RECRUITING

KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer

Conditions

Colorectal Cancer Pancreatic Cancer mKRAS peptide vaccines Anti-PD-1 (anti-check point inhibitor)PD-L1 (check point inhibitor)Balstilimab Botensilimab Cancer Vaccines SLP mKRASvax (peptide vaccine + Poly-ICLC (Hiltonol))Immunotherapy Colon Cancer Metastatic colon cancer Pancreatic Ductal Adenocarcinoma (PDAC)Metastatic pancreatic cancer Hiltonol

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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 1b study evaluating the efficacy and immune response to a synthetic long peptide mutant KRAS vaccine (SPL mKRASvax) combined with Balstilimab and Botensilimab for unresectable or metastatic mismatch repair-proficient (MMR-p) colorectal cancer (mCRC) or unresectable or metastatic MMR-p pancreatic ductal adenocarcinoma (PDAC) patients with measurable disease following first-line chemotherapy.

Official Title

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Adenocarcinoma

Quick Facts

Study Start:2024-11-04

Study Completion:2027-11-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06411691

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
* 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 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. * Cohort A: Have received 4-6 months of FOLFIRINOX or gemcitabine+nab-paclitaxel for the 1st line treatment of metastatic unresectable PDAC. * Cohort B: Have received 4-6 months of 1st line SOC chemotherapy per NCCN guidelines (FOLFIRINOX, FOLFOX, FOLFIRI +/- targeted therapy with VEGFi or EGFRi) of metastatic CRC. * Cohort C: Have received no more than 3 lines of systemic chemotherapy, including prior KRAS inhibitor. * Eastern Cooperative Oncology Group (ECOG) performance status 0. * Life expectancy of greater than 3 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.	* Is a candidate for definitive surgical resection. * 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 in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, DCIS, a low-grade prostate cancer, or a cancer not expected to impact life expectancy and not requiring therapy. * 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. * History of malignant small bowel obstruction. * On parenteral nutrition. * Known or suspected hypersensitivity to Hiltonol.

Inclusion Criteria

Exclusion 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 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.
* Cohort A: Have received 4-6 months of FOLFIRINOX or gemcitabine+nab-paclitaxel for the 1st line treatment of metastatic unresectable PDAC.
* Cohort B: Have received 4-6 months of 1st line SOC chemotherapy per NCCN guidelines (FOLFIRINOX, FOLFOX, FOLFIRI +/- targeted therapy with VEGFi or EGFRi) of metastatic CRC.
* Cohort C: Have received no more than 3 lines of systemic chemotherapy, including prior KRAS inhibitor.
* Eastern Cooperative Oncology Group (ECOG) performance status 0.
* Life expectancy of greater than 3 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.

* Is a candidate for definitive surgical resection.
* 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 in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, DCIS, a low-grade prostate cancer, or a cancer not expected to impact life expectancy and not requiring therapy.
* 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.
* History of malignant small bowel obstruction.
* On parenteral nutrition.
* Known or suspected hypersensitivity to Hiltonol.

Contacts and Locations

Study Contact

Colleen Apostol, RN

CONTACT

410-614-3644

GIClinicalTrials@jhmi.edu

Joann Santmyer, RN

CONTACT

410-614-3644

GIClinicalTrials@jhmi.edu

Principal Investigator

Nilofer Azad, MD

PRINCIPAL_INVESTIGATOR

SKCCC 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, SKCCC 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 Date2024-11-04

Study Completion Date2027-11-01

Study Record Updates

Study Start Date2024-11-04

Study Completion Date2027-11-01

Terms related to this study

Keywords Provided by Researchers

mKRAS peptide vaccines
Anti-PD-1 (anti-check point inhibitor)
PD-L1 (check point inhibitor)
Balstilimab
Botensilimab
Cancer Vaccines
SLP mKRASvax (peptide vaccine + Poly-ICLC (Hiltonol))
Immunotherapy
Colon Cancer
Metastatic colon cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
Metastatic pancreatic cancer
Hiltonol

Additional Relevant MeSH Terms

Colorectal Cancer
Pancreatic Cancer