FDA Fast Track Designation Granted to Tipifarnib for T-Cell Lymphomas

The FDA has granted a fast track designation to tipifarnib for the treatment of adult patients with relapsed or refractory T-cell lymphomas, according to a press release from Kura Oncology, Inc. The fast track designation includes patients with relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL), follicular T-cell lymphoma (FTCL), and nodal peripheral T-cell lymphoma with a T follicular helper (TFH) phenotype.¹

The fast track designation follows the presentation of preliminary results from a phase II trial of tipifarnib in relapsed/refractory T-cell lymphomas at the 2019 ASH Annual Meeting.²

The single-arm, open-label trial included 50 patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). Patients had received a median of 3 prior treatment regimens and 19 patients had undergone a prior stem cell transplant.

Nineteen patients were treated in the first 2 stages of the trial and the remainder were included in an ongoing cohort examining patients with AITL or PTCL and wild-type CXCL12 3'UTR. All patients received 300 mg twice daily of oral tipifarnib.

Eighteen patients in stages 1 and 2 were evaluable for response and 3 of these patients achieved a partial response and 5 other patients had stable disease. Of 11 evaluable patients in the AITL cohort, an overall response rate (ORR) of 45% was observed with a clinical benefit rate (CBR) of 73%. In the wild-type CXCL12 3'UTR cohort, an ORR of 42% was observed and 2 of the 3 patients who achieved a complete response had AITL histology.

Among patients harboringKIR3DL2gene variants C336R/Q386E, a 50% complete response rate was observed as well as a 75% ORR and 100% CBR.

Treatment-emergent adverse events (TEAEs) were observed in each of the 48 evaluable patients treated in the study. Frequent grade >3 TEAEs included neutropenia (40%), thrombocytopenia (33%), leukopenia (25%), and anemia and febrile neutropenia (19% each). Of 14 deaths during the study, only 1 due to a lung infection was considered to be related to treatment.

Tipifarnib, a selective inhibitor of farnesyl transferase, waspreviously granted a fast track designation from the FDAfor the treatment of patients withHRAS-mutant head and neck squamous cell carcinoma (HNSCC) who had progressed on prior platinum therapy.

“This important designation from the FDA comes just 2 months after tipifarnib was awarded fast track for the treatment of patients withHRAS-mutant HNSCC,” Bridget Martell, MA, MD, acting chief medical officer of Kura Oncology, said in a statement. “We believe that this designation reflects tipifarnib’s significant potential in these devastating disease settings, and we are now actively preparing to initiate a second registration-directed trial of tipifarnib in advanced nodal lymphomas of TFH phenotype, including AITL.”

The single-arm, multi-center trial will be initiated this year and is expected to enroll approximately 128 patients with AITL or similar histologies who have relapsed following or are refractory to at least one prior systemic regimen. In addition to a co-primary end point of ORR in the total patient population, the study will also be examining the ORR in patients withKIR3DL2genetic variants.

References

1. Kura Oncology Receives Fast Track Designation for Tipifarnib in T-Cell Lymphomas [news release]. San Diego, CA: Kura Oncology, Inc.; March 3, 2020. https://bit.ly/2uSJL1i. Accessed March 3, 2020.
2. 2) Witzig TE, Sokol L, Foss FM, et al. Proof of Concept for Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-Cell Lymphoma (AITL) and CXCL12+ Peripheral T-Cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study.Blood. 2019;134(Supplement_1):468. doi: 10.1182/blood-2019-128513.