A Phase II Trial of Neoadjuvant PD-1 Vaccine PD1-Vaxx in Operable MSI High Colorectal Cancer

NCT06692959 | Terminated Phase 2 DMC

• 1 other identifier: 79361
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of Neo-POLEM is to determine the rate of Major Pathological Response (MPR) of \<10% viable tumour cells after administering neoadjuvant PD-1 vaccine IMU-201 (PD1-Vaxx), as measured by percentage change pre- and post-treatment in operable MSI high CRC patients. All patients will be administered three doses of the PD1-Vaxx prior to resection surgery and will be followed up for a minimum of 2 years.

Conditions

Colorectal Cancer

Keywords

PD-1 Vaccine; Operable Colorectal Cancer; Neo-adjuvant

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) rates after administering neoadjuvant PD-1 vaccine

  Proportion of participants with MPR (determined by ≤10% viable tumour cells after receiving PD1-Vaxx).

  At surgery

Secondary Outcomes (8)

• Safety of PD-1 vaccine PD1-Vaxx in the neo-adjuvant setting

  From first vaccine dose until 100 days after the last study treatment

• Rate of complete response after receiving PD1-Vaxx

  At surgery

• Objective response rate

  21 days after last vaccine

• Disease free survival

  From surgery until completion of 2 year follow up

• Overall survival

  From enrolment to completion of 2 years follow up

Study Arms (1)

PD1-Vaxx

EXPERIMENTAL

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.

Drug: PD-1 vaccine IMU-201 (PD1-Vaxx)

Interventions

PD-1 vaccine IMU-201 (PD1-Vaxx) DRUG

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.

PD1-Vaxx

Eligibility Criteria

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

You may qualify if:

• 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.
• Patients must be willing and able to comply with the schedule visits, treatment schedules, laboratory tests and other requirements of the study.
• Target Population
• Histologically confirmed adenocarcinoma cancer of the colon and high rectum.
• ECOG Performance status 0 or 1
• Measurable disease per RECIST 1.1 criteria
• 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...
• In order in to be entered into the study, patients must be classified as MSI-High (confirmation of MMR deficiency or MSI-H).
• Stage II (T3-T4 N0) III (any T, N1 or N2, M0) Colorectal cancer
• Radiological evidence of operable CRC, determined by local MDT, usually CT scan.
• Treatment naive patients (no prior anti CRC therapy).
• Screening laboratory values must meet the following criteria
• Neutrophils ≥ 1.5x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 9.0 g/dl

You may not qualify if:

• 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.
• Distant metastases or peritoneal nodules (M1)
• Active or prior documented autoimmune disease (including inflammatory bowel disease, coeliac disease, and Wegener syndrome).
• 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.
• History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
• If they are positive for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• If they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• 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)).
• 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.
• 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.
• 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.
• 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.
• Systemic antibiotic treatment within 7 days prior to the start of trial treatment.
• Patients with a documented history of pneumonitis, regardless of the cause.

Sponsors & Collaborators

• University of Southampton: lead
• Australasian Gastro-Intestinal Trials Group: collaborator

Study Sites (2)

The Queen Elizabeth Hospital

Adelaide, South Australia, Australia

Location

St John of God Subiaco Hospital

Perth, Western Australia, Australia

Location

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Tony Dhillon

  Royal Surrey Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase II, Bayesian Optimal Design, single arm, one cohort, open label, multi-centre study of neoadjuvant PD-1 vaccine PD1-Vaxx and surgical resection in adult patients with operable MSI-high colorectal cancer.

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 18, 2024
• Study Start: June 16, 2025
• Primary Completion: May 28, 2026
• Study Completion: May 28, 2026
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

AU (2)