- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04799431
Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colon and Pancreatic Ductal Cancer
May 5, 2023 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Pilot Study of a Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Adenocarcinoma
Phase 1 study evaluating feasibility, safety, and immune response to a personalized neoantigen vaccine combined with retifanlimab for MMR-p mCRC and mPDAC patients with measurable disease following first-line FOLFIRINOX/FOLFOXIRI (FFX).
Study Overview
Status
Withdrawn
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age ≥18 years.
- Have histologically or cytologically - proven cancer of the pancreas or colon.
- Have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
- Measurable disease as per RECIST 1.1.
- Have sufficient and accessible tissue for NGS and immune-phenotyping.
- Have not received any prior systemic therapy in the metastatic setting for PDA or CRC. Patients who have received adjuvant chemotherapy >12 months prior to the diagnosis of metastatic disease may be eligible.
- ECOG performance status 0.
- Life expectancy of greater than 6 months.
- Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
- Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
- Men must use acceptable form of birth control while on study.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
- Is a candidate for definitive surgical resection.
- Is unwilling or unable to undergo standard of care therapy.
- Known history or evidence of brain metastases and/or leptomeningeal spread.
- Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
- Receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days of vaccine treatment.
- Has active autoimmune disease that has required systemic treatment in the past 5 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- Known history or concurrent interstitial lung disease.
- Has a pulse oximetry < 95% on room air.
- Requires the use of home oxygen.
- Infection with HIV or hepatitis B or C.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
- Has been diagnosed with another cancer or myeloproliferative disorder within the past 5 year.
- Has had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
- Has received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
- If at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements.
- Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
- Unwilling or unable to follow the study schedule for any reason.
- Are pregnant or breastfeeding.
- Any radiological or clinical pleural effusions or ascites.
- Any peritoneal involvement by the tumor.
- History of malignant small bowel obstruction.
- On parenteral nutrition.
- Any liver metastasis greater than 3 cm or greater than 5 liver metastases.
- Known or suspected hypersensitivity to Hiltonol.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Neoantigen Vaccine with Poly-ICLC adjuvant and Retifanlimab
All participants receive this intervention.
|
Neoantigen Vaccine with Poly-ICLC adjuvant will be administered on days 1, 8, 15 and 22. 2 to 5 subcutaneous injections will be administered in the upper thighs, arms and/or back. Drug: 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC
Other Names:
500 mg will be administered as a 30 minute IV.
Infusion (-5 min/+15min) on Day 1 of each 28 day cycle every 4 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients who receive at least one dose of personalized neoantigen vaccine
Time Frame: 9 months
|
Percentage of patients that receive at least one dose of personalized neoantigen vaccine in the maintenance setting among the total number of patients who achieved disease response (eligible for vaccine generation).
|
9 months
|
Number of participants experiencing study drug-related toxicities
Time Frame: 2 years
|
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) per RECIST 1.1
Time Frame: 2 years
|
ORR is defined as the number of patients who are administered at least 1 dose of personalized neoantigen vaccine achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study.
CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
2 years
|
Objective Response Rate (ORR) per iRECIST
Time Frame: 2 years
|
ORR is defined as the number of patients who are administered at least 1 dose of personalized neoantigen vaccine achieving a complete response (iCR) or partial response (iPR) based on the Response Evaluation Criteria in Solid Tumors (Immune-related RECIST (iRECIST) at any time during the study.
iCR = disappearance of all target lesions, iPR is =>30% decrease in sum of diameters of target lesions, progressive disease (iPD) is >20% increase in sum of diameters of target lesions, stable disease (iSD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
2 years
|
Disease Control Rate (DCR)
Time Frame: 2 months
|
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 2 months post first vaccination.
CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
2 months
|
Disease Control Rate (DCR)
Time Frame: 6 months
|
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 6 months post first vaccination.
CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
6 months
|
Disease Control Rate (DCR)
Time Frame: 12 months
|
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 12 months post first vaccination.
CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
12 months
|
Progression-free Survival (PFS) per RECIST 1.1
Time Frame: 4 years
|
PFS is defined as the number of months from the date of first personalized vaccine dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause.
Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
4 years
|
Progression-free Survival (PFS) per iRECIST
Time Frame: 4 years
|
PFS is defined as the number of months from the date of first personalized vaccine dose to disease progression (progressive disease [iPD] or relapse from complete response [iCR] as assessed using RECIST 1.1 criteria) or death due to any cause.
Per iRECIST (iPFS) criteria, iCR = disappearance of all target lesions, Partial Response (iPR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (iPD) is >20% increase in sum of diameters of target lesions, Stable Disease (iSD) is <30% decrease or <20% increase in sum of diameters of target lesions.
|
4 years
|
Overall Survival (OS)
Time Frame: 4 years
|
OS will be measured as the number of months from date of first personalized vaccine dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).
Estimation based on the Kaplan-Meier curve.
|
4 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Nilofer Azad, MD, SKCCC at the Johns Hopkins Medical Institution
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 3, 2023
Primary Completion (Actual)
May 3, 2023
Study Completion (Actual)
May 3, 2023
Study Registration Dates
First Submitted
March 11, 2021
First Submitted That Met QC Criteria
March 11, 2021
First Posted (Actual)
March 16, 2021
Study Record Updates
Last Update Posted (Actual)
May 9, 2023
Last Update Submitted That Met QC Criteria
May 5, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Site
- Endocrine System Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Endocrine Gland Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Pancreatic Diseases
- Neoplasms
- Colorectal Neoplasms
- Pancreatic Neoplasms
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Immunologic Factors
- Gastrointestinal Agents
- Interferon Inducers
- Laxatives
- Poly ICLC
- Carboxymethylcellulose Sodium
- Poly I-C
Other Study ID Numbers
- J2114
- 5P50CA062924 (U.S. NIH Grant/Contract)
- IRB00270405 (Other Identifier: Johns Hopkins Medicine Internal Review Board)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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