Date: 2014-05-28
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Debiopharm (Switzerland)
Product: Debio 0932
Action
mechanism: Debio 0932 is an oral second-generation HSP90 inhibitor, which has shown extended tumour retention, blood-brain-barrier penetration, and promising anti-tumour activity both as monotherapy and in combination against a broad range of tumours in pre-clinical models.
Debio 0932 potently inhibits tumour growth in subcutaneous xenograft models of a number of solid and haematological malignancies, including models of NSCLC which harbour mutations conferring acquired or primary erlotinib resistance. Furthermore, Debio 0932 is able to extend animal survival in models of brain metastasis due to its ability to cross the blood-brain barrier, and it enhances the activity of several standard-of-care agents in animal models of cancer.
Disease: solid tumours
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 28, 2014, Debiopharm, a Swiss-based global biopharmaceutical company developing prescription drugs that target unmet medical needs as well as companion diagnostics, announced that new data on Debio 0932 (Hsp90 inhibitor) will be presented at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago. Debio 0932 is a small oral molecule inhibitor of heat shock protein 90 (HSP90). Inhibition of HSP90 results in the degradation of oncoproteins that drive malignant progression and leads to cell death. Debio 0932 has shown efficacy in various mouse tumor xenografts and exhibits sustained tumor retention. Debio 0932 has been investigated in one phase I clinical study. Two phase I/II studies are ongoing in Europe in advanced non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) in combination with SOC and everolimus, respectively. Abstracts presented at ASCO: Final results from the phase I study expansion cohort of Debio 0932, an oral HSP90 inhibitor, in patients with solid tumors (#2550) and The HALO study: A phase I-II of the oral HSP90 inhibitor Debio 0932 in combination with SOC in first- and second-line therapy of advanced NSCLC (#TPS2632). * On June 6, 2012, Debiopharm has presented results of a Phase I open-label dose-escalation study with Debio 0932, an oral Heat Shock Protein 90 (HSP90) inhibitor in clinical development as an anti-cancer agent. The study was designed to determine the maximum tolerated dose of Debio 0932. During the study, Debio 0932 was administered orally every other day or once daily at a starting dose of 50mg. Patients receiving a daily dose remained on treatment for an average of 81 days, the former for 76 days. Debio 0932 monotherapy was generally well tolerated in doses up to 1600mg every other day and 1000mg daily. It showed promising signs of anti-tumour activity in patients with advanced solid tumours, especially lung cancer. * On February 16, 2012, Debiopharm and Curis have announced that Debiopharm has begun treating patients in a Phase Ib clinical trial of Heat Shock Protein 90 (HSP90) inhibitor Debio 0932. Debiopharm recently successfully completed a Phase Ia dose escalation study with Debio 0932 and has indicated that it expects to initiate a combination Phase I/II study in non-small cell lung cancer patients in the second quarter of 2012. Debiopharm initiated a Phase I clinical trial in April 2010 that was designed to evaluate the maximum tolerated dose and safety of Debio 0932. The first part of the study (Phase Ia), an open-label, multi-center dose escalation trial evaluating the safety and tolerability of escalating multiple dose levels of Debio 0932 given daily or every other day as a single agent by oral administration in patients suffering from advanced solid tumours, was recently completed. Debio 0932 was generally well tolerated, with no evidence of ocular or liver toxicity, and showed promising signs of efficacy in patients with advanced solid tumours. The recommended dose, established at 1000mg every day, will be tested in additional patients during the expansion phase (Phase Ib) of the ongoing Phase I study. Details from the Phase Ia portion of the study will be presented at a medical conference in 2012.
During the study, adverse events observed included constipation, diarrhea, nausea, vomiting, asthenia, and decreased appetite, however there was no apparent relation between the dose of Debio 0932 and the occurrence of these adverse events. No ocular or cardiac toxicity was observed.
Out of the 50 patients enrolled in the study, 45 were evaluable for anti-tumour activity assessment. Partial responses were observed in a patient with non-small cell lung cancer (NSCLC) and in a patient with breast cancer. Among seven other patients with lung cancer, four had stable disease and three had progressive disease.
The recommended dose for the Phase 2 study has been established at 1000mg per day and will be tested in an additional 30 patients in an on-going expansion study. A Phase I-II study of Debio 0932 in combination with standard of care in the first- and second-line treatment of non-small cell lung cancer is planned.
