kras-targeted vaccine combined with balstilimab and botensilimab for patients with stage iv mmr-p colorectal cancer and pancreatic ductal cancer

Conditions: Colorectal Cancer; Pancreatic Cancer

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.

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