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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06692959




Registration number
NCT06692959
Ethics application status
Date submitted
7/11/2024
Date registered
18/11/2024
Date last updated
2/05/2025

Titles & IDs
Public title
A Phase II Trial of Neoadjuvant PD-1 Vaccine PD1-Vaxx in Operable MSI High Colorectal Cancer
Scientific title
A Phase II Trial of Neoadjuvant PD-1 Vaccine PD1-Vaxx in Operable MSI High Colorectal Cancer
Secondary ID [1] 0 0
79361
Universal Trial Number (UTN)
Trial acronym
Neo-POLEM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PD-1 vaccine IMU-201 (PD1-Vaxx)

Experimental: PD1-Vaxx - All patients will be administered PD1-Vaxx intramuscularly into the deltoid region of the upper arm on days 1,15 and 29. Patients will undergo resection surgery within 21 days, but up to 42 days of completing trial treatment.


Treatment: Drugs: PD-1 vaccine IMU-201 (PD1-Vaxx)
Investigational Medicinal Product (IMP) PD1-Vaxx is supplied as lyophilized drug substance APi2568, which is a B-cell epitope (amino acids 92-110 from PD-1) linked to a promiscuous T-cell epitope (amino acid residues 288-302 from measles virus fusion protein) via a 4-amino acid linker (G-P-S-L). IMU-201 is combined with water for Injection (WFI) and is emulsified with Montanide ISA 51 VG adjuvant to produce PD1-Vaxx.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Pathological Response (MPR) rates after administering neoadjuvant PD-1 vaccine
Timepoint [1] 0 0
At surgery
Secondary outcome [1] 0 0
Safety of PD-1 vaccine PD1-Vaxx in the neo-adjuvant setting
Timepoint [1] 0 0
From first vaccine dose until 100 days after the last study treatment
Secondary outcome [2] 0 0
Rate of complete response after receiving PD1-Vaxx
Timepoint [2] 0 0
At surgery
Secondary outcome [3] 0 0
Objective response rate
Timepoint [3] 0 0
21 days after last vaccine
Secondary outcome [4] 0 0
Disease free survival
Timepoint [4] 0 0
From surgery until completion of 2 year follow up
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
From enrolment to completion of 2 years follow up
Secondary outcome [6] 0 0
Claviend-Dindo
Timepoint [6] 0 0
30 days post surgery
Secondary outcome [7] 0 0
Health-related quality of life
Timepoint [7] 0 0
21 days after last vaccine
Secondary outcome [8] 0 0
Health-related quality of life
Timepoint [8] 0 0
21 days after last vaccine

Eligibility
Key inclusion criteria
1. Patients must have signed and dated a written informed consent form. This must be performed before the performance of any protocol related procedures that are not part of the normal care.
2. Patients must be willing and able to comply with the schedule visits, treatment schedules, laboratory tests and other requirements of the study.

Target Population
3. Histologically confirmed adenocarcinoma cancer of the colon and high rectum.
4. ECOG Performance status 0 or 1
5. Measurable disease per RECIST 1.1 criteria
6. Tumour tissue from a colonoscopy must be provided for biomarker analysis. Archival tumour tissue is mandatory for biomarker analysis. If no sample is available, patients will have the option to agree to acquisition of additional tumour tissue during the screening period for future biomarker analyses...
7. In order in to be entered into the study, patients must be classified as MSI-High (confirmation of MMR deficiency or MSI-H).
8. Stage II (T3-T4 N0) III (any T, N1 or N2, M0) Colorectal cancer
9. Radiological evidence of operable CRC, determined by local MDT, usually CT scan.
10. Treatment naive patients (no prior anti CRC therapy).
11. Screening laboratory values must meet the following criteria

1. Neutrophils = 1.5x 109/L
2. Platelets = 100 x 109/L
3. Haemoglobin = 9.0 g/dl
4. Serum creatinine = 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 'CrCl' > 50 mL/min (using the Cockcroft Gault formula):

* Female CrCl = (140 - age in years) x weight (kg) x 1.04 serum creatinine (µmol/l)
* Male CrCl = (140 - age in years) x weight (kg) x 1.23 serum creatinine in µmol
5. Total bilirubin = 1.5 x ULN; for patients with documented/suspected Gilbert's disease, bilirubin =3 x ULN
6. AST =1.5 x ULN
7. ALT =1.5 x ULN

Age and Reproductive Status
12. Age = 18 years
13. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug.
14. Women must not be breastfeeding.
15. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception, as indicated in the informed consent form. Contraception must be used for the duration of treatment and for a period of 180 days after last dose of study drug.
16. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception, as indicated in the informed consent form for a period of 180 days. Men who are sexually active with WOCBP must continue contraception for 180 days after the last dose of investigational drug (combination or monotherapy). In addition, male patients must be willing to refrain from sperm donation during this time.
17. Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
18. History of severe allergic reactions (i.e., Grade 4 allergy, anaphylactic reaction from which the patient did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the PD-1 vaccine formulations.
19. Distant metastases or peritoneal nodules (M1)
20. Active or prior documented autoimmune disease (including inflammatory bowel disease, coeliac disease, and Wegener syndrome).
21. Any concurrent chemotherapy or biologic or hormonal therapy for CRC treatment. Concurrent use of hormones for non-cancer- related conditions (e.g. insulin for diabetes and hormone replacement therapy) is acceptable.
22. History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
23. If they are positive for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
24. If they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
25. Receipt of live, attenuated vaccine within 28 days prior to the first dose of PD-1 vaccine PD1-Vaxx (patients, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of Investigational Medicinal Product (IMP)).
26. Other invasive malignancy within two years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured. Cancer patients with incidental histological findings of prostate cancer (tumour/node/metastasis stage of T1a or T1b or prostate-specific antigen ?10) who have not received hormonal treatment may be included.
27. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the patient to give written informed consent.
28. Any condition that, in the opinion of the investigator or sponsor, would interfere with the evaluation of the investigational product or interpretation of patient safety or study results.
29. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisolone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisolone equivalents are permitted in the absence of active autoimmune disease.
30. Systemic antibiotic treatment within 7 days prior to the start of trial treatment.
31. Patients with a documented history of pneumonitis, regardless of the cause.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/05/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2029
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Surrey
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Coventry
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
University of Southampton
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australasian Gastro-Intestinal Trials Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tony Dhillon
Address 0 0
Country 0 0
Phone 0 0
023 8120 5154
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06692959