Sequential immunochemotherapy treatment with Pembrolizumab plus Dendritic Cell (DC) Vaccine followed by Trifluridine/Tipiracil plus Bevacizumab in refractory mismatch-repair-proficient (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer

Trial details

Who runs it

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

Trial code

EU 2024-514053-30-00

Record updated

2026. április 27.

Original description

The primary objective is the clinical activity of the proposed sequential immunotherapy treatment with Pembrolizumab plus DC Vaccine, followed by FTD/TPI plus Bevacizumab.Read full original descriptionShow less

The primary objective is the clinical activity of the proposed sequential immunotherapy treatment with Pembrolizumab plus DC Vaccine, followed by FTD/TPI plus Bevacizumab.

Inclusion: Participant is willing and able to provide written informed consent for participation in the study; 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; 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; Patients must have normal organ and marrow function as defined below: - leukocytes >3,000/μL - absolute neutrophil count >1,500/μL - platelets >100,000/μL - total bilirubin < 1.5 X institutional upper limit of normal (ULN) - AST(SGOT)/ALT(SGPT) <2.5 X ULN - creatinine < 1.5 X ULN - creatinine clearance >30 mL/min/1.73 m2; 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; Recovery (grade 1 or less by CTCAE 5.0) from all the adverse events related to previous surgery; 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; Histologically confirmed pMMR or MSS mCRC; Male or female, aged ≥ 18 years; Life expectancy greater than 12 weeks; ECOG performance status <2; 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.

Exclusion: Prior treatment with FTD/TPI for mCRC; 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; Participation in another clinical trial with any investigational agents within 30 days prior to study screening; 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; 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); History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab, FTD/TPI, Bevacizumab or components of the DC vaccine; History of congenital or acquired immunodeficiency, including history of organ transplantation; Any active inflammatory or autoimmune disease requiring systemic steroids or other immunomodulatory agents; 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.

EU CTIS 2024-514053-30-00