Glioblastoma trial adds new drug in search for better treatments

A new arm of a clinical trial has begun testing Knoa Pharma‘s experimental therapy tinostamustine in people with glioblastoma, an aggressive form of glioma.

The Phase 2/3 trial, called the Glioblastoma Adaptive Global Innovative Learning Environment, or GBM AGILE (NCT03970447), is sponsored by the Global Coalition for Adaptive Research (GCAR), a nonprofit dedicated to modernizing clinical trial designs to speed the development of treatments and cures for serious diseases.

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Adaptive trial tests multiple therapies

Many traditional clinical trials test one experimental therapy at a time, but the GBM AGILE study uses a novel design in which multiple experimental agents from different developers are tested against a shared control group. The trial is designed so that findings may potentially support applications seeking approval for any of the experimental therapies if proven effective. The trial is actively recruiting participants at sites in the U.S., Canada, Australia, France, Germany, and Switzerland.

“By leveraging an adaptive platform design, we can assess promising treatments more rapidly than traditional clinical trials and make smarter, data-driven decisions sooner. GBM AGILE’s ability to evaluate therapies in newly diagnosed patients while simultaneously identifying signals in recurrent disease provides a powerful opportunity to accelerate the development of potential new options for patients with glioblastoma,” Meredith Buxton, PhD, CEO and president of the GCAR, said in a press release.

Tinostamustine is an investigational anticancer therapy designed to kill cancer cells through two complementary biochemical mechanisms, known as bifunctional alkylating activity and pan-histone deacetylase inhibition. Broadly, these mechanisms are intended to work together to kill cancer cells, including by damaging DNA and disrupting processes that help cancer cells survive. Because many cancer cells divide rapidly and must copy their DNA, this type of damage can be lethal to them.

According to Knoa, a public health-focused pharmaceutical company owned by a not-for-profit foundation, earlier clinical research in people with MGMT promoter-unmethylated glioblastoma found tinostamustine was tolerable at certain doses, with manageable side effects. The earlier Phase 1 trial wasn’t designed to test the therapy’s effectiveness, but exploratory analyses “showed encouraging signals of clinical activity,” the company said.

Drug tested after standard treatment

The GBM AGILE study is now testing tinostamustine as an adjuvant therapy in people with newly diagnosed glioblastoma following standard treatment, such as surgery, chemotherapy, and radiation. The trial is also testing tinostamustine in a limited cohort of patients with recurrent glioblastoma, meaning the cancer has come back after initial treatment.

“GBM AGILE was designed to accelerate the development of treatment options, which is why we’re honored to work with GCAR to determine whether tinostamustine could provide meaningful benefit to patients,” said Julie Ducharme, PhD, vice president and chief scientific officer at Knoa. “Encouraging findings from prior clinical studies support continued investigation.”

The first newly diagnosed patient was randomized to the tinostamustine arm of GBM AGILE in early April, and the first recurrent patient has been dosed with the experimental therapy.

“Glioblastoma patient outcomes have seen minimal improvement over the past several decades. The first patients randomized and dosed with tinostamustine marks an important milestone as we work to advance new treatment options and bring new hope to patients,” Buxton said.