Sometimes, clinical trials do not go the exact way that is expected. According to Targeted Oncology, this is what happened in a Phase 1b clinical trial evaluating RVU120 for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). During the course of the trial, one patient died, causing safety concerns. Although the FDA placed a partial clinical hold on the trial to introduce new safety protocols, that clinical hold has now been lifted.

RVU120

According to an earlier news release from January 2021, drug developer Ryvu Therapeutics (“Ryvu”) describes RVU120 as:

a highly selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. RVU120…reduced tumor burden to the level undetectable in the peripheral blood, decreased splenomegaly and resulted in partial bone marrow recovery at well tolerated doses.

Thus far, RVU120 received Orphan Drug designation from the FDA.

Within this particular clinical trial, researchers were evaluating RVU120 for patients with AML or MDS. During the trial, patients were divided into 4 cohorts. They received anywhere from 10-75mg RVU120. The primary trial endpoint was to determine the maximum-tolerated dose and recommended Phase 2 trial dose. Median patient age was 74. Previously, patients had been treated for a mean of 3 times. Findings, presented at the 2021 European Hematology Association Congress, included:

• Despite the patient death, neither the death nor any serious adverse reactions (sepsis, urinary tract infection, lung infection, neutropenia) were associated with RVU12. Thus, the treatment was relatively safe and well-tolerated.
• One patient who received 10mg achieved a stable disease state, while another receiving 50mg responded well to therapy.
• In the 4th cohort, one patient had persistent AML extramedullary skin leukemia. Despite prior venetoclax treatment, his condition progressed. While on RVU120, this same patient achieved complete hematological recovery and saw symptom improvement.

Ultimately, the data was promising enough that the FDA believed RVU120 to show benefit for patients. During the partial clinical hold, enrolled patients were still treated. Now, with newly amended protocols and increased monitoring and laboratory testing, Ryvu may continue enrolling patients.

Myelodysplastic Syndromes (MDS)

Doctors are not sure exactly what causes myelodysplastic syndromes (MDS), which are progressive conditions which prevent bone marrow from producing enough platelets, as well as red and white blood cells. In patients with MDS, these cells are immature and never leave the bone marrow. Some doctors believe genetics, radiation, and chemical exposure can all play a role in MDS. Typically, MDS occurs in patients ages 60+. It often affects males more than females. In around half of all diagnoses, MDS progresses to become acute myeloid leukemia (AML). Although patients may be asymptomatic at first, when symptoms appear, these include:

• Anemia (low red blood cell count)
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Frequent infections
• Fatigue and lethargy
• Chest pain
• Easy bruising and bleeding
• Shortness of breath
• Abnormally pale skin
• Heart palpitations