Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor (TKI), showed encouraging anti-tumour activity in heavily pre-treated patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) in the phase I study JACKPOT8. The results of the phase II, recently published in Lancet Oncology, demonstrated a favourable benefit–risk profile of golidocitinib in this patient population, warranting further investigation.
Golidocitinib showed encouraging anti-tumour activity in heavily pre-treated patients with R/R PTCL in the phase I study JACKPOT8 (part A). Based on these promising results, the phase II of this study (JACKPOT8 part B) analysed the anti-tumour activity of golidocitinib in a large multinational cohort of patients, using the recommended phase II dose defined in part A.1,2
Methods
JACKPOT8 part II is a single-arm, multinational, phase II trial conducted in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were aged ≥18 years with R/R PTCL who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was objective response rate (ORR). The activity analysis set included all patients who received at least one dose, whose pathological diagnosis of PTCL had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug.
Findings
In total, 161 patients were assessed for eligibility, of whom 104 (65%) were enrolled and received at least one dose of the study drug. The activity analysis set included 88 (85%) patients. After a median follow-up of 13.3 months, ORR was reported at 44.3% (39 of 88 patients, p<0.0001), with 21 (24%) patients having a complete response and eighteen (20%) having a partial response. In the safety analysis set, 61 (59%) of the 104 patients had grade 3-4 drug-related treatment-emergent adverse events (TEAEs). The most common grade 3–4 drug-related TEAEs were neutrophil (29%), white blood cell (26%), lymphocyte (21%), and platelet (20%) count decreased, which were clinically manageable and reversible. Twenty-five (24%) patients had treatment-related serious AEs. Deaths due to TEAEs occurred in three (3%) patients, two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state.
Conclusions
In this phase II study, golidocitinib showed a favourable benefit–risk profile in treating patients with R/R PTCL. The results of this study warrant further investigation of golidocitinib to confirm activity and assess efficacy in this population.2
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