General
PD1-Vaxx is a B-cell immuno-therapy which aims to induce the body to produce polyclonal antibodies that block PD-1 signaling, and thus produce an anticancer effect similar to Keytruda, Opdivo and the other immune checkpoint inhibitor monoclonal antibodies.
Imugene suggest PD1-Vaxx has competitive advantages to existing market drugs as follows:
IMU Trial Approach
Two trials, Imprinter (non-small cell lung cancer) and Neo-POLEM (colorectal cancer).
Imprinter Non-Small Cell Lung Cancer (NSCLC) Trial
Trial Link: https://classic.clinicaltrials.gov/ct2/show/NCT04432207
Description
Investigational Medicinal Product, IMU-201, consists of 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 (Gly-Pro-Ser-Leu), and combined with Water for Injection (WFI) forms the drug product, IMU-201, which becomes PD1-Vaxx when emulsified with excipient Montanide ISA 720 VG.
It is hypothesized that a polyclonal induced B-cell antibody response will be more effective or as effective with improved safety over current monoclonal antibody therapy.
This phase 1/1b study is an open-label dose escalation/dose expansion study designed to assess the safety, tolerability, immunogenicity and efficacy of IMU-201 (PD1-Vaxx). Phase 1 monotherapy dose-escalation of IMU-201 (PD1-Vaxx), will enroll approximately 9-18 patients and establish the optimal monotherapy biological dose (mBOD). Once established, the dose cohort will be expanded to enroll additional 10 patients at the mBOD dose level. Phase 1b, a combination dose-escalation of IMU-201 (PD1-Vaxx) with atezolizumab and with or without chemotherapy, will enroll approximately 18-36 patients and establish the optimal combotherapy biological dose (cBOD). Once established, the dose cohort will be expanded to enroll additional 30 patients at the cBOD dose level.
Neo-POLEM Colo-Rectal Cancer (CRC)
A phase II trial of neoadjuvant PD-1 vaccine IMU-201 (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, IMU-201 (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. The vaccination consists of 100 µg/dose IMU-201 as a 0.5 mL intramuscular (IM) injection. 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 (before the main surgery treatment) PD-1 vaccine IMU-201 (PD1-Vaxx) over a 3-dose schedule in operable MSI high CRC patients
Secondary:
To assess the safety of PD-1 vaccine IMU-201 (PD1-Vaxx) in the neo-adjuvant setting
To assess effects of PD-1 Vaccine IMU-201 (PD1-Vaxx) on viable tumour cells
To report the objective response rate (ORR) of PD-1 vaccine IMU-201 (PD1-Vaxx) in the neo-adjuvant setting
To assess disease free survival (post-surgery) and overall survival
Assessment of complications of surgery
(20min delay)