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Colorectal CancerPhase 1NCT06411691

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

A Phase 1 study testing KRAS Vaccine with Poly-ICLC adjuvant, Balstilimab and Botensilimab in people with Colorectal Cancer and Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer, Pancreatic Cancer
What is being tested?
KRAS Vaccine with Poly-ICLC adjuvant, Balstilimab and Botensilimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
4 Nov 2024to 1 Nov 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Colleen Apostol, RN contact

410-614-3644

GIClinicalTrials@jhmi.edu

United States1 site, 1 recruiting
  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

    Colleen Apostol, RN, 410-614-3644, GIClinicalTrials@jhmi.edu

    Recruiting

Other trials in United States

About this study

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

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.

Being tested
KRAS Vaccine with Poly-ICLC adjuvant, Balstilimab, Botensilimab
Keywords
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
Medical subject headings
Colorectal Neoplasms, Pancreatic Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KRAS Vaccine with Poly-ICLC adjuvantDrug

    Also called Hiltonol® (Poly-ICLC)

    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

  • BalstilimabDrug

    Also called AGEN2034

    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

  • BotensilimabDrug

    Also called AGEN1181

    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

Study groups in NCT06411691
Study groupRoleWhat they receive
SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and BalstilimabExperimentalNot described
Receives: Drug: KRAS Vaccine with Poly-ICLC adjuvant; Drug: Balstilimab; Drug: Botensilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 4 months

  2. 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.

    Measured: 3 years

  3. 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.

    Measured: 3 years

  4. 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

    Measured: 3 years

Secondary outcomes (5)
  1. 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.

    Measured: 3 years

  2. 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.

    Measured: 2 months

  3. 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.

    Measured: 6 months

  4. 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.

    Measured: 12 months

  5. 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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2024
  2. Study start4 Nov 2024
  3. Primary completion1 Nov 2029 (estimated)
  4. Study completion1 Nov 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06411691
Sponsor's protocol ID
J2456
Other IDs
IRB00427416, 1R01CA296410-01, HT94252410948
Status last verified
Jul 2026
First submitted
8 May 2024
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KRAS Vaccine with Poly-ICLC adjuvant, Balstilimab and Botensilimab in people with Colorectal Cancer and Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Colleen Apostol, RN (410-614-3644, GIClinicalTrials@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort (time frame: 4 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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