Intratumoral Flu Vaccine and Pembrolizumab in Colorectal Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zealand University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Nov 2023 → ongoing

Decision date (initial)

2023-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

This study aims to investigate whether a combination of local flu vaccine treatment and immunotherapy will cause tumor regression in patients with pMMR type colorectal cancer.

Secondary objectives 1

1. We will investigate specific safety events during the trial and will characterize the cancer-killing immune cells with different methods as well as characterize the functional changes in the tumor microenvironment

Conditions and MedDRA coding

Colorectal Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Have histologically confirmed localized pMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colorectal carcinoma.
2. Have indication for elective curative intended surgery without neoadjuvant chemotherapy.
3. Be ≥ 18 years of age on the date of signing the informed consent.
4. Provide written informed consent
5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. 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
7. Have adequate kidney function defined as Glomerular filtration rate (GFR) ≥ 60 mL/min or creatinine ≤1.5 X upper limit of normal (ULN)
8. Have adequate liver function defined as: Total bilirubin ≤ 1.5 × ULN Alanine aminotransferase (ALT): ≤ 2.5 × ULN Alkaline phosphatase: ≤ 2.5 × ULN
9. Follow the conditions regarding fertility, pregnancy, and lactation: Female and male participants of reproductive potential (for definition refer to appendix 18) must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving pembrolizumab and for 120 days after the administration.
10. Participants must use (or have their partner use) an acceptable method of contraception, during heterosexual activity, while receiving pembrolizumab and for 120 days after the administration.
11. Women of reproductive potential (WORP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to receiving pembrolizumab.
12. Women must not be breastfeeding.

Exclusion criteria 12

1. 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.
2. Has an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus).
3. 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.
4. 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).
5. 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.
6. 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)
7. Has recently received yellow fever, rabies, BCG, and typhoid (oral) vaccine.
8. Has a history of allergy to study drug components or a history of severe hypersensitivity reaction to any monoclonal antibody
9. Any previous allergic reaction to influenza vaccine or constituents, egg and chicken proteins, neomycin, formaldehyde or octoxinol-9
10. Acute febrile illness
11. Acute infectious disease
12. Highly inflamed gastrointestinal tissue which is ulcerated and bleeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be that 50% or more patients achieve a major pathological response (MPR) that will be defined as < 10 % viable cells corresponding to Mandard tumor regression grade 1-2 (MTRG).

Secondary endpoints 3

1. Specific safety outcomes including tumor site perforation and delay of surgery, and changes in the recovery as assessed by the QoR-15 questionnaire
2. Analysis of tumor samples: Immunohistochemical analysis of CD3+ and CD8+ T cells, spatial protein expression analyses of immune-infiltrated regions of tumors at the different time points, flow cytometry, and full transcriptomic analyses including single cell analysis.
3. Analysis of blood samples: flow cytometry and full transcriptomic analyses including single cell analysis.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zealand University Hospital

Sponsor organisation

Zealand University Hospital

Address

Lykkebaekvej 1

City

Koege

Postcode

4600

Country

Denmark

Scientific contact point

Organisation

Zealand University Hospital

Contact name

Ismail Gögenur

Public contact point

Organisation

Zealand University Hospital

Contact name

Ismail Gögenur

Third parties 1

Locations

1 EU/EEA country · 3 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 12 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