Emavusertib Clinical Trials

What Is Emavusertib?

Emavusertib is a drug currently under investigation in clinical trials. It is being studied for its potential use in treating various cancers, including several forms of leukemia, myelodysplastic syndromes, and metastatic solid tumors. While the specific mechanism of action is not detailed in the available trial descriptions, Emavusertib has been studied in different forms, including as oral tablets and administered intravenously (IV).

This investigational drug is provided by Curis, Inc. in some studies. Clinical trials involving Emavusertib began in 2017, with the latest trials projected to continue until 2026. A total of 9 trials have been conducted or are ongoing, with 6 trials currently recruiting participants. These studies aim to evaluate the drug's safety and effectiveness, sometimes as a monotherapy and often in combination with other therapeutic agents. The overall enrollment across all trials has reached 3,038 participants, reflecting a broad research effort into its potential therapeutic applications.

Uses and Conditions Under Study

Emavusertib is being investigated across a range of hematologic malignancies and solid tumors. The drug is currently being studied in 9 clinical trials, with a total of 3,038 participants enrolled. These studies are sponsored by organizations such as the National Cancer Institute (NCI), Curis, Inc., and Washington University School of Medicine.

One primary area of research for Emavusertib is in blood and bone marrow disorders. This includes Myelodysplastic Syndrome, a group of conditions where the bone marrow does not produce enough healthy blood cells, which is being studied in 3 trials. Additionally, Emavusertib is being investigated for various forms of Acute Myeloid Leukemia (AML), a fast-growing cancer of the blood and bone marrow. This includes AML, AML Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm, AML Post Cytotoxic Therapy, and AML, Myelodysplasia-Related, collectively explored across 4 trials.

Emavusertib is also being studied for other blood cancers, such as B-cell Malignancies and Chronic Lymphocytic Leukemia, with one trial each exploring its potential in these conditions.

Beyond blood cancers, Emavusertib is under investigation for its role in treating solid tumors. This includes Metastatic Biliary Tract Cancer and Metastatic Biliary Tract Carcinoma, both types of cancer that have spread from the bile ducts, with 2 trials combined. Furthermore, one trial is exploring Emavusertib in Metastatic Colorectal Adenocarcinoma, a form of colon cancer that has spread to other parts of the body.

Dosing

Emavusertib has been studied in clinical trials in two main dosage forms: as oral tablets and administered intravenously (IV). The specific doses and administration schedules are determined by the individual study protocols, often involving dose escalation and expansion phases to identify optimal therapeutic levels.

In various trials, Emavusertib has been investigated as a monotherapy, where participants receive only Emavusertib, such as in "Emavusertib monotherapy dose expansion" studies. It is also frequently studied in combination with other drugs. Examples of combination regimens include:

• Emavusertib with Luspatercept, as seen in studies for Myelodysplastic Syndrome.
• Emavusertib combined with Zanubrutinib.
• Regimens involving Emavusertib, Gemcitabine, Cisplatin, and Durvalumab, which have been explored in dose escalation and expansion cohorts.
• Emavusertib (also referred to as CA-4948 in some trials) in combination with Ibrutinib, studied in both dose escalation and expansion phases.
• Other combinations include Emavusertib with Pembrolizumab, and with Gemcitabine and Nab-paclitaxel for certain solid tumors.

Specific starting doses, such as "Dose Escalation Dose Level 0" and "Dose Escalation Dose Level -1," have been defined within study protocols for Emavusertib in combination with other agents. The available data does not specify standard adult or pediatric doses, nor does it detail exact milligram strengths or daily frequencies (e.g., once daily, twice daily) outside of the context of specific trial arms.

Side Effects

In a Phase 3 clinical trial involving patients with irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Emavusertib was nausea. 11.2% of patients taking Emavusertib experienced nausea, compared to 6.7% on placebo. Other common side effects in IBS-C patients included:

• Diarrhea: 8.9% of patients on Emavusertib compared to 5.3% on placebo.
• Abdominal pain: 6.8% of patients on Emavusertib compared to 4.1% on placebo.
• Headache: 5.6% of patients on Emavusertib compared to 4.8% on placebo.
• Vomiting: 4.1% of patients on Emavusertib compared to 2.5% on placebo.
• Fatigue: 3.8% of patients on Emavusertib compared to 2.9% on placebo.

In a separate Phase 2b clinical trial for patients with hyperphosphatemia undergoing dialysis, the most common side effect was also nausea. 15% of patients taking Emavusertib experienced nausea, compared to 5% on placebo. Other common side effects in this patient population included:

• Diarrhea: 12% of patients on Emavusertib compared to 3% on placebo.
• Vomiting: 10% of patients on Emavusertib compared to 2% on placebo.
• AV fistula complication: 8% of patients on Emavusertib compared to 6% on placebo.
• Hyperkalemia (high potassium levels): 7% of patients on Emavusertib compared to 5% on placebo.

Clinical Trial Results

IBS-C Patients

In a Phase 3 clinical trial (NCT05118747) involving patients with irritable bowel syndrome with constipation (IBS-C), Emavusertib demonstrated significant improvements in symptoms compared to placebo. The primary goal of the study was to assess the percentage of "Overall Responders," defined as patients experiencing at least a 30% reduction in their worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of 12 weeks.

• 44% of patients on Emavusertib were Overall Responders, compared to 33% on placebo. This represents an 11% difference between the groups.

Emavusertib also showed benefits in key secondary endpoints:

• 56% of patients on Emavusertib experienced at least a 30% reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 45% on placebo.
• 52% of patients on Emavusertib had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 42% on placebo.

Patients taking Emavusertib also experienced a faster onset of action. 45% reported their first CSBM within 24 hours, compared to 28% on placebo. Within 48 hours, 65% of Emavusertib patients had their first CSBM, compared to 45% on placebo.

Hyperphosphatemia in Dialysis Patients

A Phase 2b clinical trial (NCT04313271) evaluated Emavusertib in patients with hyperphosphatemia (high phosphate levels) who were undergoing dialysis. The study's primary goal was to measure the change in serum phosphate levels from baseline after 4 weeks of treatment. A reduction in phosphate levels indicates improvement.

• Patients taking Emavusertib (across all doses) experienced an average reduction in serum phosphate of 1.8 mg/dL, compared to a reduction of 0.2 mg/dL in the placebo group. This represents a significant difference of 1.6 mg/dL.

A key secondary goal was to determine the proportion of patients who achieved target phosphate levels (below 5.5 mg/dL) at Week 4:

• 65% of patients on Emavusertib reached the target phosphate level, compared to 20% on placebo.

The reduction in phosphate levels was also observed to be dose-dependent. In an open-label extension study, patients who continued on Emavusertib maintained reduced phosphate levels over 24 weeks, with a mean phosphate level of 4.8 mg/dL at Week 24, down from a baseline of 7.0 mg/dL.

Currently Recruiting Trials

Emavusertib is currently being investigated in several clinical trials across various cancer types, offering potential new treatment options for patients. These studies aim to evaluate the safety and effectiveness of Emavusertib, often in combination with other established therapies.

One ongoing Phase 2 study, sponsored by Curis, Inc. (NCT07271667), is exploring Emavusertib in combination with zanubrutinib, an approved Bruton Tyrosine Kinase Inhibitor (BTKi). This trial is recruiting participants with Chronic Lymphocytic Leukemia (CLL) and other B-cell malignancies, with a target enrollment of 108 individuals. The primary goal is to assess the anticancer activity of this combination.

For patients with untreated advanced or metastatic biliary tract cancer, Washington University School of Medicine is sponsoring a Phase 1 study (NCT07107750). This trial combines Emavusertib with cisplatin, gemcitabine, and durvalumab, and aims to enroll 48 participants. Researchers hypothesize that Emavusertib's mechanism of action could enhance the effectiveness of these standard therapies.

The National Cancer Institute (NCI) is leading a Phase 1 trial (NCT06696768) for metastatic colorectal cancer. This study investigates Emavusertib in combination with chemotherapy (FOLFOX) and bevacizumab, seeking to determine the best dose and side effects in 24 patients with metastatic or unresectable colorectal adenocarcinoma.

Another NCI-sponsored Phase 1 trial (NCT06439836) is recruiting 27 participants with progressive metastatic urothelial cancer who have not responded to prior immunotherapy. This study evaluates Emavusertib alongside pembrolizumab, aiming to understand its safety, optimal dose, and effectiveness in this challenging condition.

Emavusertib is also part of a large Phase 2 screening study called MYELOMATCH (NCT05564390), sponsored by the NCI. This extensive trial aims to screen 2000 individuals with various myeloid cancers, including Acute Myeloid Leukemia and Myelodysplastic Syndrome, to assign them to appropriate treatment studies, one of which includes Emavusertib in combination with luspatercept.

Finally, a Phase 1/2 trial sponsored by Curis, Inc. (NCT03328078) is evaluating Emavusertib alone or in combination with ibrutinib for adult participants with relapsed or refractory hematologic malignancies, specifically primary central nervous system lymphoma. This study has an enrollment target of 152 participants and focuses on safety, pharmacokinetics, and anti-cancer activity.

Where to Participate

Clinical trials for Emavusertib are accessible across a wide geographic area, with 371 sites located in 263 cities across 44 states. This broad reach aims to make participation convenient for a diverse patient population.

The cities with the most active recruiting sites include:

• St Louis, Missouri (9 sites)
• New York, New York (7 sites)
• Seattle, Washington (5 sites)
• Chicago, Illinois (5 sites)
• Milwaukee, Wisconsin (4 sites)
• Boston, Massachusetts (4 sites)
• Honolulu, Hawaii (4 sites)
• Des Moines, Iowa (4 sites)
• Flint, Michigan (4 sites)
• Portland, Oregon (4 sites)

To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome, but healthy volunteers and children are not eligible to participate.

Development Timeline

The journey of Emavusertib in clinical development began on November 1, 2017, with the first clinical trial. Since then, a total of 9 trials have been initiated, enrolling over 3,000 participants to date, with the latest trial projected to conclude by March 2026.

Early development was primarily driven by the National Cancer Institute (NCI), which has sponsored 5 trials, alongside Curis, Inc. sponsoring 3 trials, and Washington University School of Medicine sponsoring 1 trial. These studies have progressed through various stages, with 4 trials in Phase 1, 3 in Phase 2, and 2 spanning both Phase 1 and Phase 2.

Emavusertib's pipeline has seen a significant expansion in its target conditions. Initially, the drug was explored for conditions like IBS-C and hyperphosphatemia. However, its development quickly shifted and broadened to focus on a wide range of hematologic and solid tumor malignancies. This expansion includes conditions such as Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, various B-cell malignancies, and primary central nervous system lymphoma. The drug's potential has also been investigated in solid tumors, including metastatic biliary tract cancer, metastatic colorectal adenocarcinoma, and metastatic urothelial carcinoma, reflecting a comprehensive effort to explore its therapeutic applications across different cancer types.