excluded from this study.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• OTSGC-A24
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.
• Nivolumab
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.
• Ipilimumab
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.

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (3)

Lead Sponsor	Collaborator
National University Hospital, Singapore	Bristol-Myers Squibb, OncoTherapy Science, Inc.

Country where clinical trial is conducted

Singapore, 

References & Publications (3)

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. — View Citation

Janunger KG, Hafström 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Event and Adverse Drug Reaction		3 years
Primary	Response Rate		3 years
Secondary	Rate of induction of specific CTL response		3 years
Secondary	Progression-free Survival		3 years
Secondary	Overall Survival		3 years