Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Phase I study of NOX66 in combination with radiotherapy in patients with late-stage metastatic castrate resistant prostate cancer (DARRT-1 Study) (#332)

Gisela Mautner 1 , Anne Capp 2 , Nana Chikhladze 3 , Tamar Melkadze 4 , Zaza Mezvrishvili 5 , Marinella Messina 1 , Greg van Wyk 1
  1. Noxopharm Limited, Sydney, NSW, Australia
  2. Genesis Cancer Care, Newcastle, New South Wales, Australia
  3. Institution Tbilisi State Medical University The First University Clinic, Tbillisi, Georgia
  4. Research Institute of Clinical Medicine, Tbillisi, Georgia
  5. Al. Tsulukidze National Center of Urology, Tbillisi, Georgia

Aims: The DARRT-1 (Direct and Abscopal Response to Radiotherapy) study aims to determine the tolerability and examine signals of efficacy of NOX66 in combination with low-dose radiotherapy in men with late-stage metastatic castrate resistant prostate cancer (mCRPC).

Methods: A Phase 1b study (protocol: NOX66-002A) with a dose-finding arm (4-6 patients per cohort; 400 mg, 800 mg or 1200 mg NOX66 daily for 14 days) and expansion arm (n=12; 1200 mg NOX66 daily for 14 days). All patients receive NOX66 and radiotherapy (20) in 5 fractionated doses and are assessed at 6, 12 and 24 weeks with follow up to 24 months. Objectives include frequency of treatment-emergent adverse events (TEAEs) and radiographic response (RECIST v1.1), prostate specific antigen (PSA) response (≥50% reduction),and pain response..

Results: Of the 14 patients in the dose escalation arm, 2 progressed early and were replaced and 10 completed 24 weeks. Two patients each in the 800 mg and 1200 mg cohorts achieved PSA response at 12 weeks; one patient in each cohort maintained response through 24 weeks. Seven patients achieved a clinically meaningful pain response at 12 weeks; 5 patients maintained response through 24 weeks and 2 patients were pain-free at 24 weeks. Eight patients (57%) maintained radiographic response from 12 to 24 weeks (PR = 1 patient, SD = 7 patients). The patient with an overall PR had a 50% size reduction in both the irradiated index lesion and a distant lesion. TEAEs considered related to NOX66 alone were mild (Grade 1) cases of dry mouth and oral mucositis; mild (Grade 1) fatigue was considered related to both NOX66 and radiation. None of the 12 Grade >3 TEAEs were considered related to study drug. The results for the dose escalation arm will be presented at COSA 2019.