In an early clinical trial evaluating Kura Oncology’s anticancer drug, a patient died, causing the FDA to suspend the study, while an investigation aimed to find out whether the death was related to known complications of acute myeloid leukemia (AML) treatment.
this Partial clinical reservation The announcement on Wednesday means that patients currently participating in the study may continue to receive treatment with the trial drug KO-539. However, no new patients may be recruited to participate in the Phase 1b study until the partial suspension is lifted.
Kura in San Diego is developing KO-539 for the treatment of patients with AML with specific genetic characteristics. Kura drug is a small molecule that can block something called MenningAlthough menin is a tumor suppressor in the endocrine glands, the protein also plays a key role in the development of leukemia. The disease in these patients is driven by a gene rearrangement called KMT2A. In anti-money laundering, Cell Differentiation, The process of changing cells from one type to another is blocked. Therefore, immature cells accumulate. By targeting and inhibiting menin, Kura’s drugs aim to eliminate barriers to cell differentiation.
In the conference call, Kula CEO Troy Wilson said that the death may be related to differentiation syndrome. Complications are characterized by fever; weight gain; blood, pus, or other substances in the lungs that cause breathing difficulties; low blood pressure; and kidney failure. Wilson said the company found “fewer than a few” cases of differentiation syndrome in all patients treated with KO-539, which were treated with steroids.
Differentiation syndrome It is a known complication of menin inhibitor drugs and a wide range of leukemia treatments. Syndax Pharmaceuticals report Temporary data for the first stage It was pointed out in April that differentiation syndrome was one of the adverse events observed in the study, but no deaths were reported. Wilson said that distinction is the key to the design of Kura’s drug-distinguishing leukemia blasts, which is the abnormal white blood cell characteristic of AML. Wilson said that if the patient’s tumor burden is high, it will lead to faster or more severe differentiation, and problems will arise.
Wilson said that patients who died in the Kura clinical trial received the lower of the two doses evaluated in the clinical trial. These two doses were previously found to be safe and effective in the dose escalation part of the study. He added that patients have many complicating factors that may lead to death. The patient’s disease did not respond to the previous four-line treatment. Fluid has also been observed around the heart, and this problem is usually not related to differentiation syndrome.
According to Wilson, the FDA requires the company to review the safety database, especially looking for changes in blood cell counts related to the timing and dose of the drug. The agency also requested information about the company’s strategy to alleviate differentiation syndrome. Finally, Wilson said the FDA asked Kura to reiterate the rationale for choosing 200 mg and 600 mg doses for the study. He added that from a safety and tolerability perspective, the company believes that these two doses are suitable for testing.
Wilson described the FDA’s communication with the company as a “request for information.” He said that Kura will be able to quickly provide this information to the FDA, but cannot control the FDA’s response speed.
The patient’s cause of death may never be known. Wilson said that the patient’s family did not agree with the autopsy. He said that even if an autopsy is performed, it is difficult to determine the ultimate cause of death.
“Drug development is a business that overcomes setbacks,” Wilson said. “We still believe that we have the potential to develop a first-class neuronin inhibitor. As I mentioned, we have seen encouraging signs of activity. This is a very effective compound. We are learning how to use it. This is what you do with a new mechanism of action in a disease as challenging as AML.”
Public area picture From the National Cancer Institute
