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

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

NCT ID: NCT06411691

Condition: Colorectal Cancer
Pancreatic Cancer

Conditions: Official terms:
Colorectal Neoplasms
Pancreatic Neoplasms
Poly I-C
Carboxymethylcellulose Sodium
Poly ICLC

Conditions: 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

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: KRAS Vaccine with Poly-ICLC adjuvant
Description: 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
Arm group label: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab

Other name: Hiltonol® (Poly-ICLC)

Intervention type: Drug
Intervention name: Balstilimab
Description: 75 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: 75 mg IV
Arm group label: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab

Other name: AGEN2034

Intervention type: Drug
Intervention name: Botensilimab
Description: 240 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 1 in the Boost Phase. Drug: 240 mg IV
Arm group label: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab

Other name: AGEN1181

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 FOLFIRINOX/FOLFOXIRI (FFX).

Criteria for eligibility:
Criteria:
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. - Have received 4-6 months of FOLFIRINOX for the treatment of metastatic or unresectable PDAC or CRC. - 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 within the past 5 year. - 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Sidney Kimmel Comprehensive Cancer Center

Address:
City: Baltimore
Zip: 21231
Country: United States

Status: Recruiting

Contact:
Last name: Colleen Apostol, RN

Phone: 410-614-3644
Email: GIClinicalTrials@jhmi.edu

Contact backup:
Last name: Joann Santmyer, RN

Phone: 410-614-3644
Email: GIClinicalTrials@jhmi.edu

Start date: November 4, 2024

Completion date: November 2027

Lead sponsor:
Agency: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class: Other

Collaborator:
Agency: Agenus Inc.
Agency class: Industry

Collaborator:
Agency: Private Philanthropic Funds
Agency class: Other

Collaborator:
Agency: National Institutes of Health (NIH)
Agency class: NIH

Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06411691