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

NCT ID: NCT04117087

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-28
• Study Completion Date: 2027-06-01

Brief 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 vaccine) with poly-ICLC adjuvant in combination with nivolumab and ipilimumab.

Conditions

Colorectal Cancer; Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Phase

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Group Type: EXPERIMENTAL

KRAS peptide vaccine

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

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

Ipilimumab

Intervention Type: DRUG

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

Reinduction Treatment Phase

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Group Type: EXPERIMENTAL

KRAS peptide vaccine

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

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

Ipilimumab

Intervention Type: DRUG

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

Interventions

KRAS peptide vaccine

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

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Ipilimumab

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

Intervention Type: DRUG

Other Intervention Names

Hiltonol® (Poly-ICLC); OPDIVO; YERVOY®

Eligibility Criteria

Inclusion Criteria

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.

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.

Exclusion Criteria

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilofer Azad, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Medical Institution

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00210915

Identifier Type: OTHER

Identifier Source: secondary_id

5P01CA247886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

K08CA248624

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J1994

Identifier Type: -

Identifier Source: org_study_id