Sequential Immunochemotherapy Treatment with Pembrolizumab Plus Dendritic Cell (DC) Vaccine Followed by Trifluridine/Tipiracil (FTD/TPI) Plus Bevacizumab in Refractory Mismatch-repair-proficient (pMMR) or Microsatellite-stable (MSS) Metastatic Colorectal Cancer (CombiCoR-Vax)
Single-arm, open-label, multicenter phase 2 clinical trial evaluating the clinical and the immunological activity of an innovative strategy with an induction combo immunotherapy (Pembrolizumab plus DC Vaccine) followed by a maintenance chemotherapy (FTD/TPI plus Bevacizumab) in patients with refractory MSS/pMMR metastatic colorectal cancer.
• Be willing and able to provide written informed consent.
• 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 Criteria:
• 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 1-2 chemotherapy regimens in an advanced setting, 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 OR 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 and all male patients must accept and be compliant with a highly effective contraceptive method
• Participant is willing and able to give informed consent for participation in the study.