Clinical Trials

* On May 28, 2015, Onxeo announced clinical data from studies supporting of the potential of belinostat in multiple orphan oncology indications. Results of the Phase I/II trial will be presented during a poster session and further reviewed during a separate poster discussion session, both on Sunday, May 31, at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 29-June 2 in Chicago, IL. The completed Phase I/II, open-label, multi-center, dose-escalation study evaluated the safety and efficacy of belinostat in combination with standard chemotherapy doxorubicin in a total of 41 patients and found the combination was well-tolerated and exhibited anti-cancer activity in 12 of 20 patients with advanced soft tissue sarcomas at the maximum tolerated dose (MTD). The Phase I dose-escalation portion of the study assessed 25 patients with advanced solid tumors across four cohorts of increasing doses and found the MTD to be the highest tested dose level of 1000 mg/m2 intravenously-administered belinostat combined with 75 mg/m2 doxorubicin.

Common drug-related events included fatigue (95%), nausea (76%) and alopecia, or hair loss (63%), and one dose-limiting toxicity of Grade 3 rash was observed. Dose-normalized area under the curve and maximum concentration appeared relatively consistent across the different cohorts, indicating that belinostat exhibited linear pharmacokinetics across the dose range, and that doxorubicin had no effect on belinostat exposure. Two patients receiving the MTD exhibited partial responses, for a response rate of 8% (95% CI).

The Phase II portion, which assessed efficacy of the combination at MTD in 20 patients with soft tissue sarcomas including four patients from the Phase I portion, demonstrated two patient responses, 9 patients with stable disease and a response rate of 13% (95% CI). Of the two responses, one patient had a partial response at cycle 4 of treatment and the second patient had a complete response at cycle 2. These two responses resulted in stopping of the trial after enrolling 20 patients, meeting a pre-determined stopping rule that the Phase II trial would be stopped if no more than 2 responses (complete or partial) were seen among the 20 patients within the first two treatment cycles.

* On April 9, 2015, Onxeo announced that the phase I/II clinical trial of belinostat in combination with doxorubicin (PXD101-CLN-14) in patients with soft tissue sarcoma (STS) was accepted for presentation in the Poster Discussion Session at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO), taking place in Chicago, USA from May 29 to June 2, 2015. The PXD101-CLN-14 study was an open-label, multicenter, dose-escalation phase I/II to evaluate the safety and efficacy of the combination of belinostat with doxorubicin in patients with advanced solid tumors (the phase I part of the study) and STS (the phase II part of the study). The trial demonstrated that belinostat in combination with doxorubicin has an acceptable safety profile, allowing the combination of belinostat at the dose of 1000 mg/m2 on days 1-5 with 75 mg/m2 doxorubicin on day 5 in a three-week schedule. Signals of efficacy in STS patients were also demonstrated, in this highly severe disease.

In July 2014, belinostat (Beleodaq®) was granted accelerated approval in the USA by the FDA for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) in 2nd-line treatment after failure of standard chemotherapy. A phase III trial is planned to be initiated in H1 2016 to expand the indication from 2nd to 1st line of treatment of PTCL in collaboration with Onxeo’s US partner, Spectrum Pharmaceutical. Beyond PTCL, belinostat’s profile, supported by clinical data, advocates for its development in new promising orphan oncology indications. The company is currently reviewing potential indications in order to define the optimal development plan for belinostat.