Optimal Dose of Tasquinimod Found in First Phase of RRMM Trial

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by Marta Figueiredo |

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The optimal dosing of tasquinimod, Active Biotech’s experimental oral therapy for adults with relapsed or refractory multiple myeloma, has been determined in a Phase 1b/2a clinical trial.

Now, that dose and schedule will be tested, along with the standard oral combination treatment, in the trial’s second phase, the company said in a press release.

“We are pleased to have concluded the first part of this trial, confirming the previous safety profile of tasquinimod in patients with multiple myeloma and defining an optimal dose and schedule for tasquinimod in this patient population,” said Dan Vogl, MD, the trial’s principal investigator and the director of University of Pennsylvania’s Abramson Cancer Center.

The 10 patients included in the study’s first part “were heavily pre-treated, with a median of 8 prior lines of therapy,” Vogl said.

Based on the observed favorable safety data, and early, promising signs of anti-myeloma activity in these patients, the trial will now move into its next part, according to Active. The therapy will be tested together with the standard combination treatment — known as the IRd combo — that includes Ninlaro (ixazomib), Revlimid (lenalidomide), and dexamethasone, a corticosteroid.

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“Our preclinical laboratory models suggest that this combination strategy may be a particularly effective way to utilize tasquinimod in myeloma therapy,” Vogl said.

Tasquinimod is an orally available small molecule that works by targeting myeloid-derived suppressor cells (MDSCs), a type of immune cell that plays a key role in myeloma progression.

MDSCs not only prevent the recruitment and activation of tumor-killing immune cells, but also promote the formation of new tumor blood vessels that are essential for their growth and spread to distant parts of the body (metastasis).

As such, tasquinimod is thought to promote anti-tumor immune activity, and slow tumor growth and spread.

In preclinical models of multiple myeloma, the therapy showed potent anti-tumor effects, both alone and in combination with immunomodulatory treatments (IMiDs), such as Revlimid, and proteasome inhibitors (PIs), like Ninlaro.

The Phase 1b/2a trial (NCT04405167), launched in August 2020, was designed to establish the best dose and schedule for tasquinimod, both as a single therapy and together with the standard IRd combo Up to 34 adults with relapsed or refractory multiple myeloma are being recruited at the study’s single site, the Abramson Cancer Center, in Philadelphia.

Preliminary toxicity and the effectiveness of both regimens are among the trial’s goals.

Notably, eight of the 10 patients involved in the first part of the study, assessing the therapy alone, had failed to respond to IMiDs, PIs, and anti-CD38 antibodies. The optimal dose established in this part was 1 mg per day, which is similar to that used in previous tasquinimod studies.

“While none of the patients formally achieved a partial response, two patients with progressive myeloma at study entry achieved significant periods of stable disease on single-agent tasquinimod therapy,” Vogl said.

This preliminary efficacy data suggest the therapy has “anti-myeloma activity in patients with advanced disease that is resistant to established therapies,” supporting advancement into the combination part of the study, Vogl added.

The best dose and schedule of tasquinimod, taken together with the IRd combo, will now be determined among a set of participants. Once established, that dose will be further tested in an additional group of patients.

“We are enthusiastic to have reached this milestone and … we look forward to the continuation of the study,” said Helén Tuvesson, PhD, Active Biotech’s CEO.

“The use of tasquinimod, as a novel class of treatment for multiple myeloma, in combination with treatments used for earlier stage patients, is aligned with our current understanding of the mechanism of action of tasquinimod in these patients,” Tuvesson added.

Tasquinimod has been granted orphan drug designation in the U.S. for the treatment of multiple myeloma. That designation is meant to accelerate the therapy’s development and review by providing regulatory support and financial incentives, most notably a seven-year period of market exclusivity if the medication is approved.

The treatment was previously evaluated as a potential therapy for prostate cancer, with a Phase 3 clinical trial showing its superiority over a placebo in prolonging the time patients lived without signs of disease progression. However, the therapy was not associated with improved overall survival, prompting the discontinuation of that clinical program. The therapy’s tolerability is well-characterized based on these previous trials.

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