Phase 1/2 Trial of Tinostamustine to Treat Blood Cancers Opens 2nd Stage

The expansion stage of a Phase 1/2 trial testing tinostamustine in relapsed or refractory types of lymphoma and other blood cancers has enrolled a first patient.

The study (NCT02576496) is currently enrolling up to 65 patients in the U.S. and Europe with advanced multiple myeloma, Hodgkin’s lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or T-cell prolymphocytic leukemia. More information on trial locations and contacts can be found here.

Tinostamustine (EDO-S101) is a blocker of the enzyme alkylating deacetylase, designed to have potent toxic effects against cancer cells by integrating multiple modes of action. Preclinical studies found that tinostamustine improves access to DNA strands within cancer cells, both by breaking them and by counteracting the cells’ mechanisms to repair this damage.

The therapy is being developed by Imbrium Therapeutics, a subsidiary of Purdue Pharma, in collaboration with Mundipharma EDO for both blood cancers and solid tumors.

After a dose escalation stage established tolerability, the expansion phase aims to assess tinostamustine’s overall response rate, duration of response, and safety. Each cancer type will be run independently. The trial’s results will be presented at upcoming medical meetings.

“We are excited to see the first patient enrolled in the tinostamustine expansion study in patients with hematologic malignancies,” John Renger, PhD, Imbrium’s vice president, Head of Research & Development and Regulatory Affairs, said in a press release.

Paul Medeiros, Imbrium’s president, added that “the initiation of the expansion arms of this Phase 1/2 trial is a significant step for our work in oncology.”

“We look forward to continue building on the foundation of safety data,” Medeiros added, “as we advance the development of tinostamustine as a potential therapy for people with limited treatment options.”

Preclinical results of tinostamustine as a stand-alone therapy have shown slowed disease progression in myeloid and lymphoid malignancies, and in solid tumors. According to Mundipharma, the therapy also increased the response seen with Velcade (bortezomib, by Takeda Oncology) and dexamethasone, suggesting improved efficacy and duration of effects.

Tinostamustine is also being assessed in a Phase 1/2 trial in multiple myeloma (NCT03687125), exploring a conditioning regimen with this therapy, followed by autologous stem cell transplant. Another Phase 1/2 study (NCT03345485) is testing tinostamustine’s tolerability and response rates in patients with solid tumors. Also, an ongoing Phase 1 trial (NCT03452930) is evaluating the safety and highest dose tolerable of tinostamustine given with or after radiation therapy to patients with glioblastoma, a type of brain cancer.

Patient enrollment is ongoing in these three trials. For more information about contacts and study locations, please click on the trials’ identifying NCT number.

Besides tinostamustine, Imbrium’s oncology portfolio includes etoposide toniribate, a treatment candidate for biliary tract cancer. Through its partnership with Mundipharma, Imbrium is currently testing four investigational therapies across 14 different cancer types.