Ninety-four percent of patients with chronic lymphocytic leukemia and 79 percent with mantle cell lymphoma responded to treatment with a combination of TGR-1202 (umbralisib), Imbruvica (ibrutinib), and TG-1101, according to updated Phase 1/1b clinical trial results.
The median time for the two groups’ disease to progress ranged from eight months to a year, and their median overall survival rate was about a year, according to TG Therapeutics, which developed TGR-1202 and TG-1101.
The company discussed the new information at the 14th International Conference on Malignant Lymphoma in Lugano, Switzerland, June 14-17. The presentation was titled “Updated results of a multicenter phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed or refractory MCL or CLL.”
Both TGR-1202 and Imbruvica are oral protein kinase inhibitors. TGR-1202 blocks the PI3K delta protein, which impairs the immune system, and Imbruvica the BTK protein, which is also involved in immune function.
TG-1101 is an anti-CD20 monoclonal antibody. It targets problems in immune-system B-cells’ response to cancer.
“We continue to be impressed with the safety, tolerability and activity of the combination of TGR-1202 and ibrutinib,” Michael S. Weiss, TG Therapeutics’ CEO, said in a news release. “With this all oral combination, we are seeing high response rates, including in those patients with prior PI3K inhibitor or ibrutinib exposure. Additionally, the combination was well tolerated, with over 30 patients now treated, and for durations upwards of 2.5 years in this independently run, investigator-initiated study.”
Researchers evaluated the combo therapy’s effectiveness in 31 patients — 17 with leukemia and 14 with lymphoma. They evaluated its safety with 32 patients — 18 with leukemia and 14 with lymphoma. Thirty-one patients were involved in both assessments.
The leukemia patients had received a median of 1 1/2 previous treatment regimens, with some regimens involving Imbruvica or other PI3K inhibitors. The lymphoma patients had received a median of three prior therapies, some of which included Imbruvica.
Ninety-four percent of the leukemia patients responded completely or partially to the combo treatment. Eight-percent achieved disease-progression-free survival for at least a year, and 94 percent at least a year’s overall survival.
Seventy-nine percent of the lymphoma group responded to the combo therapy. Their median progression-free survival was 8.4 months and their median overall survival 11.6 months.
The combo therapy was safe, and patients tolerated it well. There were no reports of severe liver toxicity, diarrhea, colitis, or pneumonitis.
It was significant that 26 percent of the leukemia patients achieved a complete response to the therapy, Weiss noted. “We look forward to continuing to explore these combinations to drive better outcomes for patients,” he said.