PT-112 Shows Promise for Heavily Treated Myeloma Patients

Phosplatin Therapeutics‘ investigational medication PT-112 showed promising efficacy and safety data in an early clinical trial of heavily-pretreated people with relapsed or refractory multiple myeloma.

The findings were shared in a presentation, “A Phase I Dose Escalation Study of PT-112 in Patients with Relapsed or Refractory Multiple Myeloma,” at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, which took place virtually in December.

Within the body, cell death is a common phenomenon — individual cells die as part of a variety of normal, healthy biological processes. At other times, cells die because of disease, like an infection.

Conceptually, cells die in two ways. Healthy cell death typically occurs in a fashion that is not immunogenic (it doesn’t prompt any activity from the immune system) but, sometimes, cells can undergo immunogenic cell death (ICD).

When a cell undergoes ICD, it releases a number of immune-stimulating molecules as it dies. This can act as a signal to the immune system that something is wrong. For example, if a virus-infected cell undergoes ICD, it can alert the immune system that there is an infection that needs to be fought.

In addition to fighting infections, the immune system has the capacity to kill cancer cells, though tumors will often evolve mechanisms that lets them avoid the immune system’s attacks.

PT-112 is a small molecule that is designed to trigger ICD in cancer cells, which could prompt an immune response against the remaining cancer. Of note, PT-112 has a property known as osteotropism, meaning that the medication tends to reach its highest concentrations in certain areas of the bone. As such, it is a candidate for treating patients with cancers that originate in, or spread to, the bone. Multiple myeloma, which originates in the bone marrow, is one such cancer.

As a potential treatment for multiple myeloma, PT-112 has been designated an orphan drug in the U.S.

At ASH’s annual meeting, researchers from Phosplatin and other institutions presented data from a Phase 1/2a clinical trial (NCT03288480) that tested PT-112 in people with relapsed or refractory multiple myeloma.

In the trial, 24 people were given one of six dose levels of PT-112, ranging from 125 to 420 mg/m². The median age of participants was 72 years, and they were heavily pre-treated, having undergone a median of eight prior lines of therapy.

Nearly all (92%) participants were triple-class refractory, meaning their cancer failed to respond to at least three prior types of treatment. Most (79%) were penta-refractory (their cancer didn’t respond to at least five prior treatments).

The trial’s main goal was to determine the best dose of PT-112 for use in subsequent clinical testing, based on the therapy’s observed safety profile.

Based on the data, the trial’s safety committee determined 360 mg/m² as the optimal dose for subsequent testing. Among eight trial participants who were treated at or above this dose, four responded to therapy, and two had stable disease. Two of the responders were penta-refractory, and they lived without signs of disease worsening for 4.5 months.

The most common adverse events were thrombocytopenia (low platelet levels), neutropenia (low neutrophil levels), diarrhea, and nausea. One dose-limiting toxicity was reported: a case of severe neutropenia in a person treated at the highest dose level.

This was “an encouraging result in a dose escalation trial conducted in heavily refractory patients,” the researchers concluded. “PT-112 monotherapy [without additional treatments] was feasible and well tolerated in this heavily pre-treated, multi-refractory multiple myeloma population.”

They said that these findings support further clinical development of PT-112.