NCT06411691 · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer
What this study is about
Phase 1b study evaluating the effectiveness 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.
View original scientific 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.
Interventions
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, arms and/or back. Drug: 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC
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: 240 mg IV
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
Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort
Time frame: 4 months
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.
Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort
Time frame: 3 years
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.
Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort
Time frame: 3 years
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.
Number of participants experiencing study drug-related toxicities
Time frame: 3 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion 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.
Exclusion criteria
- 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.
Where
- Baltimore, Maryland
Collaborators
Agenus Inc., Private Philanthropic Funds, National Cancer Institute (NCI), United States Department of Defense
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Dec 18, 2025 · Source of record for eligibility and locations