ACTIVE_NOT_RECRUITING

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected Mismatch Repair Protein (MMR-p) Colorectal and Pancreatic Cancer

Conditions

Colorectal Cancer Pancreatic Cancer KRAS Peptide Vaccine Nivolumab Ipilimumab Anti-PD-1 Anti-CTLA-4 Neoantigen Vaccines Cancer Vaccines Immunotherapy Colon Cancer Pancreatic Ductal Adenocarcinoma (PDAC)Resected MMR-p Colorectal Cancer Resected MMR-p Pancreatic Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Phase 1 study for patients with resected PDAC after neoadjuvant and/ or adjuvant chemotherapy and/or radiation, as well as patients with metastatic colorectal cancer who have exposure to 2 or more lines of chemotherapy, to evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant in combination with nivolumab and ipilimumab.

Official Title

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer

Quick Facts

Study Start:2020-05-28

Study Completion:2025-08-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04117087

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:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Have histologically or cytologically - proven cancer of the pancreas (PDA) or MSS colorectal (CRC) in one of the following categories: * PDAC must have no evidence of disease and last dose of neoadjuvant and/or adjuvant chemotherapy/radiation therapy/or surgery must be \< 6 months from study entry. * Metastatic MSS CRC after exposure to 2 more lines of chemotherapy in the metastatic setting including 5-flurouracil, irinotecan, and oxaliplatin exposure. Patients treated with FOLFOXIRI may enroll after progression or intolerance to that regimen. * For metastatic MSS CRC cohort, must 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 Principal Investigator). * For metastatic MSS CRC patients, must have measurable disease per RECIST 1.1. * Have a single site of locoregional recurrence or distant metastasis noted on imaging \> 12 months after the first dose of the mutant KRAS peptide vaccine with poly-ICLC adjuvant. * Have completed definitive treatment for solitary recurrence per standard-of-care (e.g. surgical resection, radiation, and/or chemotherapy) \<6 months prior to screening for reinduction treatment. * Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping. * Have one of the KRAS mutations included in the vaccine at the time of vaccination expressed in tumor. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * 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. * If expected to require any other form of systemic or localized antineoplastic therapy while on study. * Within 2 weeks prior to first dose of study drug. * Systemic or topical steroids corticosteroids at immunosuppressive doses (\> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. * Any palliative or adjuvant radiation or gamma knife radiosurgery. * Any chemotherapy. * Within 4 weeks prior to first dose of study drug. * Any investigational cytotoxic drug. * Any investigational device. * Has received a live vaccine. * Received any allergen hyposensitization therapy. * Received any growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin. * Any major surgery. * PDAC or metastatic MSS CRC Cohort: Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), etc.). * Hypersensitivity reaction to any monoclonal antibody. * Known history or evidence of brain metastases. * Has active autoimmune disease that has required systemic treatment in the past 2 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 \< 92% 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 a diagnosis of immunodeficiency. * Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded. * 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. * For metastatic MSS CRC and Reinduction Treatment Cohorts, any peritoneal involvement by the tumor. * For metastatic MSS CRC and Reinduction Treatment Cohorts, any radiological or clinical pleural effusions or ascites. * For metastatic MSS CRC and Reinduction Treatment Cohorts, patients on parenteral nutrition. * For metastatic MSS CRC and Reinduction Treatment Cohorts, patients with any single liver metastases greater than 5 cm or greater \> 50% liver involvement. * For metastatic MSS CRC and Reinduction Treatment Cohorts, history of malignant bowel obstruction.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* Have histologically or cytologically - proven cancer of the pancreas (PDA) or MSS colorectal (CRC) in one of the following categories:
* PDAC must have no evidence of disease and last dose of neoadjuvant and/or adjuvant chemotherapy/radiation therapy/or surgery must be \< 6 months from study entry.
* Metastatic MSS CRC after exposure to 2 more lines of chemotherapy in the metastatic setting including 5-flurouracil, irinotecan, and oxaliplatin exposure. Patients treated with FOLFOXIRI may enroll after progression or intolerance to that regimen.
* For metastatic MSS CRC cohort, must 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 Principal Investigator).
* For metastatic MSS CRC patients, must have measurable disease per RECIST 1.1.
* Have a single site of locoregional recurrence or distant metastasis noted on imaging \> 12 months after the first dose of the mutant KRAS peptide vaccine with poly-ICLC adjuvant.
* Have completed definitive treatment for solitary recurrence per standard-of-care (e.g. surgical resection, radiation, and/or chemotherapy) \<6 months prior to screening for reinduction treatment.
* Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
* Have one of the KRAS mutations included in the vaccine at the time of vaccination expressed in tumor.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* 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.
* If expected to require any other form of systemic or localized antineoplastic therapy while on study.
* Within 2 weeks prior to first dose of study drug.
* Systemic or topical steroids corticosteroids at immunosuppressive doses (\> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Any palliative or adjuvant radiation or gamma knife radiosurgery.
* Any chemotherapy.
* Within 4 weeks prior to first dose of study drug.
* Any investigational cytotoxic drug.
* Any investigational device.
* Has received a live vaccine.
* Received any allergen hyposensitization therapy.
* Received any growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin.
* Any major surgery.
* PDAC or metastatic MSS CRC Cohort: Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), etc.).
* Hypersensitivity reaction to any monoclonal antibody.
* Known history or evidence of brain metastases.
* Has active autoimmune disease that has required systemic treatment in the past 2 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 \< 92% 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 a diagnosis of immunodeficiency.
* Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
* 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.
* For metastatic MSS CRC and Reinduction Treatment Cohorts, any peritoneal involvement by the tumor.
* For metastatic MSS CRC and Reinduction Treatment Cohorts, any radiological or clinical pleural effusions or ascites.
* For metastatic MSS CRC and Reinduction Treatment Cohorts, patients on parenteral nutrition.
* For metastatic MSS CRC and Reinduction Treatment Cohorts, patients with any single liver metastases greater than 5 cm or greater \> 50% liver involvement.
* For metastatic MSS CRC and Reinduction Treatment Cohorts, history of malignant bowel obstruction.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Nilofer Azad, MD

PRINCIPAL_INVESTIGATOR

Johns Hopkins Medical Institution

Study Locations (Sites)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Nilofer Azad, MD, PRINCIPAL_INVESTIGATOR, 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 Registration Dates

Study Start Date2020-05-28

Study Completion Date2025-08-08

Study Record Updates

Study Start Date2020-05-28

Study Completion Date2025-08-08

Terms related to this study

Keywords Provided by Researchers

KRAS Peptide Vaccine
Nivolumab
Ipilimumab
Anti-PD-1
Anti-CTLA-4
Neoantigen Vaccines
Cancer Vaccines
Immunotherapy
Colon Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
Resected MMR-p Colorectal Cancer
Resected MMR-p Pancreatic Cancer

Additional Relevant MeSH Terms

Colorectal Cancer
Pancreatic Cancer