Golidocitinib Receives Chinese Approval in Relapsed/Refractory PTCL

Golidocitinib monotherapy had a superior clinical benefit in patients with relapsed/refractory peripheral T-cell lymphoma vs existing treatments.

Golidocitinib, a JAK1 selective inhibitor used to treat relapsed/refractory peripheral T-Cell lymphoma (PTCL), has been approved by the National Medical Products Administration in China, according to a news release from the developers, Dizal Pharmaceutical.¹

The decision for approval was made based on results from the multinational pivotal phase 2 JACKPOT8 part B (JACKPOT8B) study (NCT04105010), whereby the golidocitinib monotherapy exhibited superior antitumor efficacy and a favorable safety profile in patients with relapsed or refractory PTCL. Additionally, golidocitinib is the only globally approved JAK1 selective inhibitor for patients with relapsed or refractory PTCL.

Upon data cutoff of August 31, 2023, with a median follow-up 13.3 months, the objective response rate (ORR) was 44.3% (95% CI, 33.7%-55.3%; P <.0001).² Additionally, 26 patients had a complete tumor response with a complete response (CR) rate of 29.5% (95% CI, 203%-40.2%).

"Golidocitinib features 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 demonstrated its favorable pharmacokinetic properties and significant clinical benefit," Jun Zhu, MD, PhD professor in the Department of Lymphoma, Peking University Cancer Hospital and Institute, and lead principal investigator of the JACKPOT8B study, said in the press release.¹ "Golidocitinib achieved an ORR of 44.3% and a [DOR] of 20.7 months in [relapsed/refractory] PTCL. It's approval and market launch provide a much-needed option for doctors to treat [patients with] PTCL."

The primary end point for the JACKPOT8B study was ORR, reviewed by an independent review committee (IRC). Secondary end points included IRC-assessed duration of response (DOR), CR rate, time to response, and progression-free survival (PFS).² Additionally, pharmacokinetic parameters and safety end points, primarily treatment-emergent adverse effects (TEAEs) and serious adverse effects (SAEs) and overall survival (OS) were recorded.

Of 161 patients screened for eligibility, 104 were enrolled, and all were included in the safety analysis and 88 were included in the primary activity analysis.

The median DOR per IRC assessment was 20.7 months (95% CI, 17.6 months-not estimable [NE]), and the median time to first response was 1.4 months (95% CI, 1.4 months–1.5). As of data cutoff, 21 of 39 responders were still responding.

The median PFS was 5.6 months per IRC assessment (95% CI, 3.4-19.1). Furthermore, 58% (n = 51) of patients had survived the duration of the study, with a median OS of 19.4 months (95% CI, 13.1-NE).

In the safety analysis, treatment-emergent adverse effects (TEAEs) of grades 3/4 occurred in 59% of patients. Treatment-related serious adverse effects occurred 24% of patients, with the most common being herpes zoster (3%), pneumonia (3%), and decreased platelet count (3%).

Additionally, drug-related TEAEs led to dose interruption in 38% of patients, dose reduction in 8%, and drug discontinuation in 9%, most of which were managed and reversible. Furthermore, deaths from TEAEs occurred in 3% of patients; 2% to pneumonia, one due to fungal infection and one to COVID-19 infection, and 1% due to a confusional state.

The single-arm, multinational, phase 2 JACKPOT8B trial occurred in 49 centers in Australia, China, South Korea, and the United States. Eligible patients included adults with relapsed or refractory PTCL with at least one previous line of systemic therapy received and an ECOG status of 0-2 with a life expectancy of at least 12 weeks. The activity analysis set included patients who received at least 1 dose and whose pathological diagnosis of PTCL had been confirmed by a central laboratory retrospectively and had at least 1 measurable lesion at baseline.

Patients were given 150 mg of oral golidocitinib once daily until disease progression or discontinuation criteria were met. Prophylactic medicines for pneumocystis pneumonia were required for all patients.

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. Dizel Pharmaceutical; June 19, 2024, Accessed June 19, 2024. https://tinyurl.com/2rname33
2. Song Y, Malpica L, Cai Q, et al. Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. Lancet Oncol. 2024;25:117-125. doi:10.1016/S1470-2045(23)00589-2