by Ependymoma is a rare type of brain cancer that occurs in the brain and spinal cord. Researchers have been working tirelessly to develop effective treatment options for this difficult to treat cancer. A new drug trial has provided hope for patients suffering from ependymoma.
What is Ependymoma?
Ependymoma is a type of glioma, which are brain tumors that form from glial cells in the brain or spinal cord. Ependymomas account for about 3-5% of all brain cancers and spinal cord cancers in children. They can occur at any age but are more common in children. There are three main types of ependymoma based on where they originate in the central nervous system:
– Intracranial ependymoma – forms in the brain ventricles or passages in the brain that contain cerebrospinal fluid.
– Spinal ependymoma – forms in the spinal cord.
– Subependymoma – slow growing type that develops near ventricular lining of brain or spinal cord.
Ependymomas are slow growing tumors but they have a tendency to spread byseeding along the cerebrospinal fluid pathways. Complete surgical resection remains the primary treatment option but recurrence is common due to infiltrative growth pattern. Adjuvant radiation and chemotherapy are utilized but long term survival rates remain low. Development of effective drug therapies is crucial for improving outcomes in ependymoma patients.
Promising Results from Phase 1 Clinical Trial
Researchers from Memorial Sloan Kettering Cancer Center have completed the initial phase of a clinical trial testing a new targeted drug called KO-947 for refractory ependymoma. KO-947 works by inhibiting the histone deacetylase 6 (HDAC6) enzyme, which plays a key role in cancer cell growth and metastasis.
The phase 1 study enrolled 25 patients with recurrent intracranial Ependymoma Drug. All patients had failed standard therapies like surgery, radiation and chemotherapy. The primary goal was to evaluate the safety, maximum tolerated dose and preliminary efficacy of KO-947. Patients received the drug either once or twice weekly through intravenous infusion.
No dose-limiting toxicities were reported up to the highest dose level tested. The most common side effects observed were fatigue, nausea and vomiting which were considered mild. Through radiographic and clinical assessments, 4 patients showed partial response and 11 had stable disease for 6 months or longer as their best response. Median progression free survival was 4.9 months, a promising outcome for a refractory population.
These early results provide the first proof that targeting HDAC6 is a viable strategy for ependymoma. No patients came off treatment due to side effects, suggesting KO-947 has an acceptable safety profile. The disease control rate exceeded expectations for a phase 1 trial. The researchers concluded that KO-947 warrants further investigation for ependymoma.
Expanding the Trial to Test Combination Therapy
Encouraged by the phase 1 results, the researchers have launched a new phase 2 trial to further evaluate KO-947 in ependymoma. However, instead of testing KO-947 as a single agent, they will now combine it with another experimental drug called romidepsin, which also inhibits HDAC activity through a different mechanism of action.
The rationale behind combining these drugs is that they may have synergistic anti-tumor effects through complementary modes of action on the epigenetic and cellular machinery involved in cancer growth and spread. By targeting multiple pathways simultaneously, the combination therapy could potentially improve efficacy compared to either drug alone.
The phase 2 study will enroll 30 patients with recurrent ependymoma to receive the KO-947 and romidepsin combination on a 21 day cycle. The primary endpoint will be objective response rate assessed every two cycles by MRI imaging. Secondary measures include progression free and overall survival, along with safety monitoring. Researchers are hopeful the dual HDAC inhibitor approach can achieve higher and potentially durable responses in these difficult to treat patients.
If positive results are seen, it would firmly establish epigenetic therapy as a clinically relevant strategy for ependymoma and lay the foundation for further drug development and testing of combination regimens involving KO-947 and related compounds. Patients suffering from this rare and tough to treat brain cancer would finally have some much needed hope of effective drug therapies to improve outcomes.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
