Colorectal CancerPhase 1NCT04117087

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

A Phase 1 study testing KRAS peptide vaccine, Nivolumab and Ipilimumab in people with Colorectal Cancer and Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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… 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 peptide vaccine, Nivolumab and Ipilimumab
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 1 siteUnited States
Study dates: 28 May 2020to 1 Jun 2027
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

PDAC or metastatic MSS CRC Cohort:
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.

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Reinduction Treatment Cohort:
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.
Both Cohorts:
Age ≥18 years.
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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231

Other trials in United States

About this study

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

Conditions: Colorectal Cancer, Pancreatic Cancer
Being tested: KRAS peptide vaccine, Nivolumab, Ipilimumab
Keywords: 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
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 peptide vaccineDrug
Also called Hiltonol® (Poly-ICLC)
1. KRAS peptide vaccine will be administered on cycle 1 (days 1, 8, 15) and R-Cycle 2 Day 1 (R-C2D1). Boost vaccinations with will be administered every 28 days at Reinduction cycle 5, 7, 9, 13. Extended vaccinations will be administered on Reinduction cycles 15 to 18, 19 and beyond (180 days ± 30 days for a total of 5 years on study.
2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC
NivolumabDrug
Also called OPDIVO
1. Nivolumab will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of each 21 day cycle. Boost Phase will be administered every 28 days on cycles 5 thru 14.
2. Drug: 3mg/kg IV, 480 mg IV
IpilimumabDrug
Also called YERVOY®
1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of Cycles 1 and 3 of the study.
2. Drug: 1mg/kg IV

Study groups in NCT04117087
Study group	Role	What they receive
Treatment Phase	Experimental	KRAS Vaccine Peptide, Nivolumab and Ipilimumab Receives: Drug: KRAS peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab
Reinduction Treatment Phase	Experimental	KRAS Vaccine Peptide, Nivolumab and Ipilimumab Receives: Drug: KRAS peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

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: 2 years
Fold change in interferon-producing mutant-KRAS-specific cytotoxic (CD8) and helper (CD4) T cells at 16 weeks
Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells after vaccination at 16 weeks compare to pre-vaccination baseline.
Measured: Baseline, 16 weeks

Secondary outcomes (5)

Disease Free Survival (DFS)
DFS is defined as the number of months from cycle 1, day 1 of vaccination until the first documented disease recurrence or death due to any cause in patients with resected PDAC. Will be censored at the date of the last progressive disease evaluation if no event observed.
Measured: 4 years
Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells
Percent change of IFN-γ-producing mutant-KRAS-specific CD8 and CD4 T cells at any time after vaccination.
Measured: 2 years
Objective Response Rate (ORR) per RECIST 1.1
ORR is defined as the number of patients with metastatic microsatellite stable (MSS) CRC who are administered at least one dose of KRAS achieving a complete response (CR) 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 percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20 percent increase in sum of diameters of target lesions, stable disease (SD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions.
Measured: 4 years
Progression-free Survival (PFS) for RECIST 1.1
PFS is defined as the numbers of months from the date of the first vaccine dose to the date of disease progression or death due to any cause, which ever occurs first, for Metastatic Colorectal Cancer (mCRC) patients. Censored at the date of last scan for subjects without documentation of disease progression (PD) at the time of analysis 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 percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20 percent increase in sum of diameters of target lesions, Stable Disease (SD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions.
Measured: 4 years
Overall Survival (OS)
OS will be measured as the number of months from the date of first vaccine dose until death or end of follow up. OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan Meier Curve
Measured: 4 years

Timeline

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

28 May 20201 Jun 2027

First posted7 Oct 2019
Study start28 May 2020
Primary completion1 Jun 2027 (estimated)
Study completion1 Jun 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04117087
Sponsor's protocol ID: J1994
Other IDs: IRB00210915, 5P01CA247886, K08CA248624
Status last verified: Jul 2026
First submitted: 3 Oct 2019
Last updated: 27 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Huff AL, Haldar SD, Girgis AA, Wang HH, Danilova L, Heumann T, Berg M, Wang Y, Andaloori L, Hernandez A, Longway G, Barrett B, Zhu Z, Davis-Marcisak E, Thoburn C, Leatherman J, Mitchell S, Lee JW, Shu DH, Konig MF, Mog BJ, Montagne J, Coyne EM, Bever K, Baretti M, Yarchoan M, Anders RA, Kagohara LT, Laheru D, Thomas AM, Durham J, Nauroth JM, Lu J, Wang H, Fertig EJ, Ho WJ, Azad NS, Jaffee EM, Zaidi N. Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial. Nat Commun. 2026 Feb 10;17(1):1538. doi: 10.1038/s41467-026-68324-4.
PubMed 41667470

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer
ClinicalTrials.gov ID: NCT04117087
Acronym / sponsor ID: J1994
Conditions: Colorectal Cancer, Pancreatic Cancer
Keywords: KRAS Peptide Vaccine, Nivolumab, Ipilimumab, Anti-PD-1, Anti-CTLA-4, Neoantigen Vaccines, Cancer Vaccines, Immunotherapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 27 participants (actual)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
Collaborators: Bristol-Myers Squibb, National Cancer Institute (NCI), National Institutes of Health (NIH)
Study start: 28 May 2020 (actual)
Primary completion: 1 Jun 2027 (estimated)
Study completion: 1 Jun 2027 (estimated)
First posted: 7 Oct 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment Phase	Experimental	Drug: KRAS peptide vaccine, Drug: Nivolumab, Drug: IpilimumabKRAS Vaccine Peptide, Nivolumab and Ipilimumab
Reinduction Treatment Phase	Experimental	Drug: KRAS peptide vaccine, Drug: Nivolumab, Drug: IpilimumabKRAS Vaccine Peptide, Nivolumab and Ipilimumab

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Have histologically or cytologically - proven cancer of the pancreas (PDA) or MSS colorectal (CRC) in one of the following categories:
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.

Key exclusion criteria (32 listed)

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.
Within 4 weeks prior to first dose of study drug.
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KRAS peptide vaccineAlso: Hiltonol® (Poly-ICLC)1. KRAS peptide vaccine will be administered on cycle 1 (days 1, 8, 15) and R-Cycle 2 Day 1 (R-C2D1). Boost vaccinations with will be administered every 28 days at Reinduction cycle 5, 7, 9, 13. Extended vaccinations will be administered on Reinduction cycles 15 to 18, 19 and beyond (180 days ± 30 days for a total of 5 years on study. 2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC	Drug	Reinduction Treatment Phase, Treatment Phase
NivolumabAlso: OPDIVO1. Nivolumab will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of each 21 day cycle. Boost Phase will be administered every 28 days on cycles 5 thru 14. 2. Drug: 3mg/kg IV, 480 mg IV	Drug	Reinduction Treatment Phase, Treatment Phase
IpilimumabAlso: YERVOY®1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of Cycles 1 and 3 of the study. 2. Drug: 1mg/kg IV	Drug	Reinduction Treatment Phase, Treatment Phase

Primary outcome

Number of participants experiencing study drug-related toxicities
Time frame: 2 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Fold change in interferon-producing mutant-KRAS-specific cytotoxic (CD8) and helper (CD4) T cells at 16 weeks
Time frame: Baseline, 16 weeks
Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells after vaccination at 16 weeks compare to pre-vaccination baseline.

5 secondary outcomes

Disease Free Survival (DFS)
Time frame: 4 years
Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells
Time frame: 2 years
Objective Response Rate (ORR) per RECIST 1.1
Time frame: 4 years
Progression-free Survival (PFS) for RECIST 1.1
Time frame: 4 years
Overall Survival (OS)
Time frame: 4 years

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
Derived from this study: PubMed 41667470Huff AL, Haldar SD, Girgis AA, Wang HH, Danilova L, Heumann T, Berg M, Wang Y, Andaloori L, Hernandez A, Longway G, Barrett B, Zhu Z, Davis-Marcisak E, Thoburn C, Leatherman J, Mitchell S, Lee JW, Shu DH, Konig MF, Mog BJ, Montagne J, Coyne EM, Bever K, Baretti M, Yarchoan M, Anders RA, Kagohara LT, Laheru D, Thomas AM, Durham J, Nauroth JM, Lu J, Wang H, Fertig EJ, Ho WJ, Azad NS, Jaffee EM, Zaidi N. Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial. Nat Commun. 2026 Feb 10;17(1):1538. doi: 10.1038/s41467-026-68324-4.
Individual participant dataSharing planned: No

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RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nilofer Azad, MD principal investigator

Johns Hopkins Medical Institution

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 19 inclusion and 32 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: under way, not looking for participants, as of the sponsor's last update on 27 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants experiencing study drug-related toxicities (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04117087, which also lists 1 linked publication.

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 27 Jul 2026.