The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to the tenalisib (RP6530), Rhizen Pharmaceuticals‘ PI3K delta/gamma blocker, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma.
The designation is expected to provide additional regulatory support from the FDA, and makes tenalisib eligible for accelerated approval and priority review, both of which are meant to advance the approval of an investigational therapy.
“We are pleased that RP6530 (tenalisib) has been granted Fast Track Designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our highly selective and orally active dual PI3K delta/gamma inhibitor as an important therapy for patients with relapsed/refractory peripheral T-cell lymphoma (R/R PTCL),” Swaroop Vakkalanka, PhD, founder and president of Rhizen Pharmaceuticals, said in a press release.
Preclinical data has shown that tenalisib can halt the growth of cancer cells while modulating immune cells to acquire anti-tumor characteristics.
Analysis of the RNA content of Hodgkin’s lymphoma cells after tenalisib treatment for six and 24 hours revealed that the inhibitor reduces the levels of genes involved in cell proliferation and survival, and triggers genes associated with cell death.
Tenalisib was also found to block Hodgkin’s lymphoma cells from inducing the activation of tumor-associated macrophages, and promoted the transition of macrophages from an immunosuppressive state into an inflammatory, anti-tumor state.
The findings were recently presented during the 59th Annual ASH Meeting & Exposition Dec. 9-12 in Atlanta, Georgia, in a poster titled “RNA Sequencing Reveals Mechanisms Underlying Modulation of Hodgkin Lymphoma Cells and Tumor Microenvironment By the PI3K δ/γ Inhibitor, RP6530.”
Tenalisib is currently being evaluated in a Phase 1/1b study (NCT02567656) in patients with relapsed or refractory T-cell lymphoma.
As of June 20, 2017, the trial had enrolled 17 patients with peripheral T-cell lymphoma and 20 patients with cutaneous T-cell lymphoma from five clinical sites in the United States.
Nineteen patients were treated twice daily with ascending doses of tenalisib (200 mg, 400 mg, or 800 mg) in a 28-day cycle. The remaining 18 patients were included in an expansion group and treated with 800 mg of the inhibitor. Recruitment in the expansion group is ongoing and researchers hope to reach a total of 40 patients.
Among the first 20 patients who completed at least two cycles of treatment, 45% responded to the treatment, including two complete responses and seven partial responses. Peripheral and cutaneous T-cell lymphoma patients showed similar objective response rates – of 58% and 56%, respectively.
The results were also presented at the 2017 ASH annual meeting in a poster titled “Safety and Anti-Tumor Activity of RP6530, Dual PI3K δ/γ Inhibitor, in Relapsed/Refractory T-cell Lymphoma: Updated Results from the Dose Expansion Cohort of an Ongoing Phase I/Ib Study.”