FDA Grants Fast Track Designation Golidocitinib for R/R PTCL Treatment

The FDA has granted fast track designation to the oral, potent JAK1-specific inhibitor, golidocitinib (DZD4205), for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), announced Dizal Pharmaceutical Co, Ltd, in a press release.¹

Phase 1 findings aimed to evaluate the use of golidocitinib in patients with relapsed/refractory PTCL showed a 42.9% tumor response rate, according to the developer.

"Relapsed or refractory peripheral T-cell lymphoma is an aggressive and rare type of non-Hodgkin lymphoma. Patients with [relapsed/refractory] PTCL are often associated with poor prognosis. Couple years ago, our translational science team first identified JAK1 as a potential target for PTCL treatment. Based on the finding, we launched clinical studies to test the hypothesis. Now, we have patient data which validated our translational science finding. This is a great example of translational science-driven drug development," said Dr. Xiaolin Zhang, chief executive officer at Dizal, in a press release. "The FDA fast track designation for DZD4205 is an important milestone and we look forward to working closely with the U.S. FDA to potentially bring this treatment to our patients."

Preliminary findings from the phase 1/2 JACKPOT8 clinical trial (NCT04105010) presented during the 2021 International Conference of Malignant Lymphoma showed tumor responses to 150 mg or 250 mg of golidocitinib in 14 patients, achieving an objective response rate of 51.9%. Of the responses observed, complete responses were seen in 22.2% of patients. The median duration of response was not reached at the time of the analysis, but the longest DOR was greater than 12 months.²

Safety was assessed in all patients, and 87.2% of the patients experienced treatment-emergent adverse events (TEAEs). Grade 3 or greater TEAEs occurred in 51.1% of patients. Thirty-four percent of the high-grade TEAEs were possibly related to golidocitinib, according to the study investigators.

The most common grade 3 or higher TEAEs observed during the study were thrombocytopenia (23.4%), neutropenia (17.0%), and pneumonia (12.8%). The majority of the events appeared to be manageable or reversible, and dose modifications were not needed.

Based on these early findings, investigators predict that golidocitinib may be safe with anti-tumor efficacy in relapsed/refractory PTCL with the potential to fill an unmet medical need for a new therapeutic option.

The analysis was conducted in 47 patients with relapsed/refractory PTCL who had a median age of 62 years (range, 29-79) and received a median of 2 prior lines of therapy (range, 1-8). Six patients from the cohort had undergone hematopoietic stem cell transplant and 16 had bone marrow involvement at baseline. The patient population also had diverse histologic subtypes.

To be included in JACKPOT8, patients must have histologically confirmed disease, measurable disease according to Lugano criteria, be transplant-ineligible, and have adequate bone marrow and organ system functions. Patients may not enroll in the study if they have any unresolved toxicity from prior anti-cancer therapy, active infection, decreased lung function, history of heart failure, central nervous system involvement, history of treatment with a JAK inhibitor, or have undergone allogeneic stem cell transplant.³

JACKPOT8 is ongoing and actively recruiting patients at 51 locations in the United States, Australia, China, and the Republic of Korea.The study is evaluating objective response rate as its primary outcome as well as the secondary end points of incidence of AEs, peak plasma concentration, and area under the plasma concentration versus time curve of golidocitinib.

_References:

_{1. Dizal Pharmaceutical receives U.S. FDA fast track designation for DZD4205 (Golidocitinib) for the treatment of refractory or relapsed peripheral t-cell lymphoma. News release. February 18, 2022. Accessed February 18, 2022. https://bit.ly/3LJAB9L}

_{2. Kim WS, Yoo DH, Song Y, et al. Early safety and efficacy data from a phase I/II trial of dzd4205, a selective jak1 inhibitor, in relapsed/refractory peripheral t‐cell lymphoma .Hematological Oncology. 2021;39(S2):101. doi: 10.1002/hon.57_2879}

_{3. Assessing an oral janus kinase inhibitor, AZD4205 as monotherapy in patients who have PTCL (JACKPOT8). Clinicaltrials.gov. Accessed February 18, 2022.}