Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Combination of Avelumab with Peptide Receptor Radionuclide Therapy (PRRT) or Conventional Fractionated Radiotherapy (RT) in Metastatic Merkel Cell Carcinoma (mMCC) [GoTHAM study] (#287)

Shahneen Sandhu 1 , Richard Tothill 2 , Richard Scolyer 3 , Alexander Guminski 4 , Jürgen Becker 5 , Michael Poulsen 6 , Victoria Atkinson 7 , Paul Neeson 1 , Mark Shackleton 8 , David Pattison 9 , Narelle Williams 10 , Elizabeth Paton 10
  1. Peter MacCallum Cancer Centre, Melbourne, VIC
  2. University Of Melbourne, Melbourne, VIC
  3. Melanoma Institute Australia, Sydney, NSW, Australia
  4. Royal North Shore Hospital , Sydney, NSW
  5. German Cancer Research Centre, Heidelberg, Germany
  6. University of Queensland/Princess Alexandra Hospital, Brisbane, QLD
  7. Princess Alexandra Hospital , Brisbane, QLD
  8. The Alfred, Melbourne, VIC
  9. Royal Brisbane and Women's Hospital, Brisbane, QLD
  10. Melanoma and Skin Cancer Trials, North Sydney, NSW, Australia

Background:

Despite recent advances with immune checkpoint inhibitors, such as avelumab which has changed the treatment landscape for metastatic Merkel Cell Carcinoma (mMCC), many mMCC patients who attained an initial response exhibit acquired resistance within 1 year. Therefore, novel treatment combinations are needed to improve patient outcome. MCC is an exquisitely radiosensitive tumour and there is emerging data supporting the role of radiation in inducing immunogenic cell death and therefore potentially improving the anti-tumour efficacy when combined with immune checkpoint inhibitors. Peptide receptor radionuclide therapy (PRRT) is used in first-line treatment for neuroendocrine tumours (NETs), by delivering radiation to somatostatin receptor (SSTR) expressing tumour cells. Most NETs, including MCC, express SSTR. Therefore, MCC tumours are ideal candidates for PRRT, and immune checkpoint inhibitor combination approaches with PRRT are highly attractive.

Methods:

The GoTHAM trial is intended as a signal-seeking and biomarker study. It is designed as a prospective, open-labelled, multi-institutional, three-arm, phase Ib/II trial that will evaluate the safety and anti-tumour activity of 177Lu-DOTA-octreotate (LuTate) or external beam radiation therapy (EBRT) in combination with avelumab in patients with mMCC. The primary objective is to evaluate the anti-tumour activity as reflected by PFS rate at 12 months.

Results:

It is anticipated that the trial will open across Australia at 8-10 sites to commence recruitment by the final quarter of 2019 with the last patient last visit expected in May 2023.

Conclusion:

The findings of this trial will shape the design of future formal randomised phase II trials of avelumab in combination with LuTate or conventional fractionated RT in patients with mMCC.