Ibrutinib Displays Efficacy in Two Separate Clinical Trials

Pharmacyclics and Janssen R&D announced the results of two separate Phase 2 studies suggesting that ibrutinib, an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor, showed efficacy when used as a monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL). Ibrutinib was designed to specifically target and selectively inhibit an enzyme called BTK, a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel — regulation of apoptosis, cell adhesion and cell migration and homing.

The MCL study is a Phase 2 multicenter, open-label, study with 111 patients with relapsed/refractory MCL treated with ibrutinib and had received a median of three prior therapies. Patients were divided into two cohorts based on prior bortezomib exposure to either bortezomib-naive (n=63) or bortezomib-exposed (n=48). Both groups received 560mg of ibrutinib orally, once a day until disease progression or no longer tolerated by the patient. The primary endpoint of the study was ORR.

Among patients with relapsed/refractory MCL an overall response rate (ORR) of 68%, including a complete response (CR) of 21% where all signs of cancer were gone, and a partial response (PR) of 47% were observed.

The DLBCL study is a Phase 2 multicenter, open-label, study in which 70 patients with relapsed/refractory DLBCL with a median of three prior therapies were enrolled. All patients underwent gene expression profiling to determine which DLBCL subtype they had. Investigators examined whether ibrutinib would be more active in the Activated B-cell-like (ABC) subtype of DLBCL compared to the Germinal Center B-cell-like (GCB) subtype. The ABC subtype of DLBCL is dependent on the B-cell antigen receptor (BCR) pathway, of which BTK is a key element. All patients received ibrutinib 560mg orally, once a day, until disease progression or no longer tolerated by the patient. The primary objective of the study was to assess ORR categorized by subtype.

Results of this study show that patients with the ABC subtype showed a preferential response to ibrutinib monotherapy compared to those with the GCB subtype (ORR = 41% vs 5%, respectively, p=0.007, Fisher’s exact test). Median overall survival (OS) was 9.7 months for the ABC subtype, compared to 3.35 months for the GCB subtype.

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