Vaccine treatment for advanced colorectal and pancreatic cancer

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

This study is testing a new vaccine combined with two other treatments to see if it can help people with advanced colorectal and pancreatic cancer who haven't responded to their first treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Balstilimab, Botensilimab
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06411691 on ClinicalTrials.gov

What this trial studies

This Phase 1b study evaluates the effectiveness and immune response of a synthetic long peptide mutant KRAS vaccine combined with Balstilimab and Botensilimab in patients with unresectable or metastatic mismatch repair-proficient colorectal cancer and pancreatic ductal adenocarcinoma. Participants must have measurable disease following first-line chemotherapy and will undergo tumor biopsies for analysis. The study aims to assess the safety and efficacy of this novel combination therapy in a targeted patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed stage IV colorectal or pancreatic cancer who have specific KRAS mutations and measurable disease after first-line chemotherapy.

Not a fit: Patients who have not received prior chemotherapy or those with resectable tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced colorectal and pancreatic cancers that are currently difficult to treat.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

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.

Where this trial is running

Baltimore, Maryland

• Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Nilofer Azad, MD — SKCCC Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostol, RN

Conditions Colorectal Cancer; Pancreatic Cancer; mKRAS peptide vaccines; Anti-PD-1; PD-L1; Balstilimab; Botensilimab; Cancer Vaccines