The final results from a national phase 2 study including researchers from Yale Cancer Center show the drug tipifarnib increased survival rates for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The findings are being presented today at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta, Georgia.

Tipifarnib, also called Zarnestra, belongs to the family of drugs called farnesyltransferase inhibitors. It's an older drug developed nearly twenty years ago for use in the treatment of patients with acute myeloid leukemia (AML). "We treated a number of patients on this study at Yale and we observed very dramatic clinical responses in patients who had progressed after chemotherapy and even following stem cell transplants," said Francine M. Foss, MD, Professor Medicine (Hematology) and Dermatology at Yale Cancer Center and senior author of the study. "The activity of tipifarnib was impressive in this group of refractory patients, many of whom had few or no other treatment options."

This study was a multi-institutional, single-arm, open-label trial determining the efficacy, safety, and potential predictive biomarkers for tipifarnib in adult patients with relapsed or refractory (R/R) PTCL. Patients received tipifarnib twice daily for 28-day treatment cycles until progression of disease or unacceptable toxicity.

Sixty-five R/R PTCL patients were treated with tipifarnib nationwide. Fifty-eight patients were efficacy evaluable and had an associated overall response rate (ORR) of 39.7 percent with most responses observed in angioimmunoblastic T-cell lymphoma (AITL) and PTCL- CXCL12 chemokine receptor (CXCL12) + cohorts. In the 32 patients with AITL, the ORR was 56.3 percent, including 9 complete responses (CR) and 9 partial responses (PR). In the 10 patients with PTCL-CXCL12+, the ORR was 40.0 percent, including 1 CR and 3 PR. The median OS for patients with AITL was 32.8 months, and the median OS had not been reached for patients with PTCL-CXCL12+. "One important aspect of this trial was that we explored molecular biomarkers and found that responders could be identified based on expression of the CXCL12 chemokine receptor and a mutated form of the KIR3DL2 receptor," added Foss. "In the era of precision medicine, tipifarnib is emerging as a novel targeted agent, which has high activity even in chemorefractory T cell lymphoma patients whose tumors express these biomarkers."

Thomas E. Witzig, MD, of the Mayo Clinic is lead author of the study.

Funding for the study was provided by Kura Oncology.