Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fibrolamellar Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Vaccines

Immunomodulating Agents

Nivolumab

Poly ICLC

Ipilimumab

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

Immunologic Factors

1. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and Day 1 of cycle 2, 3, 4 and 5 (priming phase). Boost vaccinations: every 3 cycles beginning C6D1. For Cohort A-(Initial) only: Patients with FLC cancer with no prior checkpoint inhibitor therapy treatment.
2. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and on Day 1 of cycle 2, 3 and 4 (priming phase). Boost vaccinations: every 3 cycles beginning C5D1.

   * Cohort A-(Expansion): Patients with FLC cancer with no prior checkpoint inhibitor treatment.
   * Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment.
   * Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
3. Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5mg Poly-ICLC

DNAJB1-PRKACA peptide vaccine

1. Cohort A (Initial): Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 2-5 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 6.
2. Cohort A (Expansion), B and C: Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 1-4 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 5.
3. Drug: 3mg/kg and 480mg IV

1. Cohort A (Initial): Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 2, 3, 4 and 5 of the study, every 3 weeks of the priming phase.
2. Cohort A (Expansion), B and C: Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 1, 2, 3 and 4 of the study, every 3 weeks of the priming phase.
3. Drug: 1mg/kg IV

Colleen Apostol, RN

Marina Baretti, MD

Mark Yarchoan, MD

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and to assess the T-cell response.

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD8 cells after vaccination at 10 weeks compare to pre-vaccination baseline.

Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD4 T cells after vaccination at 10 weeks compare to pre-vaccination baseline.

ORR is defined as the number of patients 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.

Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date of disease progression or death is documented per RECIST 1.1. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.

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 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.

PFS is defined as number of months from the date of first treatment until first documented local progression 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. Estimation based on the Kaplan-Meier curve.

OS will be measured from date of first 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.

Bristol-Myers Squibb

Fibrolamellar Cancer Foundation

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Herbal and Botanical

Mitoguazone

Poly I-C

Carboxymethylcellulose Sodium

Laxatives

Cathartics

Antiviral Agents

Cola

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

Neoantigen Vaccine with Poly-ICLC adjuvant

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.

Retifanlimab

Nilofer Azad, MD

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).

Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colon and Pancreatic Ductal Cancer

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

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).

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

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.

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.

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.

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.

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.

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.

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.

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.

Incyte Corporation

Hematinics

Liver Extracts

The HCC patients will be treated firstly by Microwave Ablation, and then treated by courses of Neoantigen Vaccines.

The HCC patients will be treated only by Microwave Ablation.No vaccine will be used.

HCC (3cm≤D ≤5 cm, fewer than three tumors) patients were treated with Microwave Ablation and 7 courses of neoantigen-based DC vaccines.The first neoantigen-based DC vaccine injection will take place up to 30 days following the completion of Microwave Ablation. The day of the first vaccine injection will be referred to as Day 1.The schedule of vaccination is Day 1, Day 8, Day 15, Day 22, Day 50, Day78, Day106.

Neoantigen Vaccines

ALL the HCC patients will be treated by Microwave Ablation.

Microwave Ablation

Jie Yu, Doctor

Li Chen, Doctor

Ping Liang, Doctor

This is a single institution, open-label, multi-arm, pilot study of a personalized neoantigen-based dendritic cell (DC) vaccine combined with microwave ablation in subjects with Hepatocellular Carcinoma (HCC). Patients with HKLC stage IIa HCC are eligible for enrollment. In this study, the investigators are looking at the safety, feasibility of the personalized neoantigen-based DC vaccine combined with microwave ablation as well as the T cell immune response to the vaccine.

A Study Combining Personalized Neoantigen-based Dendritic Cell Vaccine With Microwave Ablation for the Treatment of Hepatocellular Carcinoma

A Study to Assess the Safety, Feasibility, and Immunogenicity of Personalized Neoantigen-based Dendritic Cell Vaccine in Combination With Microwave Ablation to Treat Hepatocellular Carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma	NCT04248569	Fibrolamellar H...	DNAJB1-PRKACA p... Nivolumab Ipilimumab	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colon and Pancreatic Ductal Cancer	NCT04799431	Pancreatic Canc... Colorectal Canc...	Neoantigen Vacc... Retifanlimab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma	NCT04248569	Fibrolamellar H...	DNAJB1-PRKACA p... Nivolumab Ipilimumab	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Study Combining Personalized Neoantigen-based Dendritic Cell Vaccine With Microwave Ablation for the Treatment of Hepatocellular Carcinoma	NCT03674073	Hepatocellular ... Liver Cancer, A...	Neoantigen Vacc... Microwave Ablat...	18 Years -	Chinese PLA General Hospital

Spots Global Cancer Trial Database for neoantigen vaccines