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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Jan 2025 → ongoing

Decision date (initial)

2024-11-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Italian Ministry of Health

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

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

Secondary objectives 5

1. Progression-Free survival (PFS)
2. Safety
3. Overall survival (OS)
4. Immunological efficacy
5. In situ protein validation at the single cell level

Conditions and MedDRA coding

Metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participant is willing and able to provide written informed consent for participation in the study.
2. 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
3. Recovery (grade 1 or less by CTCAE 5.0) from all the adverse events related to previous surgery
4. 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
5. Histologically confirmed pMMR or MSS mCRC
6. Male or female, aged ≥ 18 years
7. Life expectancy greater than 12 weeks
8. ECOG performance status <2
9. 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
10. 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.
11. 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
12. 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

Exclusion criteria 9

1. Prior treatment with FTD/TPI for mCRC
2. 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.
3. Participation in another clinical trial with any investigational agents within 30 days prior to study screening
4. 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.
5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab, FTD/TPI, Bevacizumab or components of the DC vaccine.
6. History of congenital or acquired immunodeficiency, including history of organ transplantation.
7. Any active inflammatory or autoimmune disease requiring systemic steroids or other immunomodulatory agents
8. 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
9. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 the first immunotherapy induction administration.

Secondary endpoints 5

1. Progression free survival (PFS): measured as the time from the date of the first immunotherapy induction administration to the date of first progression, or the date of death from any cause, or the date of the last restaging in non-progressed patients
2. Safety evaluation: all adverse events will be recorded during the observation period (i.e. from the day of the first DC vaccine dose administered in the induction phase up to 30 days after the last dose of chemotherapy), will be reported and graded according to NCI CTCAE 5.0
3. Overall Survival (OS): measured from the start of the induction treatment until the date of death from any cause or the last date on which it was known that the patient was alive
4. In vivo immunomonitoring through DTH test; characterization of patient's HLA class I and II and HLA-restricted immune response and definition of the prognostic and predictive role of peripheral immune cell subsets and soluble factors
5. In situ characterization of MSS/pMMR mCRC through NGS and in situ protein validation at the single cell level

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

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

Contact name

Alessandro Passardi

Public contact point

Organisation

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

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications