Combining Intratumoral Flu Vaccine and Systemic Pembrolizumab in Patients With Early pMMR Colorectal Cancer

NCT05909423 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2023-503228-17-00
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Immune checkpoint inhibitor (ICI) treatment has produced striking results in patients with colorectal cancer (CRC) of the subtype deficient mismatch repair (dMMR). The majority of patients, however, have proficient MMR (pMMR) tumors, with limited effect of ICIs. The key difference between dMMR and pMMR tumors is the infiltration of cytotoxic T-cells. dMMR tumors have increased infiltration and thus increased efficacy from ICI treatment. The investigators conducted a proof of concept study where the investigators applied an intratumoral (IT) unaltered flu vaccine in ten patients with non-metastatic pMMR CRC. The intervention increased infiltration of cytotoxic T-cells and the immune checkpoint PD-L1, suggesting that IT flu vaccine primes pMMR tumors to ICI treatment. The investigators aim to test the combination of IT flu vaccine and ICI treatment in patients with non-metastatic pMMR CRC in a new trial. The hypothesis is that IT flu vaccine and ICI treatment will synergistically to induce cancer cell death.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological response

  The primary endpoint will be the percent of viable tumor cells in the resected specimen. Partial response will be defined as at least 30% tumor regression and major pathological response (MPR) will be defined as \< 10 % viable cells corresponding to Mandard tumor regression grade 1-2

  Day 30-35

Secondary Outcomes (3)

• Number of participants with specific treatment-related adverse events as assessed by CTCAE v4.0"

  Day 0-365

• Tumor microenvironment

  Day 0-35

• Analysis of perturbations in the immune activity with a focus on effector and memory CD8+ T cells

  Day 0-35

Study Arms (1)

Treatment arm

EXPERIMENTAL

Intratumoral flu vaccine treatment Systemic single dose pembrolizumab treatment

Drug: Influenza vaccine; Drug: Pembrolizumab

Interventions

Influenza vaccine DRUG

Intratumoral influenza vaccine treatment, administered via endoscopic procedure

Treatment arm

Pembrolizumab DRUG

Single dose pembrolizumab treatment

Treatment arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically confirmed localized pMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colorectal adenocarcinoma.
• Have indication for elective curative intended surgery without neoadjuvant therapy.
• Be ≥ 18 years of age on the date of signing the informed consent.
• Provide written informed consent
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have adequate bone marrow function:
• Hemoglobin ≥ 6.2 mmol/L or ≥ 10 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Have adequate kidney function defined as Glomerular filtration rate (GFR) ≥ 60 mL/min or creatinine ≤1.5 X upper limit of normal (ULN)
• Have adequate liver function defined as:
• Total bilirubin ≤ 1.5 × ULN
• Alanine aminotransferase (ALT): ≤ 2.5 × ULN
• Alkaline phosphatase: ≤ 2.5 × ULN
• Follow the conditions regarding fertility, pregnancy, and lactation:

You may not qualify if:

• Has any serious or uncontrolled medical disorder that, in the opinion of the investigator or treating physician, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Has an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus).
• Has received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody/drug specifically targeting T cell co-stimulation or checkpoint pathways.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected).
• Has a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Has received live vaccines within 30 days prior to first dose trial treatment (Examples of live vaccines include, but are not limited to: measles, mumps, rubella, chickenpox,
• Has recently received yellow fever, rabies, BCG, and typhoid (oral) vaccine.
• Has a history of allergy to study drug components or a history of severe hypersensitivity reaction to any monoclonal antibody
• Any previous allergic reaction to influenza vaccine or constituents, egg and chicken proteins, neomycin, formaldehyde or octoxinol-9
• Acute febrile illness
• Acute infectious disease
• Highly inflamed gastrointestinal tissue which is ulcerated and bleeding

Sponsors & Collaborators

• Zealand University Hospital: lead
• Slagelse Hospital: collaborator

Study Sites (1)

Center for Surgical Science, Department of Surgery, Zealand University Hospital

Koege, Region Sjælland, 4600, Denmark

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Influenza Vaccines; pembrolizumab

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)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Central Study Contacts

Ismail Gögenur, Professor, DMSc

CONTACT

26336426; igo@regionsjaelland.dk

Mikail Gögenur, MD

CONTACT

31429929; mgog@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, DMSc

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 18, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2028
• Last Updated: June 18, 2023

Record last verified: 2023-06

Locations

DK (1)