Vaccine Therapy And Pembrolizumab In Treating Patients With Solid Tumors That Have Failed Prior Therapy

Study Overview

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy

This phase I trial studies the side effects of vaccine therapy and pembrolizumab in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment, that have failed prior therapy, and that cannot be removed by surgery. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving vaccine therapy together with pembrolizumab may be a better treatment in patients with solid tumors.

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of combined p53MVA vaccine (modified vaccinia virus Ankara vaccine expressing p53) and pembrolizumab that are well-tolerated in patients with refractory, tumor protein 53 (p53) over expressing cancer. SECONDARY OBJECTIVES: I. To evaluate clinical response and anti-p53 T cell immune responses. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 subcutaneously (SC) at least 30 minutes later once in weeks 1, 4, and 7. Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19, for a maximum of 7 doses if there are no signs of progressive disease. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Adult Solid Neoplasm
Bladder Carcinoma
Colon Carcinoma
Estrogen Receptor Negative
Head and Neck Squamous Cell Carcinoma
Hepatocellular Carcinoma
HER2/Neu Negative
Melanoma
Non-Small Cell Lung Carcinoma
Pancreatic Carcinoma
Progesterone Receptor Negative
Rectal Carcinoma
Renal Cell Carcinoma
Soft Tissue Sarcoma
Triple-Negative Breast Carcinoma
TP53 Gene Mutation
Unresectable Solid Neoplasm

OTHER: Laboratory Biomarker Analysis
BIOLOGICAL: Modified Vaccinia Virus Ankara Vaccine Expressing p53
BIOLOGICAL: Pembrolizumab

15002
NCI-2015-00653 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
15002 (OTHER Identifier) (OTHER: City of Hope Medical Center)

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-04-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-03-18
First Submitted that Met QC Criteria 2015-05-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-03-20
First Posted (ACTUAL) 2015-05-04	Results First Posted N/A	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (p53MVA, pembrolizumab) Patients receive pembrolizumab IV over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 SC at least 30 minutes later once in weeks 1, 4, and 7. Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19,	OTHER: Laboratory Biomarker Analysis Correlative studies BIOLOGICAL: Modified Vaccinia Virus Ankara Vaccine Expressing p53 Given SC BIOLOGICAL: Pembrolizumab Given IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (p53MVA, pembrolizumab)

Patients receive pembrolizumab IV over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 SC at least 30 minutes later once in weeks 1, 4, and 7. Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19,

OTHER: Laboratory Biomarker Analysis

Correlative studies

BIOLOGICAL: Modified Vaccinia Virus Ankara Vaccine Expressing p53

Given SC

BIOLOGICAL: Pembrolizumab

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Tolerability of combined modified vaccinia virus Ankara vaccine expressing p53 and pembrolizumab, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.3		Up to week 20

Secondary Outcome Measures	Measure Description	Time Frame
Clinical responses, assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST)	Evaluated using immune-related response criteria (irRECIST, irRC).	Up to week 19
T cell reactivity to p53, assessed by flow cytometry	Immunosuppressive cell types (MDSC, Tregs) and other selected lymphocyte subsets and markers including PD-1, PDL-1 and PDL-2 will be quantified. The Wilcoxon rank-sum test will be used, and are based on residual re-sampling simulations based on historical AUC values (subtracting baseline) and a hypothesized increase in that AUC.	Up to week 19

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Since p53 mutations occur in a wide variety of tumor types, this is a mixed histology study for incurable tumors; subjects with the following solid tumors are eligible for screening: non-small cell lung cancer, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, renal cell carcinoma, melanoma, bladder, soft tissue sarcoma, triple-negative breast cancer, and colorectal carcinoma displaying microsatellite instability and pancreatic cancer
Advanced (unresectable) solid tumors: patients must have failed or been intolerant to at least one line of standard therapy or refuse standard treatment
Performance status: patients must have an Eastern Cooperative Oncology Group (ECOG) =< 2 (Karnofsky >= 60%)
Informed consent: all subjects must have the ability to understand and the willingness to sign an Institutional Review Board (IRB) approved consent form
Absolute neutrophil count: >= 1,500/ul
Platelets >= 100,000/ul
Hemoglobin level: must be greater than 9 g/dL
Renal function: calculated or measured creatinine clearance >= 50 ml/min and/or serum creatinine =< 1.6 mg/dl
Total bilirubin =< 1.5 x institutional upper limit of normal
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times institutional upper normal level (AST and ALT =< 5 times institutional upper normal level, if there is evidence of liver metastasis)
Confirmed p53 involvement: patients with p53 over-expression by immunohistochemistry (>= 10% of cells within the tumor staining positive) or those with a p53 mutation as determined by mutational analysis of tumor tissue will be eligible; patients with prior exposure to p53-based vaccines will be eligible
Agreement to use adequate contraception: women of child-bearing potential must use contraception prior to study entry and for six months after study participation; men that are sexually active whose partners are women of childbearing age must use condoms

Patients may not be receiving any additional investigational agents or radiation therapy
Pregnancy: pregnant women are excluded from this study; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; women who are pregnant or breastfeeding are excluded
Patients with known brain metastasis
Radiotherapy within 4 weeks prior to entering the study
Patients with previous exposure to anti-programmed cell death (PD)-1 or anti-programmed cell death ligand 1 (PDL-1) will not be eligible
History of allergy to egg proteins
Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Concurrent use of systemic corticosteroids (nasal corticosteroids, inhaled steroids, adrenal replacement steroids, and topical steroids are allowed)
History of immunodeficiency or autoimmune disease: patients with a history of immunodeficiency, including organ grafts and human immunodeficiency virus (HIV), will not be eligible
Patients with a history of autoimmune disease will also be excluded, specifically those with any active autoimmune disease or a condition that requires systemic corticosteroids; exceptions to this are subjects with vitiligo and type I diabetes mellitus, who will be permitted to enroll
Patients with a history of severe immune-mediated adverse reactions with ipilimumab: this will be defined as any grade 4 toxicity requiring treatment with corticosteroids (greater than 10 mg/day prednisone or equivalent dose) for greater than 12 weeks
Patients with a history of cardiac disease are excluded; baseline electrocardiography and assessment of serum troponin (I) are included the screening exams; subjects in whom these assays are abnormal (electrocardiogram [EKG] excluding 1st degree bundle branch block, sinus bradycardia, sinus tachycardia or non-specific T wave changes, serum troponin >= grade 2) are ineligible
Non-compliance: if it is the opinion of the investigator that a subject may be unable to comply with the safety monitoring requirements of the study, they will be excluded

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Vincent Chung, City of Hope Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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