Phase 1 study for patients with resected PDAC after neoadjuvant and/ or adjuvant chemotherapy and/or radiation, as well as patients with metastatic MSS CRC who have progressed on 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.
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| KRAS peptide vaccine | Hiltonol® (Poly-ICLC) | KRAS peptide vaccine, Nivolumab, and Ipilimumab |
| Nivolumab | OPDIVO | KRAS peptide vaccine, Nivolumab, and Ipilimumab |
| Ipilimumab | YERVOY® | KRAS peptide vaccine, Nivolumab, and Ipilimumab |
| Name | Type | Description | Interventions |
|---|---|---|---|
| KRAS peptide vaccine, Nivolumab, and Ipilimumab | Experimental |
|
Inclusion Criteria:
- Age ≥18 years.
- 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 progression on 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.
- Have sufficient archival tumor tissue for next-generation sequencing (NGS) and
immune-phenotyping.
- Have one of the six KRAS mutations (KRASG12C, KRASG12V, KRASG12D, KRASG12A, KRASG13D
or KRASG12R) 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.
- Any systemic or topical corticosteroids at immunosuppressive agents.
- 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.
- 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 cohort, any peritoneal involvement by the tumor.
- For metastatic MSS CRC cohort, any radiological or clinical pleural effusions or
ascites.
- For metastatic MSS CRC cohort, patients on parenteral nutrition.
- For metastatic CRC cohort, patients with any single liver metastases greater than 5 cm
or greater > 50% liver involvement.
- For metastatic MSS CRC cohort, history of malignant bowel obstruction.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Number of participants experiencing study drug-related toxicities |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0 |
| Measure: | Disease Free Survival (DFS) |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | DFS is defined as the number of months from cycle 1, day 1 of vaccination until the first documented disease recurrence or death due to any cause in patients with resected PDAC. Will be censored at the date of the last progressive disease evaluation if no event observed. |
| Measure: | Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells |
| Time Frame: | Baseline, 4 years |
| Safety Issue: | |
| Description: | Percent change of IFN-γ-producing mutant-KRAS-specific CD8 and CD4 T cells at any time after vaccination. |
| Measure: | Objective Response Rate (ORR) per RECIST 1.1 |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | ORR is defined as the number of patients with metastatic MSS CRC who are administered at least one dose of KRAS achieving a complete response (CR) partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30 percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20 percent increase in sum of diameters of target lesions, stable disease (SD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions. |
| Measure: | Objective Response Rate (ORR) per iRECIST |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | ORR is defined as the number of patients with metastatic MSS CRC who are administered at least one dose of KRAS achieving a complete response (iCR) partial response (iPR) based on the Response Evaluation Criteria in Solid Tumors (iRECIST) at any time during the study. iCR = disappearance of all target lesions, iPR is =>30 percent decrease in sum of diameters of target lesions, progressive disease (iPD) is >20 percent increase in sum of diameters of target lesions, stable disease (iSD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions. |
| Measure: | Progression-free Survival (PFS) for RECIST 1.1 |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | PFS is defined as the numbers of months from the date of the first vaccine dose to the date of disease progression or death due to any cause, which ever occurs first, for mCRC patients. Censored at the date of last scan for subjects without documentation of disease progression (PD) at the time of analysis or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30 percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20 percent increase in sum of diameters of target lesions, Stable Disease (SD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions. |
| Measure: | Progression-free Survival (PFS) for iRECIST |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | PFS per iRECIST is defined as the numbers of months from the date of the first vaccine dose to the date of disease progression or death due to any cause, which ever occurs first, for mCRC patients. Censored at the date of last scan for subjects without documentation of disease progression (iPD) at the time of analysis or relapse from complete response [iCR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per iRECIST (iPFS) criteria, iCR = disappearance of all target lesions, Partial Response (iPR) is =>30 percent decrease in sum of diameters of target lesions, Progressive Disease (iPD) is >20 percent increase in sum of diameters of target lesions, Stable Disease (iSD) is <30 percent decrease or <20 percent increase in sum of diameters of target lesions. |
| Measure: | Overall Survival (OS) |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | OS will be measured as the number of months from the date of first vaccine dose until death or end of follow up. OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan Meier Curve |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
August 20, 2021
