PEMBROLIZUMAB for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"-Participant is willing and able to provide written informed consent for participation in the study."}
• {"criterion_text":"-The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of IRCCS IRST and must fulfill all the acceptance criteria prescribed by the GMP procedures"}
• {"criterion_text":"-Recovery (grade 1 or less by CTCAE 5.0) from all the adverse events related to previous surgery"}
• {"criterion_text":"-A female participant is eligible to participate if she is not pregnant and not breastfeeding. Female patients of childbearing potential (WOCBP, pre-menopausal women, from menarche to menopause, capable of becoming pregnant) and all male patients with a partner of childbearing potential must accept and be compliant with a highly effective contraceptive method"}
• {"criterion_text":"-Histologically confirmed pMMR or MSS mCRC"}
• {"criterion_text":"-Male or female, aged ≥ 18 years"}
• {"criterion_text":"-Life expectancy greater than 12 weeks"}
• {"criterion_text":"-ECOG performance status <2"}
• {"criterion_text":"-Patient suitable for the collection of biological material from leukapheresis: negative serological tests (HIV, HBV, HCV, Treponema pallidum); normal cardiological parameters (12-lead ECG and echocardiogram); evaluation by transfusionist to exclude possible contraindications to leukapheresis; recovered (grade 1 or less by CTCAE 5.0) from all the adverse events related to previous treatments"}
• {"criterion_text":"-Patients must have measurable disease by RECIST v 1.1 criteria on CT (or MRI) scan of the chest, abdomen and pelvis. See section 9.2 and Appendix D for the evaluation of measurable disease."}
• {"criterion_text":"-Prior treatment with at least 2 chemotherapy regimens, including (if not contraindicated) fluoropyrimidines, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or anti-EGFR monoclonal antibody for RAS wild-type tumors"}
• {"criterion_text":"-Patients must have normal organ and marrow function as defined below: -\tleukocytes\t >3,000/μL -\tabsolute neutrophil count \t>1,500/μL -\tplatelets \t>100,000/μL -\ttotal bilirubin \t< 1.5 X institutional upper limit of normal (ULN) -\tAST(SGOT)/ALT(SGPT)\t <2.5 X ULN -\tcreatinine \t< 1.5 X ULN -\tcreatinine clearance \t>30 mL/min/1.73 m2"}

Exclusion criteria

• {"criterion_text":"-Prior treatment with FTD/TPI for mCRC"}
• {"criterion_text":"-Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier."}
• {"criterion_text":"-Participation in another clinical trial with any investigational agents within 30 days prior to study screening"}
• {"criterion_text":"-Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events."}
• {"criterion_text":"-History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab, FTD/TPI, Bevacizumab or components of the DC vaccine."}
• {"criterion_text":"-History of congenital or acquired immunodeficiency, including history of organ transplantation."}
• {"criterion_text":"-Any active inflammatory or autoimmune disease requiring systemic steroids or other immunomodulatory agents"}
• {"criterion_text":"-Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements"}
• {"criterion_text":"-Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix)."}

Primary endpoints

• {"endpoint_text":"-The primary endpoint is Overall Response Rate (ORR) of chemotherapy, defined as the percentage of patients experiencing partial response (PR) or complete response (CR), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, after starting the treatment with the first immunotherapy induction administration.","definition_or_measurement_approach":"ORR is defined as the percentage of patients experiencing partial response (PR) or complete response (CR) according to RECIST v1.1 after starting the first immunotherapy induction administration."}

Secondary endpoints

• {"endpoint_text":"-Progression free survival (PFS): measured as the time from the date of the first immunotherapy induction administration to the date of first progression, or the date of death from any cause, or the date of the last restaging in non-progressed patients","definition_or_measurement_approach":"PFS measured from first immunotherapy induction administration to first progression, death from any cause, or last restaging in non-progressed patients."}
• {"endpoint_text":"-Safety evaluation: all adverse events will be recorded during the observation period (i.e. from the day of the first DC vaccine dose administered in the induction phase up to 30 days after the last dose of chemotherapy), will be reported and graded according to NCI CTCAE 5.0","definition_or_measurement_approach":"All adverse events recorded from first DC vaccine dose in induction phase up to 30 days after last chemotherapy dose and graded per NCI CTCAE v5.0."}
• {"endpoint_text":"-Overall Survival (OS): measured from the start of the induction treatment until the date of death from any cause or the last date on which it was known that the patient was alive","definition_or_measurement_approach":"OS measured from start of induction treatment until death from any cause or last known alive date."}
• {"endpoint_text":"-In vivo immunomonitoring through DTH test; characterization of patient's HLA class I and II and HLA-restricted immune response and definition of the prognostic and predictive role of peripheral immune cell subsets and soluble factors","definition_or_measurement_approach":"In vivo immunomonitoring via DTH test and immunological assays to characterize HLA class I/II, HLA-restricted responses and peripheral immune cell subsets and soluble factors."}
• {"endpoint_text":"-In situ characterization of MSS/pMMR mCRC through NGS and in situ protein validation at the single cell level","definition_or_measurement_approach":"In situ NGS characterization and single-cell level in situ protein validation of MSS/pMMR metastatic colorectal cancer tissue."}

Italy

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

564

Number Of Sites

2

Number Of Participants

36

Primary sponsor

Full Name

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy