US-based Epizyme has begun its Phase II trial of tazemetostat for the treatment of adults with genetically defined tumours.
The company has also started enrolment in the Phase I dose escalation study in pediatric patients with the same tumour types.
The cancers being evaluated in these trials, INI1-negative tumors, certain SMARCA4-negative tumors and synovial sarcomas, are aggressive cancers that are poorly served by current treatments.
The first sites for adult enrolment to be activated are Northwestern University, MD Anderson Cancer Center, and Cincinnati Children’s Hospital.
The Dana Farber Cancer Institute and Cincinnati Children’s Hospital have been activated for pediatric enrolment.
The company plans to add sites in the US, Canada, Europe and Australia over the next few months.
Dana-Farber Cancer Institute Center for Sarcoma and Bone Oncology director Harvard Medical School professor of Medicine George Demetri said: "Life-threatening rare tumors such as rhabdoid tumors, epithelioid sarcomas and synovial sarcomas affect children and young adults who are in need of novel effective therapies, since the standard approaches are only marginally useful.
"We are enthusiastic about evaluating tazemetostat in our patients with these forms of sarcomas, since the molecular mechanism is so compelling, especially with the recent identification of mutations in INI1 or SMARCA4 as genetic drivers for these cancers."
A total of 90 patients will be split into three groups in the adult Phase II multicentre trial.
The first group will include patients with malignant rhabdoid tumour, rhabdoid tumour of the kidney, and atypical teratoid rhabdoid tumour, all of which are characterised by INI1 or SMARCA4-negativity.
The second group will be comprised of patients with non-rhabdoid, INI1-negative tumours, including epithelial sarcoma, epithelioid malignant peripheral nerve sheath tumour, extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma, and renal medullary carcinoma.
The trial’s third group will include patients with synovial sarcoma, in which INI1 is deregulated by a reciprocal translocation between chromosome 18 and the X chromosome.
In these groups, patients will be dosed with 800mg tablets twice a day.
The primary endpoint of the trial is overall response rate (ORR) for patients with INI1-negative tumours, and progression-free survival (PFS) for patients with synovial sarcoma.
The trial’s secondary endpoints include duration of response, overall survival (OS), and PFS for patients with INI1-negative tumours, as well as safety and pharmacokinetics (PK).
Around 40 patients will be enroled in the pediatric Phase I multicentre study in a dose escalation design, followed by dose expansion, with an oral suspension of tazemetostat.
INI1-negative or certain SMARCA4-negative tumours are characterised as aggressive cancers, with few to no approved treatments.