First-in-human phase I clinical trial of a combined immune modulatory approach using TetMYB vaccine and Anti-PD-1 antibody in patients with advanced solid cancer including colorectal or adenoid cystic carcinoma: The MYPHISMO study protocol (NCT03287427)

Toan Pham; Lloyd Pereira; Sara Roth; Laura Galletta; Emma Link; Tim Akhurst; Ben Solomon; Michael Michael; Phillip Darcy; Shienny Sampurno; Alexander Heriot; Robert Ramsay; Jayesh Desai

doi:10.1016/j.conctc.2019.100409

First-in-human phase I clinical trial of a combined immune modulatory approach using TetMYB vaccine and Anti-PD-1 antibody in patients with advanced solid cancer including colorectal or adenoid cystic carcinoma: The MYPHISMO study protocol (NCT03287427)

Contemp Clin Trials Commun. 2019 Jul 10:16:100409. doi: 10.1016/j.conctc.2019.100409. eCollection 2019 Dec.

Authors

Toan Pham^{1

2

3

4}, Lloyd Pereira¹, Sara Roth¹, Laura Galletta¹, Emma Link¹, Tim Akhurst⁵, Ben Solomon^{3

6}, Michael Michael^{3

6}, Phillip Darcy¹, Shienny Sampurno¹, Alexander Heriot^{1

2

3

4}, Robert Ramsay^{1

3

7}, Jayesh Desai^{3

6}

Affiliations

¹ Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
² Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
⁴ Department of Surgery, University of Melbourne, Melbourne, Australia.
⁵ Division of Medical Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁶ Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁷ Department of Pathology, University of Melbourne, Melbourne, Australia.

Abstract

Background: MYB is a transcription factor that is overexpressed in colorectal cancer (CRC) and also a driver mutation in adenoid cystic carcinoma (AdCC). Therefore, the MYB protein is an ideal target to vaccinate against to aid recruitment of tumour infiltrating lymphocytes (TILs) against these tumours. The Peter MacCallum Cancer Centre (Melbourne, Australia) has engineered a DNA vaccine, TetMYB, based on the pVAX1 plasmid vector carrying a fusion construct consisting of the universal tetanus toxin T-cell epitopes flanking an inactivated MYB gene.

Methods: This prospective first-in-human phase I single-arm multi-centre clinical trial involves patients with metastatic CRC or AdCC. Stage 1 will evaluate the safety profile of escalating doses of TetMYB vaccine, given sequentially and in combination with an anti-PD-1 inhibitory antibody, to determine the maximum tolerated dose (MTD). Stage 2 will assess the MTD in an expanded cohort. The calculated sample size is 32 patients: 12 in Stage 1 and 20 in Stage 2. The expected total duration of the trial is 3 years with 15 months of recruitment followed by a minimum of 18 months follow-up.

Discussion: MYB transcription factor is aberrantly overexpressed in a range of epithelial cancers, not limited to the above tumour types. Based on promising pre-clinical data of vaccine-induced tumour clearance and establishment of anti-tumour memory, we are embarking on this first-in-human trial. If successful, the results from this trial will allow progression to a Phase II trial and validation of this breakthrough immunotherapeutic approach, not only in CRC and AdCC, but other MYB over-expressing cancers.

Trial registration: ClinicalTrials.gov ID: NCT03287427. Registered: September 19, 2017.

Keywords: Adenoid cystic carcinoma; Cancer vaccine; Colorectal neoplasms; Glandular and epithelial neoplasms; Immune checkpoint therapy; Immunotherapy.

Associated data

ClinicalTrials.gov/NCT03287427