Neo-POLEM

Title

A phase II trial of neoadjuvant PD-1 vaccine (PD1-Vaxx) in operable MSI high colorectal cancer (CRC)

Description

Early stage colon cancer that has spread to the local lymph nodes is best treated with surgery and chemotherapy, however, half of patients treated will have subsequent recurrence of their cancer. If this happens the cancer is often incurable.

About 1 in 7 colon cancer have ‘defective mismatch repair’ and recent small trials of immunotherapy drugs appear to work exceptionally well in this subtype of cancer. In Neo-POLEM we will use a vaccine approach that is hoped to have a durable effect. The vaccine, PD1-Vaxx, is designed to work by stimulating the immune system to attach the patient’s cancer and it’s predicted that this subtype of cancer may be particularly sensitive to this approach.

Neo-POLEM aims to recruit a maximum of 44 patients in total, 24 in the UK from 3 NHS sites and 20 in Australia. Participants in the study will receive 3 vaccinations, once every 2 weeks over a 6 week period. Following treatment patients will undergo standard care surgery and following this will be followed up for a maximum of two years.

Objectives

Primary:

• To determine major pathological response rates after administering neoadjuvant PD-1 vaccine PD1-Vaxx over a 3-dose schedule in operable MSI high CRC patients

Secondary:

• To assess the safety of PD-1 vaccine in the neo-adjuvant setting
• Rate of complete response (defined as no viable tumour cells) after receiving PD1-Vaxx
• To report the objective response rate (ORR) of PD-1 vaccine PD1-Vaxx in the neo-adjuvant setting
• To assess disease free survival (post-surgery) and overall survival
• Assessment of complications of surgery

Tertiary:

Future exploratory endpoints will include translational work looking at immune related outcomes in MSI-High CRC pre- and post-anti PD-1 vaccine IMU-201 (PD1-Vaxx)

• Profiling of circulating and tumour infiltrating immune cell populations
• Tumour phenotyping
• TIL gene expression analysis
• Tumour sequencing and prediction of neo-epitopes
• Tissue for tissue microarray (TMA (paired))
• Profile of gut microbiome pre and post treatment

Trial Design

Open label, multi-centre phase II Bayesian optimal design

Trial Status

In set-up

Population

Patients due to receive neoadjuvant treatment of operable MSI-H colon cancer (CRC)

Funder

Imugene