Karyopharm drug tested in ‘industry-first’ approach to brain cancer

The unusual phase 0/2 design starts with a preclinical phase in which Xpovio (selinexor) will be tested as part of several drug cocktails for glioblastoma – on a patient-by-patient basis – by scientists from the Ivy Brain Tumor Center in Phoenix, Arizona.

Selinexor – a first-in-class oral XPO1 inhibitor – will initially be given alongside various other new experimental drugs to see which combinations have the greatest potential in the study, described as an ‘industry-first approach’ to drug testing.

The tissue-based testing design can show if a combination is having an impact on a patient’s tumour in as little as seven days, allowing patients to quickly continue onto an advanced trial or switch to a different treatment, says Nader Sanai, a neurosurgical oncologist and director of the Ivy Centre.

Glioblastoma – the cancer that killed US Senators John McCain and Ted Kennedy – is one of the deadliest types of cancer with a median survival of just 14 months, and has proved to be one of the toughest challenges for drug developers.

According to the Ivy Centre, only five drugs have been approved for brain cancer patients in the US since 1982, while in the same timeframe more than 50 have been approved to treat lung cancer patients.

Xpovio is variously described as a selective inhibitor of nuclear export (SINE) or an ‘exportin’ inhibitor, forcing tumour suppressor proteins such as p53 and p27 to be retained and accumulate in the cell nucleus, resulting in cell death.

It was approved to treat multiple myeloma earlier this month – despite a call for a delay by an FDA advisory committee – and is also in mid- and late-stage testing in lymphoma as well as solid tumours such as liposarcoma and endometrial cancer.

It’s already in a phase 2 trial as a second-line monotherapy in relapsed or refractory glioblastoma patients.

Results in 30 subjects presented at the ASCO congress in June showed that the drug was able to achieve a 10% response rate – including one complete response and two partial responses.

While not impressive at first glance, that is around twice what has been achieved with other drugs and 19% of the group had progression-free survival of six months.

“Selinexor exploits a compelling target in glioblastoma patients, which is why we have selected it as the backbone of a new experimental drug cocktail,” says Sanai.

“Our scientific partnership with Karyopharm…will arrive at a new therapeutic strategy that can be accelerated into the clinic and patients in need.”