Golidocitinib combined with CHOP in newly-diagnosed peripheral T-cell lymphoma: Preliminary Results from A phase 1/2 clinical trial

Abstract

Abstract Background： Peripheral T-cell lymphoma (PTCL) comprises a group of heterogeneous and aggressive non-Hodgkin lymphomas associated with poor outcomes. CHOP remains the standard first-line therapy, yet the 5-year overall survival (OS) remains suboptimal. Golidocitinib, a potent and selective JAK1 inhibitor, has demonstrated promising anti-tumor activity with favorable safety profile in relapsed/refractory (r/r) PTCL. Aims： To evaluate the anti-tumor activity and tolerability of Golidocitinib in combination with CHOP regimen (Go-CHOP) as the frontline therapy for patients with PTCL. Methods： This is an ongoing phase 1/2, single-center, single-arm clinical trial (NCT06739265) evaluating Go-CHOP as first-line therapy in adults patients (≥18 years) with histologically confirmed, previously untreated PTCL, including PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), etc. The study consists of two sequential phases: a 3+3 dose-escalation cohort (Phase 1) to determine the recommended phase 2 combination dose (RP2CD), followed by a dose-expansion cohort (Phase 2) assessing efficacy and safety. In Phase 1, patients receive six 21-day cycles of Go-CHOP: oral golidocitinib 150 mg every other day (Qod) on days 1-21 combined with standard CHOP chemotherapy (cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m² IV on day 1, and prednisone 100 mg po on days 1-5). Dose escalation to 150 mg once daily was permited if ≤1/6 patients experienced dose-limiting toxicities (DLTs) during cycle 1, defined as grade 4 hematological toxicity lasting ≥7 days or grade ≥3 non-hematological events (per CTCAE v5.0). In Phase 2, patients received Go-CHOP at the RP2CD. Interim PET-CT was performed after 3 cycles. Responders at the end of Go-CHOP therapy received either consolidative autologous stem cell transplantation (ASCT), if eligible, or golidocitinib maintenance for transplant ineligible patients for up to 24 months or until disease progression or unacceptable toxicity. The primary endpoint is complete response rate (CRR) assessed according to the Lugano 2014 criteria, at the end of Go-CHOP therapy. Results： As of the data cutoff on August 3rd, 2025, eighteen patients were enrolled and received at least one cycle of Go-CHOP regimen, including 6 patients in phase 1 and 12 patients in phase 2. The median age was 50 years (range, 18-70), and 14 patients (77.8%) were male. All eighteen patients (100%) had stage III-IV disease, and eleven (61.1%) had an IPI score of 3-5. Diagnoses included: AITL in 9 patients (50%), PTCL-NOS in 7 (38.9%), MEITL in 1 (5.6%), and ALK+ALCL in 1 (5.6%). No DLTs were observed in the dose escalation phase, establishing 150 mg golidocitinib once daily as RP2CD. Treatment-related adverse events (TRAEs) were observed in 17 patients (94.4%), with neutropenia being the most common one (72.2%), followed by urinary tract infection (22.2%) and thrombocytopenia (22.2%). Grade 3/4 TRAEs were primarily neutropenia, observed in 61.1% of the patients. CMV reactivation was observed in 3 patients (16.6%) and warrants close monitoring. Additionally, one case of hepatitis B virus reactivation and one case of pulmonary cryptococcosis were reported, the latter resulting in treatment discontinuation. One fatal case of gastrointestinal bleeding was reported, which was assessed as unrelated to the treatment by the investigator. Among 15 efficacy-evaluable patients, 12 achieved objective responses, and 11 reached CR, yielding an overall response rate (ORR) of 80.0% and a CRR of 73.3%. With a median follow-up of 5.5 months, the median progression-free survival and OS will be reported after longer follow-up. Conclusion: Preliminary results of golidocitinib in combination with CHOP demonstrated a manageable safety profile and encouraging antitumor activity in newly diagnosed PTCL. This clinical trial is ongoing.