A Study of BEBT-908 in Combination With Chemotherapy in Patients With Previously Untreated Peripheral T-Cell Lymphoma (PTCL)

Previously Untreated Peripheral T-Cell Lymphoma

BEBT-908, PTCL, Safety, Pharmacokinetics, Efficacy

The goal of this clinical study is to find the best way to combine the study drug BEBT-908 (ifupinostat hydrochloride for injection) with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for treating previously untreated peripheral T-cell lymphoma, and to find out whether this best combination is better than standard CHOP treatment alone. The main questions this study will try to answer are: What percentage of participants will respond well to treatment with BEBT-908 plus CHOP? Is BEBT-908 plus CHOP better than standard CHOP treatment? What medical problems will participants have while receiving this combination treatment? This study includes an Exploration Phase and an Expansion Phase. The Exploration Phase has 3 cohorts. All participants receive both BEBT-908 and CHOP, but the dosing arrangements differ across cohorts: the dose of BEBT-908 differs, the sequencing of administration differs, and whether participants continue with CHOP or transition to BEBT-908 depends on their tolerability to CHOP. Eligible participants will receive the combination treatment for their assigned cohort. After that, based on the results from all 3 cohorts in the Exploration Phase, one optimal cohort will be selected to proceed into the Expansion Phase. In the Expansion Phase, eligible participants will be randomly assigned (like flipping a coin) in a 1:1 ratio to either the treatment group, receiving the optimal combination regimen identified in the Exploration Phase, or the control group, receiving 6 cycles of CHOP. This study design will help investigators find the best way to combine BEBT-908 and CHOP for treating previously untreated peripheral T-cell lymphoma, and check whether this optimal combination regimen is better than standard CHOP treatment.

This study is an open-label, multicenter Phase II clinical study designed to evaluate the efficacy, safety, and pharmacokinetic profile of BEBT-908 in combination with CHOP in patients with previously untreated peripheral T-cell lymphoma (PTCL), and to explore the relationship between tumor biomarkers and the efficacy and safety of BEBT-908 plus CHOP. The study consists of an Exploration Phase and an Expansion Phase. Exploration Phase: Eligible participants are stratified by pathological subtype and enrolled into 3 study cohorts. Each treatment cycle is 21 days. The cohorts are as follows: Cohort 1: BEBT-908 (8.2 mg/m²)in combination with CHOP for 6 cycles. This cohort follows a "3+3" design. The first 3 participants are enrolled, and based on the safety and tolerability findings from Cycle 1 of these participants, the investigator will determine whether to proceed with subsequent cycles and whether to continue enrolling additional participants. Cohort 2: CHOP for 2 cycles, followed by BEBT-908 (18.5 mg/m²) for 4 cycles, followed by CHOP for 4 cycles. All enrolled participants in this cohort receive CHOP during cycles 1-2. Regardless of response, all participants switch to BEBT-908 (18.5 mg/m²) starting from Cycle 3 for consecutive 4 cycles. After these 4 cycles, participants without progressive disease (PD) will then receive CHOP for 4 more cycles. Cohort 3: BEBT-908 (18.5 mg/m²) for 4 cycles, followed by CHOP for 2-6 cycles or BEBT-908 (18.5 mg/m²) for 4 more cycles. All enrolled participants in this cohort receive BEBT-908 (18.5 mg/m²) during cycles 1-4. After 4 cycles, participants without progressive disease (PD) will subsequently receive either CHOP or BEBT-908 depending on their clinical situation. Participants who are intolerant to CHOP chemotherapy will continue to receive BEBT-908 (18.5 mg/m²) for 4 more cycles. Participants who are tolerant to CHOP will receive CHOP treatment, with the number of cycles determined as follows: participants achieving complete response (CR) after 4 cycles of BEBT-908 will receive 2 to 4 cycles of CHOP (as determined by the investigator based on individual assessment); participants achieving partial response (PR) or stable disease (SD) after 4 cycles of BEBT-908 will receive 6 cycles of CHOP. Upon completion of treatment in each cohort, participants without PD may continue receiving BEBT-908 (18.5 mg/m²) and enter a maintenance treatment phase for up to 24 months. Participants who are in CR will continue BEBT-908 treatment (the preferred approach is to maintain the original BEBT-908 dosing schedule; however, based on participant preference and investigator assessment, the dosing frequency may be reduced). Participants who are in SD or PR will also continue BEBT-908 treatment. Expansion Phase: Based on the efficacy and safety results from the Exploration Phase, the investigator and sponsor will jointly select one optimal cohort to proceed into the Expansion Phase. This phase uses an open-label, multicenter, randomized controlled design, with stratification by pathological subtype: angioimmunoblastic T-cell lymphoma (AITL) vs. non-AITL. About 60 eligible participants will be randomized in a 1:1 ratio to either the experimental arm or the control arm. Participants in the experimental arm will receive the dosing regimen of the optimal cohort identified in the Exploration Phase; Participants in the control arm will receive 6 cycles of CHOP. Participants enrolled in both the Exploration Phase and the Expansion Phase will go through three study periods: the screening period, the treatment period, and the follow-up period. Participants will: Receive study treatment according to their assigned cohort regimen for a maximum duration of 24 months; Undergo periodic tumor assessments and safety evaluations during the study.

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