Table of contents

• Overview of the Acalabrutinib trials
• Conditions being studied
• Who the trials include
• Trial phases and study designs
• Main endpoints being measured
• Key studies at a glance
• What these trial results mean for patients

Overview of the Acalabrutinib trials

The trial data show that Acalabrutinib is being studied in many interventional cancer trials, mostly in blood cancers.^[1] These studies look at Acalabrutinib alone and in combination with other treatments, and several compare it with placebo or other standard treatments.^[1]

The main goals across the trials are to measure how well treatment works, how long the disease stays under control, and how safe the treatment is in different patient groups.^[1]

Conditions being studied

Most trials focus on mantle cell lymphoma and chronic lymphocytic leukemia.^[1] Several studies also include small lymphocytic lymphoma, which is closely related to CLL, and some include diffuse large B-cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia.^[1]

Some studies are very specific and focus on special groups, such as previously untreated mantle cell lymphoma in Spain, high-risk CLL, or non-GCB diffuse large B-cell lymphoma.^[1]

Who the trials include

The trial populations are different from study to study.^[1] Some trials include people who have never been treated before, while others include patients whose disease has come back after treatment or did not respond to earlier therapy.^[1]

Several studies focus on older adults, including people over 70 or over 80 years old, and some include frail patients or patients with moderate to severe cardiac impairment.^[1] There are also trials for high-risk CLL, defined in the source data by factors such as 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV status.^[1]

Trial phases and study designs

The studies include Phase 1, Phase 2, Phase 3, and one Phase 4 trial.^[1] Phase 1 studies in the data mainly look at safety, dose finding, and tolerability, including one study that also measures dose-limiting toxicities and the maximum tolerated dose.^[1]

Phase 2 trials often look at response rates or progression-free survival in smaller groups, while Phase 3 trials compare Acalabrutinib-based treatment with other treatment strategies in larger groups.^[1] The Phase 4 study looks at tumor lysis syndrome risk during venetoclax treatment in previously untreated CLL and includes Acalabrutinib as one of the treatment options in the study design.^[1]

Many studies are randomized, which means patients are assigned by chance to different treatment groups.^[1] Some are open-label, meaning both the doctors and patients know which treatment is being given, while others are placebo-controlled or blinded.^[1]

Main endpoints being measured

The most common endpoint is progression-free survival (PFS), which means the time until the cancer gets worse or the patient dies from any cause.^[1] Another common endpoint is overall response rate (ORR), which measures how many patients have a partial or complete response to treatment.^[1]

Some trials measure complete response rates, MRD-negative complete response, or undetectable minimal residual disease in blood or bone marrow.^[1] Other studies focus on safety endpoints such as adverse events, serious adverse events, dose-limiting toxicities, treatment discontinuation, and cardiac or infection-related events.^[1]

Several studies also measure duration of response, overall survival, and specific investigator-assessed or independent review committee-assessed outcomes using criteria such as Lugano or iwCLL.^[1]

Key studies at a glance

Some of the largest Phase 3 studies compare Acalabrutinib-based treatment with other standard options in previously untreated CLL or SLL, including combinations with venetoclax, obinutuzumab, bendamustine, rituximab, or chemoimmunotherapy.^[1] These studies are designed to see whether Acalabrutinib can improve PFS or other response measures in first-line treatment.^[1]

In mantle cell lymphoma, trials study Acalabrutinib in newly diagnosed patients, older adults, and patients with relapsed or refractory disease, often in combination with R-CHOP, rituximab, bendamustine, or venetoclax.^[1] The goal is usually to improve response and keep the disease controlled for longer.^[1]

In more complex situations, such as CLL with cardiac impairment or very old or frail patients, the studies focus strongly on safety and tolerability as well as treatment effect.^[1]

What these trial results mean for patients

For patients, these trials show that Acalabrutinib is being tested in many different real-world situations, not just in one disease group.^[1] The studies try to find out which combinations work best, which patients may benefit most, and how to balance benefit with safety in older, frailer, or higher-risk groups.^[1]

Because the trials use different endpoints, a “good result” may mean different things in different studies, such as better response, longer disease control, or fewer serious safety problems.^[1] The trial data therefore give a broad picture of how Acalabrutinib is being tested across several blood cancers and patient groups.^[1]