Colorectal Cancer, Pancreatic Cancer
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
Brief 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 chemotherapy.
Interventions
DRUGKRAS 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
DRUGBalstilimab
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
DRUGBotensilimab
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
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agenus Inc.
Private Philanthropic Funds
National Cancer Institute (NCI)
United States Department of Defense
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort | 4 months | PFS is defined as the number of mPDAC patients free of progression at 4 months since the initiation of therapy - disease progression (progressive disease \[PD\] 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 =\>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20percent increase in sum of diameters of target lesions, Stable Disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions. |
| Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort | 3 years | ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or 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 =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions. |
| Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort | 3 years | ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or 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 =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions. |
| Number of participants experiencing study drug-related toxicities | 3 years | Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) per RECIST 1.1 | 3 years | ORR is defined as the number of mPDAC patients who are administered at least 1 dose of SLP mKRASvax and balstilimab +/- botensilimab achieving a complete response (CR) or 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% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. |
| Disease Control Rate (DCR) | 2 months | DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 2 months post first vaccination. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
| Progression-free Survival (PFS) per RECIST 1.1 | 3 years | PFS is defined as the time from cycle 1, day 1 of KRAS vaccine and balstilimab and botensilimab until first documented local disease progression (progressive disease \[PD\] 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% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
Countries
United States
Contacts
CONTACTColleen Apostol, RN
PRINCIPAL_INVESTIGATORNilofer Azad, MD
SKCCC Johns Hopkins Medical Institution
Outcome results
None listed