Golidocitinib Green Lit by China’s NMPA for Relapsed/Refractory PTCL

China’s National Medical Products Administration (NMPA) has approved the first-in-class selective JAK1 inhibitor golidocitinib (DZD4205) for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) whose disease has progressed on or was refractory to 1 or more prior systemic therapies. The agent is the first JAK1-selective inhibitor to be approved globally for this patient population, according to a press release from the drug’s developer, Dizal Pharmaceuticals.¹

This regulatory decision was supported by results from part B of the multinational pivotal phase 2 JACKPOT8 trial (NCT04105010), in which golidocitinib generated robust and durable antitumor activity and safety across various PTCL subtypes.^1,2 At a median follow-up of 13.3 months (interquartile range, 4.9-18.4), efficacy-evaluable patients (n = 88) treated with golidocitinib experienced an objective response rate (ORR) of 44.3% (95% CI, 33.7%-55.3%; P < .0001) per independent review committee (IRC) assessment, including a complete response (CR) rate of 23.9% (95% CI, 15.4%-34.1%) and a partial response (PR) rate of 20%. Stable disease (19%) and progressive disease (23%) were also experienced by patients. The median duration of response (DOR) was 20.7 months (95% CI, 17.6­–not evaluable), and 53.8% of patients were still responding at the data cutoff of August 31, 2023.

Regarding safety, 92.3% of patients experienced an any-grade treatment-related adverse effect (TRAE), including 59.6% experiencing a TRAE of grade 3 or higher and 24.0% experiencing a serious TRAE. TRAEs leading to dose interruption, reduction, or discontinuation occurred in 38.5%, 7.7%, and 8.7% of patients, respectively. One patient experienced a fatal TRAE.²

These data were simultaneously published in Lancet Oncology and presented at the 2023 ASH Annual Meeting.¹

"Golidocitinib features [a] novel mechanism and unique molecular design, positioning it as the first oral JAK1-only inhibitor for the treatment of relapsed/refractory PTCL. Multiple studies have clearly demonstrated its favorable pharmacokinetic properties and significant clinical benefit," lead study investigator Jun Zhu, MD, PhD, of the Department of Lymphoma at Peking University Cancer Hospital and Institute, stated in the news release. "Golidocitinib achieved an ORR of 44.3% and a DOR of 20.7 months in relapsed/refractory PTCL. Its approval and market launch provide a much-needed option for doctors to treat [patients with] PTCL."

The single-arm JACKPOT8 trial was conducted across 49 treatment centers in Australia, China, South Korea, and the United States (US), enrolling patients with locally diagnosed relapsed/refractory PTCL who were at least 18 years of age, or at least 19 years if they were Korean. An ECOG performance status of 2 or less, adequate organ function, and measurable disease were also required. Additionally, patients with anaplastic large cell lymphoma (ALCL) needed previous exposure to a CD30-targeted therapy.²

Once enrolled, patients received the recommended phase 2 dose of 150 mg of golidocitinib per day in 21-day cycles. Tumor assessment occurred on day 1 of cycle 3, followed by every 3 cycles until disease progression, intolerance to treatment, or withdrawal from the trial. The activity analysis set included all patients who received at least 1 dose of golidocitinib, had a retrospectively confirmed pathologic diagnosis of PTCL, and had 1 or more measurable lesions at baseline per IRC assessment. The safety analysis set included all patients who received at least 1 dose of study drug (n = 104).

The study’s primary end point was ORR per IRC assessment, with key secondary end points including CR rate, DOR, progression-free survival, time to response, pharmacokinetics, and safety.

The Center for Drug Evaluation of the NMPA previously accepted the new drug application for golidocitinib in relapsed/refractory PTCL in September 2023.¹ Additionally, the FDA granted fast track designation to golidocitinib for the treatment of patients with relapsed/refractory PTCL in February 2022.

"We are thrilled to bring golidocitinib, the world's first JAK1-only inhibitor, to patients in China, marking the second approved innovative drug from Dizal," Xiaolin Zhang, PhD, chief executive officer of Dizal, added. "Golidocitinib yields good antitumor efficacy across different subtypes of PTCL, which differentiate golidocitinib from other targeted therapies. At Dizal, we aspire to discover and develop first-in-class and groundbreaking new medicines to address unmet medical needs around the world. With the US FDA fast track designation, we are expediting global development of golidocitinib to bring this exciting drug to patients worldwide."

References

1. Golidocitinib approved in China as first-in-class JAK1 only inhibitor for the treatment of relapsed or refractory peripheral T-cell lymphoma. News release. Dizal. June 19, 2024. Accessed June 19, 2024. https://www.dizalpharma.com/news/detail?id=75&search=&currentPage=1
2. Song Y, Malpica L, Cai Q, et al. Golidocitinib in treating refractory or relapsed peripheral T- cell lymphoma: full analysis of the multinational pivotal study results (JACKPOT8). Blood. 2023;142(suppl1):305. doi:10.1182/blood-2023-172962