Clinical trial NCT06411691: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Pancreatic Cancer
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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Agenus Inc.
name: Private Philanthropic Funds
name: National Cancer Institute (NCI)
name: United States Department of Defense
First posted: 2024-05-13
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort
timeFrame: 4 months
measure: Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort
timeFrame: 3 years
measure: Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort
timeFrame: 3 years
measure: Number of participants experiencing study drug-related toxicities
timeFrame: 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR) per RECIST 1.1
timeFrame: 3 years
measure: Disease Control Rate (DCR)
timeFrame: 2 months
measure: Disease Control Rate (DCR)
timeFrame: 6 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Progression-free Survival (PFS) per RECIST 1.1
timeFrame: 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: SKCCC Johns Hopkins Medical Institution
name: Nilofer Azad, MD
role: PRINCIPAL_INVESTIGATOR
References: