Trial Title:
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
NCT ID:
NCT06522919
Condition:
Colorectal Cancer Metastatic
Microsatellite Stable Colorectal Carcinoma
Refractory Mismatch-repair-proficient (pMMR) Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single-arm, open-label, multicenter phase 2 clinical trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Autologous Dendritic Cell (DC) Vaccine
Description:
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.
Arm group label:
Sequential immunochemotherapy with Pembrolizumab plus DC Vaccine, followed by FTD/TPI + Bevacizumab
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.
Detailed description:
Metastatic colorectal cancer (mCRC) remains an incurable disease characterized by a poor
prognosis. Recently, in the global phase 3 SUNLIGHT (NCT04737187) study, adding
Bevacizumab to Trifluridine/Tipiracil (FTD/TPI) in the treatment of refractory mCRC
significantly improved overall survival. Therefore, this combination regimen is going to
become the new standard of care for refractory mCRC. Immune checkpoint inhibitors (ICIs),
including Pembrolizumab, have shown excellent results in MSI-H or dMMR mCRC, and recent
trials evaluating both concomitant and sequential chemoimmunotherapy in MSS/pMMR mCRC (in
particular ATEZOTRIBE and MAYA trials), have shown promising results. Since 2001, we have
treated more than 80 advanced melanoma patients with a tumor lysate loaded autologous DC
vaccine, observing a clinical benefit of 54.1% and, more importantly, an ORR of 63.6% to
subsequent chemotherapy, suggesting that immunotherapy might improve the activity of
sequential chemotherapy. Moreover, our team has recently concluded the first step of 2
ongoing clinical studies with DC vaccine administration, in radically resected mCRC and
metastatic mesothelioma patients - showing that the vaccine was safe and promoted
immunological responses that allowed it to continue with patients enrollment.
Criteria for 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l.
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Contact:
Last name:
Oriana Nanni
Phone:
+390543739266
Email:
oriana.nanni@irst.emr.it
Contact backup:
Last name:
Bernadette Vertogen
Phone:
+390544286058
Email:
bernadette.vertogen@irst.emr.it
Investigator:
Last name:
Alessandro Passardi, Study Chair
Email:
Principal Investigator
Facility:
Name:
Pia Fondazione di Culto e Religione Azienda Ospedaliera "Card.G.Panico"
Address:
City:
Tricase
Zip:
73039
Country:
Italy
Contact:
Last name:
Emiliano Tamburini, MD
Phone:
+390833773111
Email:
e.tamburini@piafondazionepanico.it
Start date:
September 1, 2024
Completion date:
September 1, 2026
Lead sponsor:
Agency:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Agency class:
Other
Source:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06522919
