Recruiting
Phase 1

KRAS-Targeted Vaccine, Balstilimab, Botensilimab

Sponsor:

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Code:

NCT06411691

Conditions

Colorectal Cancer

Pancreatic Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

KRAS Vaccine with Poly-ICLC adjuvant

Balstilimab

Botensilimab

Study Details

Brief 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 adenocarcinoma (PDAC) patients with measurable disease following first-line chemotherapy.

Conditions

Colorectal Cancer

Pancreatic Cancer

Study ID

NCT06411691

Start date

Nov 4, 2024

Status verified date

Jul, 2026

Completion date

Nov 1, 2030

Anticipated

Primary completion date

Nov 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

54 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

Interventions

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

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

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 measure

  • Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort [ Time Frame: 4 months ]
  • Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort [ Time Frame: 3 years ]
  • Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort [ Time Frame: 3 years ]
  • Number of participants experiencing study drug-related toxicities [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Colleen Apostol, RN

410-614-3644GIClinicalTrials@jhmi.edu

Locations

Sidney Kimmel Comprehensive Cancer Center

Recruiting

Baltimore, Maryland, United States, 21231

Contacts

Colleen Apostol, RN

410-614-3644GIClinicalTrials@jhmi.edu

More Information

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last update posted

Jul 31, 2026

Last verified

Jul, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on 2026-07-31.