Invited Speaker Melbourne Immunotherapy Spring Symposium 2025

Building the Bridge of Translation and Traversing it with Laboratory-informed Clinical Trials (129817)

Robert Ramsay 1
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Much is said about research translation advocating for laboratory research to be embedded into and informing clinical trials. Agreed that these are demanding ambitions, but they are genuinely achievable with planning, networking and patience. At Peter Mac my team and others have developed a model that promotes interactions between the clinical and laboratory-based teams to advance coordinated clinical trials as investigator-initiated, research-sub study supported and international, multicentre phase 3 clinical trials. That the immune system is likely to be key to maximizing the outcomes of clinical trials, in this presentation several examples of this coordination will be provided. (1) Peritoneal metastasis is typically fatal without extensive abdominal surgery, but the surgical process itself has the potential to exacerbate tumour cell spread and implantation during surgical excision of primary abdominal cancersa. The PERIPROTECT trial grew from extensive research in mice and pigs leading to the evaluation humidifying gas during surgery reducing inflammation and peritoneal damage. The data generated has led to practice change in laparoscopic surgeryb. (2) The combination of immune checkpoint therapy plus radiation therapy required a window of opportunity within the boundaries of standard of care. We identified such a window allowing the use of an anti-PDL-1 antibody immediately after chemo-radiotherapy and before pelvic surgery in patients with locally advanced rectal cancer, the AVEREC trialc. We had abundant lab data with co-culture studies with tumour infiltrating lymphocytes and tumouroids to convince a Pharma partner that this was promising clinical avenued. Just published, this study showed marked improvement in pathological responses and immune enhancement and is set to initiate a follow up trial. (3) My team developed a novel T-cell mediated therapeutic vaccine against the transcription factor MYB in concert with anti-PD1 antibody showing cures in mice with aggressive colon tumors as well as clearance of adenomas. This paved the way for the MYPHISMO trial in patients with MYB-expressing colorectal and adenoid cystic carcinomase. It required a unique clinical trial protocol allowing safety and investigational studies to be performed. (4) Finally, Peter Mac cares for patients with rare but challenging anal squamous cell carcinomas where not much has changed in their management for decades. Our next proposed trial is built upon lab data with a new photodynamic agent with anti-PD-1 tested in a bespoke immunocompetent mouse model plus our large bank of anal SCC tumouroids. Another related trial has shown promising safety and pain data and we are in the process of putting all the parts of the trial documentation together with a plan to start this trial by the end of the year.

  1. Cortes-Guiral, et al (2021) Primary and metastatic peritoneal surface malignancies. Nature Reviews Disease Primers: 7, 91
  2. Sampurno et al (2022) Effect of surgical humidification on inflammation and peritoneal trauma in colorectal cancer surgery: a randomized controlled trial. Annals of Surgical Oncology 29:7911-792
  3. Michael et al (2025) The Ave-Rec trial: Phase II trial of PDL1/PD-1 blockade with Avelumab post Chemoradiotherapy for locally advanced resectable T3B-4/N1-2 Rectal cancer. Clinical Cancer Research 31: 3452–3462.
  4. Kong et al (2018). Tumor Infiltrating Lymphocyte Function Predicts Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. J. Clinical Oncology Precision Oncology. 2: 1-15
  5. Pham et al (2019) First-in-human phase I clinical trial of a combined immune modulatory approach using TetMYB vaccine and Anti-PD1 antibody in patients with advanced solid cancer including colorectal or adenoid cystic carcinoma: The MYPHISMO study protocol (NCT03287427). Contemporary Clinical Trials Communications. 16: 100409