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

NCT04117087 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: J1994IRB002109155P01CA247886K08CA248624
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Baseline, 16 weeks

Secondary Outcomes (5)

• Disease Free Survival (DFS)

  4 years

• Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells

  2 years

• Objective Response Rate (ORR) per RECIST 1.1

  4 years

• Progression-free Survival (PFS) for RECIST 1.1

  4 years

• Overall Survival (OS)

  4 years

Study Arms (2)

Treatment Phase

EXPERIMENTAL

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Drug: KRAS peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab

Reinduction Treatment Phase

EXPERIMENTAL

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Drug: KRAS peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab 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

Also known as: OPDIVO

Reinduction Treatment Phase; Treatment Phase

Ipilimumab 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

Also known as: YERVOY®

Reinduction Treatment Phase; Treatment Phase

KRAS peptide vaccine 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

Also known as: Hiltonol® (Poly-ICLC)

Reinduction Treatment Phase; Treatment Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• Huff AL, Haldar SD, Gergis 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.

  PMID: 41667470 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms

Interventions

poly ICLC; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nilofer Azad, MD

  Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 7, 2019
• Study Start: May 28, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)