Vaccine combined with immune therapy for colorectal and pancreatic cancer patients

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer

This study is testing a new vaccine combined with immune therapy to see if it can help patients with certain types of colorectal and pancreatic cancer fight their cancer better after treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, nivolumab, ipilimumab
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT04117087 on ClinicalTrials.gov

What this trial studies

This Phase 1 study evaluates the safety and immune response of a pooled mutant KRAS-targeted long peptide vaccine in combination with nivolumab and ipilimumab for patients with resected pancreatic ductal adenocarcinoma (PDAC) and metastatic colorectal cancer. Patients with PDAC must have no evidence of disease after recent chemotherapy or surgery, while those with colorectal cancer must have undergone at least two lines of chemotherapy. The study aims to assess the effectiveness of this combination therapy in enhancing the immune response against cancer cells.

Who should consider this trial

Good fit: Ideal candidates include patients with resected PDAC within six months of treatment or metastatic colorectal cancer who have received at least two lines of chemotherapy.

Not a fit: Patients with early-stage colorectal or pancreatic cancer who have not undergone prior chemotherapy or surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with colorectal and pancreatic cancers by enhancing their immune response.

How similar studies have performed: Other studies have shown promise in using immune therapies combined with vaccines for cancer treatment, indicating potential for success in this approach.

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.

Where this trial is running

Baltimore, Maryland

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

Study contacts

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

Conditions Colorectal Cancer; Pancreatic Cancer; KRAS Peptide Vaccine; Nivolumab; Ipilimumab; Anti-PD-1; Anti-CTLA-4; Neoantigen Vaccines