Medically reviewed by Dr. Brian Koffman
The Bottom Line:
A new clinical trial is recruiting patients with relapsed / refractory B-cell cancers to test the safety of a new experimental MALT1 inhibitor. Because MALT1 is downstream from BTK and PLCG2 in the B cell receptor pathway, this MALT1 inhibitor may be useful for patients with BTK resistance mutations or PLCG2 mutations.
Who Performed the Research and Where Was it Presented:
Dr. Meghan Thompson from Memorial Sloan Kettering Cancer Center and colleagues presented the study design at the American Society for Hematology (ASH) Annual Meeting 2023.
Background:
Targeted therapy is a type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread. Targeted therapies have revolutionized the treatment of CLL / SLL, and thus far, we have two main classes of drugs that are used. Bruton tyrosine kinase (BTK) inhibitors turn off BTK, a key protein in the B cell receptor (BCR) pathway critical for B cell proliferation. BCL-2 inhibitors block the action of the BCL-2 protein, a survival protein overexpressed in CLL, and cause the death of CLL cells. While BTK inhibitors and BCL-2 inhibitors are very effective for treating CLL, patients can develop resistance to both drug classes over time. Thus, it is important to continue researching new therapies that use different mechanisms of action.
MALT1 is a protein in the BCR pathway that is downstream of BTK and PLCG2. So, if a patient has developed resistance mutations in BTK or PLCG2, a drug that blocks a protein further down the BCR pathways, such as MALT1, could be an alternative way of inhibiting the BCR pathway. However, no approved drugs can be expected to work well with patients who have a PLCG2 mutation.
Methods and Participants:
- Dr. Thompson and colleagues are currently recruiting patients for a first-in-human phase 1 clinical trial to test the safety of ABBV-525, a new MALT1 inhibitor, for patients with relapsed / refractory B-cell cancers.
- The primary objectives are to evaluate ABBV-525’s safety, tolerability, and pharmacokinetics and to determine the recommended phase 2 dose.
- Researchers will also evaluate preliminary efficacy in a subset of patients.
- Researchers plan to enroll 150 patients at sites in the USA, Australia, Belgium, France, Germany, Israel, Spain, and the UK.
- The study will include patients with:
- Various relapsed / refractory mature B-cell lymphomas
- Relapsed / refractory CLL
- Non-germinal center B-cell diffuse large B-cell lymphoma (non-GCB DLBCL)
- If you are interested in participating, more information can be found here: Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets.
Conclusion:
We need more options for patients than the two main classes of targeted therapies we have today. This is not a drug that tries to improve on existing options, as valuable as that can be. It is a drug that exploits a whole new target that holds promise if it proves effective and safe in trials like this.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: A First-in-Human Phase 1 Study of ABBV-525, a Small-Molecule MALT1 Inhibitor, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Take care of yourself first.
Ann Liu, PhD
