GENUINE progress

NEW YORK—Feb. 23 saw TG Therapeutics, Inc. report the publication of the final results from its Phase 3 GENUINE trial of ublituximab combined with ibrutinib in patients with relapsed or refractory high-risk chronic lymphocytic leukemia (CLL). The results, published in a paper titled “A Phase 3, Randomized Trial of Ublituximab Plus Ibrutinib for Patients With Relapsed/Refractory High-Risk Chronic Lymphocytic Leukaemia,” appeared in The Lancet Haematology.

The results feature data on 126 randomized patients with relapsed or refractory high-risk CLL, 117 of which received at least one dose of treatment and were included in safety analyses, with 59 of those receiving ublituximab plus ibrutinib and 58 receiving ibrutinib monotherapy. Ibrutinib was orally administered at 420 mg for all cycles, while ublituximab was given intravenously in 28-day cycles with up to 150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15 of cycle 1, and continuing at 900 mg on day 1 of cycles 2 through 6. After cycle 6, ublituximab was administered at 900 mg every three months. Treatment with both drugs was continued until patients reached unacceptable toxicity, disease progression, or withdrawn consent. The primary endpoint for this study was independent review committee (IRC) assessed overall response rate (ORR) per iwCLL 2008 criteria.

“The utility of adding anti-CD20 therapy in combination with BTK inhibitors, such as ibrutinib, has long been unclear with prior studies using rituximab having failed to demonstrate an improvement in long-term outcomes. These results published from the GENUINE study are encouraging and may suggest that next generation anti-CD20 antibodies could have value in combination approaches to treating CLL,” remarked Dr. Jeff P. Sharman, director of Research at Willamette Valley Cancer Institute, medical director of Hematology Research for The US Oncology Network, and study chair for the GENUINE trial.

Among treated patients, the IRC-assessed ORR was 90 percent (53 of 59) in the ublituximab-ibrutinib arm and 69 percent (40 of 58) in the ibrutinib arm, with a CR/CRi rate of 20 percent (12 of 59) and 5 percent (3 of 58), respectively. At the median follow-up of 41.6 months, median IRC-assessed progression-free survival (PFS) in treated patients was not reached in the ublituximab-ibrutinib group (95 percent CI, not estimable [NE]) after 15 PFS events, and 35.9 months (95 percent CI, 17·0-NE) in the ibrutinib group after 25 PFS events (hazard ratio [HR], 0.46; 95 percent CI, 0.24-0.87).

“The Phase 3 data published yesterday, and previously presented, demonstrated that the addition of ublituximab to ibrutinib significantly improved overall response rate, complete response rate as well as prolonged progression-free survival,” said Michael S. Weiss, executive chairman and CEO of TG Therapeutics. “Significant unmet need still exists within the CLL landscape, and patients with high-risk relapsed or refractory CLL progress more rapidly than those without high-risk cytogenetics. The outcome of the GENUINE study is therefore very encouraging, and we believe these data are supportive of pursuing combination strategies with ublituximab for high-risk CLL patients.

“We look forward to bringing ublituximab to market as soon as possible as we pursue completion of a BLA submission with the FDA in the first half of 2021 for the combination of ublituximab plus umbralisib for patients with CLL.”

This is the second batch of cancer-related news for the company this month. Earlier in February, TG Therapeutics reported that the FDA had approved UKONIQ (umbralisib) for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. UKONIQ is the first and only, oral, once daily, inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. It received accelerated approval for these indications based on ORR data from the Phase 2 UNITY-NHL trial, and also received Breakthrough Therapy Designation for the treatment of MZL and orphan drug designation for the treatment of MZL and FL.

“Today’s approval of UKONIQ marks a historic day for our company with this being our first approval, and we are extremely pleased to be able to bring our novel inhibitor of PI3K-delta and CK1-epsilon to patients with relapsed/refractory MZL and FL,” Weiss stated in a press release regarding the approval. “We have built a commercial team with significant experience who will immediately start to engage our customers to educate them on UKONIQ and how to access the product for patients in need and expect to make UKONIQ available to US distributors in the next few days.

“We want to thank the patients, physicians, nurses and clinical coordinators for their support and participation in our clinical trials, and the FDA for their collaboration throughout this process. We remain dedicated to patients with B-cell diseases and our mission of developing treatment options for those in need.”

Photo courtesy of National Cancer Institute on Unsplash