Sonrotoclax Combination for Relapsed/Refractory AML

Acute myeloid leukemia (AML) patients may encounter more challenges in finding a long-term therapy. Although most people respond to their first line of treatment, more than half experience relapse. In relapsed or refractory (R/R) AML, there is no universally accepted treatment standard beyond enrolling in clinical trials.

Current treatment options fall short 

For people with R/R AML, standard chemotherapy produces complete response (CR) rates between 40% and 65%. However, the average survival is typically less than 12 months. These regimens are often difficult to tolerate due to low blood counts and an increased risk of infection.

More recent combinations like venetoclax (Venclexta, AbbVie) with hypomethylating agents (HMAs) such as azacitidine or decitabine have improved survival in newly diagnosed patients who are not candidates for intensive chemotherapy. In the relapsed setting, though, their effectiveness declines. Response rates drop to about 33% and median survival is just under 7 months.

Researchers have tested triple therapies that add drugs like aclarubicin or homoharringtonine to venetoclax and hypomethylating agents (HMAs). Some small studies report response rates above 70%. Still, there is an urgent need for more effective and better-tolerated therapies for R/R AML.

How Sonrotoclax works and why it is different

Sonrotoclax is a next-generation medication that blocks a protein called BCL2, which helps leukemia cells avoid cell death. It is designed to be more potent and selective than venetoclax. Because venetoclax may not work in some patients, sonrotoclax could offer another path forward.

A new clinical trial is evaluating sonrotoclax in combination with azacitidine (Vidaza, BMS) and a chemotherapy mix known as HAG. The HAG regimen includes homoharringtonine, cytarabine, and G-CSF, a growth factor that supports white blood cell production. This regimen is widely used in Asia and has shown favorable safety results.

See the latest results of an ongoing study for R/R AML

The results ongoing phase II trial are based on the participation of 27 adults with AML between the ages of 18 and 75 who met certain eligibility criteria based on health status and organ function.

The study is structured in two parts:

• Safety run-in phase: The first 6 patients received sonrotoclax along with azacitidine and the HAG regimen over a 28-day cycle. Sonrotoclax is given in increasing doses over four days, up to a target of 160 mg daily. If no more than one patient experiences side effects that can be controlled with side effects?, the study moves forward with that dose. If more than one experiences serious side effects, the dose may be lowered.
• Treatment phase: All patients then receive the selected dose for up to two 28-day cycles. If patients do not reach a composite complete response (CRc), they are considered to have not responded and will be offered other treatment options and followed for long-term outcomes. Those who do respond may proceed to a stem cell transplant at their doctor’s discretion.

Some participants may continue with additional therapy cycles. These include consolidation treatment using sonrotoclax and HAG, or maintenance treatment using sonrotoclax and azacitidine, depending on their condition and transplant plans.

The study goals

The primary goal is to find out how many patients are alive one year after starting treatment. Secondary goals include:

• Complete response rate at the end of induction
• The number of patients who achieve minimal residual disease (MRD) negativity
• Duration of response
• Relapse-free and event-free survival
• Overall safety of the treatment combination

If treatment choices feel limited, especially if earlier therapies have stopped working. Studies like this one provide new options for more effective and targeted options.

Sonrotoclax may offer a more powerful way to block leukemia survival pathways, especially in patients who have already tried venetoclax. While this research is still in early stages, the results could shape future treatment strategies for R/R AML.

Stay tuned for more treatment advances updates with the HealthTree News site and visit the Clinical Trial Finder to explore more ongoing trials. 

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Source: 

• THE SAFETY AND EFFICACY OF SONROTOCLAX COMBINED WITH AZACITIDINE (AZA) AND HAG IN PATIENTS (PTS) WITH REFRACTORY/ RELAPSED (R/R) ACUTE MYELOID LEUKEMIA (AML): A PHASE II STUDY