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

Study Overview

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

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.

N/A

Colorectal Cancer
Pancreatic Cancer

DRUG: KRAS Vaccine with Poly-ICLC adjuvant
DRUG: Balstilimab
DRUG: Botensilimab

J2456
IRB00427416 (OTHER Identifier) (OTHER: Johns Hopkins Medicine IRB)
1R01CA296410-01 (U.S. NIH Grant/Contract)
HT94252410948 (OTHER_GRANT Identifier) (OTHER_GRANT: Department of Defense)

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 2024-05-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-03
First Submitted that Met QC Criteria 2024-05-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-06
First Posted (ACTUAL) 2024-05-13	Results First Posted N/A	Last Verified 2025-04

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: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab	DRUG: KRAS Vaccine with Poly-ICLC adjuvant SLP mKRASvax with Poly-ICLC adjuvant will be administered on days 1, 8, 15 and 22 in Cycle 1 (Prime Phase) and on day 1 in cycle 4 and every other cycle and beyond (Boost Phase). Up to 5 subcutaneous injections will be administered in the upper thighs, ar DRUG: Balstilimab 240 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on day 1 and day 15 during Cycle 1 in Prime Phase and on day 1 and day 15 of every cycle in the Boost Phase beginning on Cycle 2 (for a maximum of 2 years from initial vaccination). DRUG: Botensilimab 75 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on Cycle 1 day 1 in Prime Phase and on Cycle 2 day 15 in the Boost Phase. Drug: 75 mg IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab

DRUG: KRAS Vaccine with Poly-ICLC adjuvant

SLP mKRASvax with Poly-ICLC adjuvant will be administered on days 1, 8, 15 and 22 in Cycle 1 (Prime Phase) and on day 1 in cycle 4 and every other cycle and beyond (Boost Phase). Up to 5 subcutaneous injections will be administered in the upper thighs, ar

DRUG: Balstilimab

240 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on day 1 and day 15 during Cycle 1 in Prime Phase and on day 1 and day 15 of every cycle in the Boost Phase beginning on Cycle 2 (for a maximum of 2 years from initial vaccination).

DRUG: Botensilimab

75 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on Cycle 1 day 1 in Prime Phase and on Cycle 2 day 15 in the Boost Phase. Drug: 75 mg IV

Primary Outcome Measures	Measure Description	Time Frame
Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort	PFS is defined as the number of mPDAC patients free of progression at 4 months since the initiation of therapy - 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 =>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20percent increase in sum of diameters of target lesions, Stable Disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.	4 months
Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort	ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax 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 =>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20percent increase in sum of diameters of target lesions, stable disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.	3 years
Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort	ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax 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 =>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20percent increase in sum of diameters of target lesions, stable disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.	3 years
Number of participants experiencing study drug-related toxicities	Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0	3 years

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR) per RECIST 1.1	ORR is defined as the number of mPDAC patients who are administered at least 1 dose of SLP mKRASvax and balstilimab +/- botensilimab 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. Estimation based on the Kaplan-Meier curve.	3 years
Disease Control Rate (DCR)	DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax 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)	DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax 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)	DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax 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	PFS is defined as the time from cycle 1, day 1 of KRAS vaccine and balstilimab and botensilimab until first documented local 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.	3 years

Contacts and Locations

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

Study Contact

Name: Colleen Apostol, RN

Phone Number: 410-614-3644

Email: GIClinicalTrials@jhmi.edu

Study Contact Backup

Name: Joann Santmyer, RN

Phone Number: 410-614-3644

Email: GIClinicalTrials@jhmi.edu

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:

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.

Collaborators and Investigators

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

Agenus Inc.
Private Philanthropic Funds
National Cancer Institute (NCI)
United States Department of Defense

Investigators

PRINCIPAL_INVESTIGATOR: Nilofer Azad, MD, SKCCC Johns Hopkins Medical Institution

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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Clinical Trial Record