Cerdulatinib is an oral, dual Syk-JAK inhibitor with a unique mechanism of action.

It inhibits two key signaling pathways that promote cancer cell growth in certain haematologic malignancies: the B-cell receptor pathway via Syk and key cytokine receptors via JAK.

Preclinical data suggested that cerdulatinib may have anti-tumour activity in patients who did not adequately respond to, or relapsed on, other treatments due to defined mutations.

The current study is evaluating the safety and efficacy of cerdulatinib in patients with certain types of non-Hodgkin Lymphoma.

Up to 40 patients each will be enrolled in cohorts including patients with relapsed/refractory chronic lymphocytic leukaemia (CLL), and indolent lymphomas such as follicular lymphoma (FL) and peripheral T cell lymphoma (PTCL).

The interim results presented at EHA 2017 demonstrated evidence of differentiated clinical activity in patients with relapsed/refractory B-cell malignancies.

To date, overall response rates are as follows:

• 12 out of 18 (67%) partial responses (PRs) in patients with r/r CLL/SLL
• 5 out of 9 (56%) PRs in patients with r/r FL
• 1 out of 7 (14%) PRs in patients with r/r iNHL (marginal zone lymphoma and Waldenstrom macroglobulinemia)
• A complete response (CR) was seen in the first r/r peripheral T cell lymphoma (PTCL) patient evaluated in the study
• PRs have been seen in heavily pre-treated patients, including a patient with FL who relapsed on ibrutinib and a patient with SLL who relapsed on venetoclax, both of whom remain on drug after 10 months of therapy

Results also showed that cerdulatinib was generally well-tolerated in these heavily pre-treated patients (at target drug levels).

However, three patients at 35 mg BID achieved higher than expected drug concentrations and had severe adverse events including two grade 5 infections and one case of grade three pancreatitis.

The dose was subsequently reduced to 30 mg BID and a PK monitoring strategy was implemented.

This has resulted in an improved safety profile and more consistent PK, while still maintaining clinical activity.

Source: EHA 2017