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Addition of ublituximab to ibrutinib improves response in high-risk CLL
A phase 3 study designed to evaluate the combination of ublituximab plus ibrutinib in patients with previously treated high-risk chronic lymphocytic leukemia met its primary endpoint.
The addition of ublituximab (TG-1101, TG Therapeutics) — a highly potent next-generation glycoengineered anti-CD20 monoclonal antibody — to ibrutinib (Imbruvica; Pharmacyclics, Janssen), a Bruton’s tyrosine kinase inhibitor, increased overall response rate by more than 70% compared with ibrutinib alone.
“The addition of ublituximab to ibrutinib enhances the therapeutic benefit of ibrutinib in patients with previously treated high-risk CLL, the patient population with the poorest outcome on ibrutinib,” Michael S. Weiss, executive chairman and CEO of TG Therapeutics, said in a company-issued press release. “We believe the results observed in the combination arm are extremely compelling, and the regimen has the potential to become the standard of care for treating patients with high-risk CLL that have progressed from other therapies.”
The randomized, open-label, multicenter phase 3 GENUINE trial evaluated the safety and efficacy of ublituximab plus ibrutinib compared with ibrutinib alone in 126 adults with high-risk CLL who received at least one prior therapy.
All study participants received 420 mg oral ibrutinib once daily. Fifty-nine patients also received 900 mg ublituximab via IV infusions on days 1, 8 and 15 of cycle 1, followed by day 1 of cycles 2 through 6. Study participants assigned ublituximab who did not progress during the treatment phase received quarterly infusions of 900 mg ublituximab maintenance.
Median follow-up was approximately 12 months.
Researchers reported a significantly higher ORR in the ublituximab group (80% vs. 47%; P < .001). Ublituximab-treated patients also demonstrated improvements in radiographic complete response rate, PFS and time to response.
The combination exhibited a safety profile consistent with that reported in a prior study.
“Ibrutinib has been a great addition to our CLL armamentarium; however, we have long believed that ibrutinib alone may not be enough, particularly for patients with high-risk disease,” study chair Jeff Sharman, MD, medical director for hematology research for US Oncology Network, said in the press release.
“This study demonstrates that the addition of ublituximab can significantly enhance the response rates without compromising safety,” Sharman added. “We believe that the rapid responses seen in our phase 2 study with ublituximab plus ibrutinib are validated here in our phase 3 GENUINE study and are important markers of improved overall efficacy and patient outcomes.”
A full analysis of the phase 3 study, including detailed safety and efficacy data, will be submitted for presentation at a medical meeting later this year.
“We believe that using combination therapy to accelerate and deepen response in poor-prognosis high-risk CLL is critically important for patient outcomes, and we look forward to sharing these data with the FDA in the coming months to discuss filing for accelerated approval,” Weiss said.