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

Official title

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Adenocarcinoma

Overview

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.

Interventions

• Drug 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
• Drug 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
• Drug 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 measures

• 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]

Secondary outcome measures (5)

• Objective Response Rate (ORR) per RECIST 1.1 [Time frame: 3 years]
• Disease Control Rate (DCR) [Time frame: 2 months]
• Disease Control Rate (DCR) [Time frame: 6 months]
• Disease Control Rate (DCR) [Time frame: 12 months]
• Progression-free Survival (PFS) per RECIST 1.1 [Time frame: 3 years]

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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Sidney Kimmel Comprehensive Cancer Center — Baltimore

Identifiers

NCT: NCT06411691 · J2456 · IRB00427416 · 1R01CA296410-01 · HT94252410948

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗