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

NCT03784040 | Unknown Phase 1 DMC

• 2 other identifiers: GA01/03/182018/00422
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Gastric Cancer

Keywords

Nivolumab; Ipilimumab; OTSGC-A24

Outcome Measures

Primary Outcomes (2)

• Adverse Event and Adverse Drug Reaction

  3 years

• Response Rate

  3 years

Secondary Outcomes (3)

• Rate of induction of specific CTL response

  3 years

• Progression-free Survival

  3 years

• Overall Survival

  3 years

Study Arms (2)

(Arm A) OTSGC-A24 + nivolumab

EXPERIMENTAL

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.

Drug: OTSGC-A24; Drug: Nivolumab

(Arm B) OTSGC-A24 + nivolumab + ipilimumab

EXPERIMENTAL

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.

Drug: OTSGC-A24; Drug: Nivolumab; Drug: Ipilimumab

Interventions

OTSGC-A24 DRUG

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.

(Arm A) OTSGC-A24 + nivolumab; (Arm B) OTSGC-A24 + nivolumab + ipilimumab

Nivolumab DRUG

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.

(Arm A) OTSGC-A24 + nivolumab; (Arm B) OTSGC-A24 + nivolumab + ipilimumab

Ipilimumab DRUG

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.

(Arm B) OTSGC-A24 + nivolumab + ipilimumab

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• OncoTherapy Science, Inc.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Related Publications (3)

• 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.

  PMID: 16782930 BACKGROUND

• 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.

  PMID: 18089789 BACKGROUND

• 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.

  PMID: 11441938 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Wei Peng Yong

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Peng Yong

CONTACT

(65) 6779 5555; Wei_Peng_Yong@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 21, 2018
• Study Start: February 21, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)