Combination immunotherapy and chemotherapy for advanced colorectal cancer

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)

This study is testing a new treatment for patients with advanced colorectal cancer that combines immunotherapy and chemotherapy to see if it can help them better than current options.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS (other)
• Drugs / interventions: Pembrolizumab, Bevacizumab, chemotherapy, immunotherapy
• Locations: 2 sites (Meldola, Forlì Cesena and 1 other locations)
• Trial ID: NCT06522919 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a novel treatment approach for patients with refractory metastatic colorectal cancer that is mismatch-repair proficient or microsatellite stable. It involves an initial combination of Pembrolizumab and a dendritic cell vaccine to stimulate the immune response, followed by maintenance therapy with Trifluridine/Tipiracil and Bevacizumab. The study aims to assess both the clinical efficacy and immunological activity of this sequential treatment strategy. The trial is single-arm and open-label, conducted across multiple centers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed pMMR or MSS metastatic colorectal cancer.

Not a fit: Patients with prior treatment involving multiple chemotherapy regimens or those with non-measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with advanced colorectal cancer.

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy approaches in colorectal cancer, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

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.
* Any active inflammatory or autoimmune disease requiring systemic steroids or other immunomodulatory agents
* 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).

Where this trial is running

Meldola, Forlì Cesena and 1 other locations

• IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l. — Meldola, Forlì Cesena, Italy (RECRUITING)
• Pia Fondazione di Culto e Religione Azienda Ospedaliera "Card.G.Panico" — Tricase, Lecce, Italy (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Alessandro Passardi — IRCCS IRST
• Study coordinator: Oriana Nanni

Conditions: Colorectal Cancer Metastatic, Microsatellite Stable Colorectal Carcinoma, Refractory Mismatch-repair-proficient Metastatic Colorectal Cancer