The phase IIb UNITY-NHL clinical trial (NCT02793583) aims to determine whether the novel drug umbralisib (TGR-1202) could be used as monotherapy or in combination with other drugs to treat patients with relapsed/refractory non-Hodgkin lymphoma (NHL).
Patients with relapsed/refractory non-Hodgkin lymphoma (NHL) have limited options for treatment, and effective advanced stage therapies must be developed for many subtypes of the disease. In the search for solutions, investigators are turning to combination therapies. The phase IIb UNITY-NHL clinical trial (NCT02793583) aims to determine whether these needs can be addressed using the novel drug umbralisib (TGR-1202) as monotherapy or as part of a doublet or triplet. The doublet includes ublituximab (TG-1101), and the triplet includes ublituximab and bendamustine (Treanda).
Umbralisib’s unique mechanism of action makes it a good candidate for combinations and monotherapy. The orally available PI3Kδ inhibitor has demonstrated strong activity in numerous preclinical models and in primary cells from patients with hematologic malignancies, according to the drug’s developer, TG Therapeutics in New York, New York. PI3Kδ is strongly expressed in hematopoietic cells and believed to be important in the proliferation and survival of B-cell lymphocytes.1 Umbralisib stands out among PI3K inhibitors for its superior safety and tolerability.
Ublituximab, also developed by TG Therapeutics, is a monoclonal antibody that targets an epitope on the B-lymphocyte CD20 antigen. Anti-CD20 antibodies target and aid in the depletion of B-lymphocytes.2
The chemotherapy bendamustine is a bifunctional mechlorethamine derivative that has shown alkylator and antimetabolite activity. The exact mechanism of action is unknown, but the bifunctional covalent linkage can lead to cell death via several pathways, and the drug is active against both quiescent and dividing cells.3
The trial has 3 experimental arms: umbralisib oral daily dose used alone, combined with intravenous (IV) ublituximab, and combined with IV ublituximab and bendamustine. Overall response rate will be the primary outcome measure, with a time frame of 8 to 12 weeks for up to 2 years. The secondary outcome measure will be progression-free survival, assessed from the date of randomization until the first documented progression, through 2 years.4 Future cohorts will evaluate umbralisib and ublituximab for indolent lymphoma.
WHO IS ELIGIBLE?
The UNITY-NHL study is enrolling patients with 4 different subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL). Umbralisib is being tested as monotherapy in FL, SLL, and MZL, whereas the DLBCL subtype is being treated with doublet or triplet therapy. Each subtype has its own eligibility criteria. All participants must have relapsed/refractory NHL that has not responded to standard treatment.