China’s regulatory agency has approved the start of a Phase 3 clinical trial testing ATG-010 (selinexor), in combination with Velcade (bortezomib) and dexamethasone, in multiple myeloma patients after one to three prior lines of treatment.
The trial will include about 150 patients in China with relapsed of refractory multiple myeloma, and randomly assign them to the triple combination or to standard treatment with Velcade plus dexamethasone, and serving as a control group.
Findings from a global trial with a similar design — the BOSTON Phase 3 trial (NCT03110562) — supported ATG-010’s approval in the U.S., where it is marketed under the brand name Xpovio by Karyopharm Therapeutics.
“This planned Phase 3 trial, which is the registrational study based on BOSTON, is going to validate the [triple combination] regimen’s efficacy and safety in Chinese population,” Jay Mei, MD, PhD, founder, chairman and CEO of Antengene, said in a press release.
Under a collaboration agreement with Karyopharm, Antengene owns the rights to develop and commercialize Xpovio across multiple regions, including mainland China, Macau, Hong Kong, Australia, New Zealand, South Korea, Taiwan, and other Asian countries.
The company recently filed applications with health authorities in Singapore and Australia requesting the approval of Xpovio’s triple combination for myeloma patients who received at least one line of therapy. These requests were also based on BOSTON’s findings.
Xpovio is a first-in-class oral inhibitor of the XPO1 protein, a nuclear transporter that is produced in greater amounts by cancer cells to escape the action of tumor suppressor proteins. By preventing the exit of tumor suppressors from the cell nucleus, it can lead to cancer cell death.
BOSTON included a total of 402 adults, previously treated with one to three prior lines of therapy. All were randomly assigned to Xpovio, in combination with Velcade and dexamethasone, or to standard treatment with Velcade plus dexamethasone.
Compared with standard treatment, the Xpovio combination significantly extended the time patients lived without signs of disease progression, from a median of 9.5 months to 13.9 months — meeting the trial’s primary goal.
This 30% reduction in the risk of disease worsening or death was accompanied by additional benefits in patient outcomes. Those treated with Xpovio had better responses to treatment (76.4% vs. 62.3%), more complete responses (no signs of cancer; 17% vs. 10%), and experienced more durable responses (20.3 months vs. 12.9 months).
Xpovio also was linked to improvements in overall survival and to lower rates (21.0% vs. 34.3%) of severe peripheral neuropathy, or damage to the nerves controlling sensation and movement.
“The result of the BOSTON study has demonstrated that the [Xpovio] regimen reduced the risk of disease progression or death with lower doses of bortezomib and dexamethasone in the triplet combination when compared to the standard … regimen,” Mei said.
While BOSTON enrolled patients at 157 sites across 21 countries, the trial was mostly conducted in Europe and North America. The upcoming clinical trial, approved by China’s National Medical Products Administration, is designed to confirm BOSTON’s benefits in Chinese patients.
In addition to this Phase 3 trial, Antengene is also sponsoring two additional Phase 2 studies in China, testing ATG-010 in relapsed or refractory myeloma patients, and in relapsed or refractory diffuse large B-cell lymphoma.
The myeloma open-label trial, dubbed MARCH (NCT03944057), is recruiting 82 patients whose cancer failed to respond to at least one proteasome inhibitor and one immunomodulatory agent. Those enrolled will receive a combination of Xpovio plus low-dose dexamethasome. More information and contacts can be found here.
This combination is approved in the U.S. for adults with relapsed or refractory multiple myeloma who received at least four prior therapies and failed to respond to treatment with at least two proteasome inhibitors, two immunomodulatory agents, and a CD38 inhibitor.
A branch of the European Medicines Agency has also recommended the conditional approval of this combination for a similar indication.
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