Maintenance Therapy of Golidocitinib, a JAK1 Selective Inhibitor, in Patients with Peripheral T Cell Lymphomas after First-Line Systemic Therapy: Updates of the Phase 2 Study (JACKPOT26)

Introduction:

For PTCL patients who achieved tumor response with first-line standard therapy, the relapse rate remains high. Approximately 40% of patients with complete response and 80% of patients with partial response had disease relapse within 2 years after initial tumor response, and the prognosis of relapsed patients was very poor. Golidocitinib, a JAK1 selective inhibitor, was recently approved in China for the treatment of relapsed or refractory (r/r) PTCL. We explored golidocitinib as maintenance therapy for PTCL patients who achieved tumor response after first-line systemic therapy (JACKPOT26, NCT06511869). In ASH 2023 annual meeting, we reported preliminary data of this study, which showed a manageable safety profile and encouraging antitumor efficacy. Here we reported the updated results with longer follow-up.

Methods:

PTCL patients who achieved tumor response post first-line therapy were enrolled and received golidocitinib treatment at 150 mg once daily (QD). This study included two cohorts: cohort 1 (complete response) and cohort 2 (partial response). The objectives were to assess safety and antitumor efficacy of golidocitinib as maintenance therapy. The efficacy endpoints included the rate of patients who were 1-year and 2-year disease free survival (DFS) for cohort 1, and progression free survival (PFS), objective response rate (ORR), duration of response (DoR) for cohort 2, respectively. Tumor response was assessed by investigators based on CT images per Lugano 2014 criteria. Endpoints for safety assessments are treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs), etc.

Results:

As of June 28, 2024, a total of 48 patients with PTCL were enrolled, including 30 patients with complete response (cohort 1) and 18 patients with partial response (cohort 2). The median age was 58.5 years (range: 25 to 74), and 52.1% were male. Major pathological subtypes included: AITL (31.3%), NOS (27.1%) and NK/TCL (27.1%). All dosed patients were included in the efficacy and safety analysis.

In cohort 1 (CR), with median follow-up of 19.7 months, median DFS has not been reached, and the 12-month and 18-month DFS rates were 82.1% and 78.2%, respectively. In nodal subtypes (AITL, NOS, ALK-ALCL), with median follow-up of 20.0 months, median DFS has not been reached. In cohort 2 (PR), 7 out of 18 patients (38.9%) achieved complete response with golidocitinib treatment. The median DoR has not been reached, with the estimated 18-month DoR rate of 68.6%. The median PFS was 17.6 months.

The safety profile of golidocitinib was similar to what has been reported previously. The most common ≥ grade 3 drug-related TEAEs were hematological adverse events in nature, including neutropenia (47.9%), leukopenia (31.3%), lymphopenia (12.5%) and thrombocytopenia (6.3%). The majority of these TEAEs were reversible and clinically manageable. Four patients discontinued golidocitinib treatment due to drug-related TEAEs. No drug-related TEAEs leading to fatal outcomes were reported.

Conclusions:

With longer follow-up, golidocitinib continued to demonstrate a manageable safety profile and promising effect on maintaining and enhancing tumor response in patients with PTCL post first-line therapies. This result suggested potential better clinical outcomes with golidocitinib maintenance therapy than real-world results. The updated data will be presented at the conference.

No relevant conflicts of interest to declare.