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

NCT06522919 | Recruiting Phase 2

• 1 other identifier: IRST153.09
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Colorectal Cancer Metastatic; Microsatellite Stable Colorectal Carcinoma; Refractory Mismatch-repair-proficient (pMMR) Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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 FTD/TPI plus Bevacizumab.

  2 years

Secondary Outcomes (12)

• Progression free survival (PFS)

  2 years

• Safety evaluation

  2 years

• Overall Survival (OS)

  2 years

• In vivo immunomonitoring through DTH test:

  2 years

• Characterization of patient's HLA class I immune response

  2 years

Study Arms (1)

Sequential immunochemotherapy with Pembrolizumab plus DC Vaccine, followed by FTD/TPI + Bevacizumab

EXPERIMENTAL

Induction phase: In the immunological induction phase patients will be given DCs intradermally every week for up to 4 doses and then a further administration after 3 weeks and Pembrolizumab 200 mg IV q3w for up to 3 cycle. Maintenance phase: patients will receive FTD/TPI combined with Bevacizumab.Treatment with FTD/TPI and Bevacizumab will start regardless of the response obtained with the induction combo immunotherapy, and will continue until confirmed disease progression, unacceptable toxicity or withdrawal of the consent by the patient, whichever occurs first.

Biological: Autologous Dendritic Cell (DC) Vaccine

Interventions

Autologous Dendritic Cell (DC) Vaccine BIOLOGICAL

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.

Sequential immunochemotherapy with Pembrolizumab plus DC Vaccine, followed by FTD/TPI + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• The participant may not enter the study if ANY of the following apply:
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (2)

IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l.

Meldola, Forlì Cesena, 47014, Italy

RECRUITING

Pia Fondazione di Culto e Religione Azienda Ospedaliera "Card.G.Panico"

Tricase, Lecce, 73039, Italy

NOT YET RECRUITING

Related Publications (1)

• Passardi A, Sullo FG, Bittoni A, Matteucci L, De Rosa F, Bulgarelli J, Tazzari M, Petrini M, Scarpi E, Testoni S, Miserocchi A, Tartagni O, Zani C, Iaia ML, Toma I, Viola MG, Mita MT, Tamburini E, Ridolfi L. CombiCoR-Vax trial: study protocol for a phase II, single-arm, multicenter trial of sequential pembrolizumab plus dendritic cell vaccine followed by trifluridine/tipiracil and bevacizumab in refractory microsatellite-stable metastatic colorectal cancer. BMC Cancer. 2025 Nov 22;25(1):1921. doi: 10.1186/s12885-025-15371-7.

  PMID: 41275134 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Alessandro Passardi

  IRCCS IRST

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oriana Nanni

CONTACT

0543739266; oriana.nanni@irst.emr.it

Bernadette Vertogen

CONTACT

0544286058; bernadette.vertogen@irst.emr.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label, multicenter phase 2 clinical trial

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 26, 2024
• Study Start: January 7, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

IT (2)