NEW YORK—Biopharmaceutical company TG Therapeutics Inc. has had a busy couple of months presenting data at a trio of conferences—the 22nd European Hematology Association Annual Congress, the annual American Society of Clinical Oncology meeting and the 14th International Conference on Malignant Lymphoma. And conveniently enough, the data the company presented—one orally and one via a poster—at those three gatherings were about two triple combination therapy trials in cancer.
The trials both featured TG-1101 (ublituximab) and TGR-1202 (umbralisib). TG-1101 is the company's novel, glycoengineered monoclonal antibody, and it targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TGR-1202 is an orally available PI3K delta inhibitor. The delta isoform of PI3K has been found to be strongly expressed in cells of hematopoietic origin, and it's theorized to play a role in the proliferation and survival of B‐lymphocytes.
The oral presentation—“Chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib is well tolerated and highly active in patients with advanced CLL and NHL”—featured data from patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and non-Hodgkin’s lymphoma (NHL) who were relapsed or refractory to prior therapy, with the exception of three CLL patients who were treatment-naive. The patients were treated with a combination regimen of TGR-1202, TG-1101 and ibrutinib. Three cohorts each for CLL/SLL and NHL were assessed with TGR-1202 dose-escalation—starting with 400 mg doses for cohort 1, followed by 600 mg in cohort 2 and 800 mg in cohort 3—administered together with 900 mg of TG-1101 and ibrutinib daily at 420 mg for those with CLL and 560 mg for those with NHL.
Of the participating patients, 38 were evaluable for safety. The combination regimen was well tolerated by all patients, with neutropenia and pneumonia presenting as the only Grade 3/4 adverse events in less than 10 percent of patients. Of the evaluable patients, only two adverse events—sepsis and pneumonia—resulted in treatment discontinuation. As for efficacy, clinical activity was seen at all dose levels in the 36 evaluable patients. Within the CLL/SLL patient subset, there was a 100-percent overall response rate (ORR), including a 32-percent complete response rate (with four of six complete responses pending bone marrow confirmation). One patient who had been refractory to both idelalisib and ibrutinib obtained a complete response that is ongoing for more than 1.5 years.
Of the NHL patients, there was a 100 percent (two of two) ORR, including one complete response, in patients with marginal zone lymphoma; a 100-percent (four of four) ORR, including 50-percent complete response rate, in patients with mantle cell lymphoma; an 80-percent ORR (four of five), including 20-percent complete response rate, in patients with follicular lymphoma; and 17-percent (one of six) ORR in patients with diffuse large B-cell lymphoma (DLBCL).
The poster presentation, titled “Combination of TGR-1202, Ublituximab, and Bendamustine is safe and highly active in patients with advanced DLBCL and Follicular Lymphoma,” featured data from patients with relapsed/refractory DLBCL or follicular lymphoma who were treated with TGR-1202, TG-1101 and bendamustine. The combination regimen seemed to be well tolerated, with no discontinuations for a treatment-related adverse event and no events of pneumonitis or Grade 3/4 transaminitis reported. Within the evaluable patients, there was a 100-percent ORR (four of four), including a 50-percent complete response rate, in patients with relapsed DLBCL, and a 50-percent ORR (six of 12), including a 42-percent complete response rate, in patients with refractory DLBCL with durable complete response and partial responses observed (partial response ongoing for more than 16 months).
While the poster presentation notes that “CD19 CAR-T cell therapy has demonstrated activity in this population,” it adds that “similar limitations of [HD chemotherapy or stem cell therapy] may apply due to aggressive conditioning regimens, significant associated [Grade 3 or higher] AEs and the need to wait several weeks without treatment. By comparison, “Due to its tolerability and activity, the ublituximab + umbralisib combination has served as a backbone regimen in combination with kinase inhibitors, targeted immunotherapy and chemotherapy.”