Phase I/II, open-label, multi-center study to evaluate the safety and efficacy of glyco-humanized polyclonal antibody directed against tumoral T cells, in patients with relapsed/refractory peripheral T cells lymphoma (PTCL).

This is a two-part study consisting of a Part 1 dose-escalation and dose-finding phase to determine the potential maximum tolerated dose (MTD) and the recommended Phase 2 dose(s) (RP2D) of LIS1 as a single agent; followed by Part 2, designed to evaluate the antitumor efficacy of LIS1 in selected subtypes of peripheral T-cell lymphoma (PTCL) and to further assess its safety and tolerability at the RP2D. 

Part 1 is a multicenter, open-label, multiple-dose, dose-escalation study to evaluate LIS1 as a single agent in sequential cohorts of adult patients with the following conditions: 

• Intestinal T-cell and NK-cell lymphoproliferative disorders and lymphomas (excluding NK-cell neoplasms) 
• Hepatosplenic T-cell lymphoma 
• Anaplastic large cell lymphoma 
• Nodal follicular helper T-cell lymphoma 

Participants will receive LIS1 once weekly over a 4-week period, which will be classified as induction therapy (Cycle 1). Three planned dose levels will be administered: 2, 4, and 6 mg/kg. Maintenance therapy will be administered at the same dose as induction therapy and will be given every 2 weeks (Q2W) for up to 5 additional cycles (one cycle = 4 weeks [28 days]), or until any of the following occurs: disease progression per Lugano criteria, initiation of a new anti-lymphoma therapy, unacceptable toxicity, symptomatic deterioration, investigator decision to discontinue treatment, participant withdrawal of consent, or sponsor decision to terminate the study. 

A lower dose level (1.5 mg/kg) will be available if toxicity is observed at 2.0 mg/kg, and a 5.0 mg/kg level may be added if toxicity is observed at 2.0 mg/kg. Up to approximately 24 evaluable participants with relapsed or refractory PTCL will be included for dose-limiting toxicity (DLT) assessment. 

This phase will use a modified Bayesian Optimal Interval (mBOIN) design. An accelerated titration cohort (n = 1 evaluable participant for DLT) will be used at the initial dose level, after which dose escalation decisions will proceed using mBOIN rules. Dose escalation will continue until the maximum number of participants is reached overall or at a given dose level. Stopping and escalation rules are described in the statistical methods section. 

The final MTD will be determined by the Safety Committee (SC) based on a comprehensive review of safety data and statistical MTD estimates. The final MTD must not exceed the statistical MTD estimate. After identifying the MTD, backfilling may be implemented to allow treatment and post-baseline evaluation of up to 6 participants at dose levels equal to or below the MTD. Once dose exploration is completed, the scientific committee will make RP2D recommendations based on an integrated clinical assessment of all available safety, tolerability, PK, and preliminary activity data. 

Part 2 is an open-label, non-randomized, multicenter expansion cohort involving approximately 30 evaluable participants. Participants will receive LIS1 at the RP2D determined in Part 1, once weekly for a 4-week induction cycle, then Q2W for 5 cycles, or until disease progression, unacceptable drug-related adverse events (AEs), clinical progression (investigator's judgment), participant withdrawal, or up to 24 weeks. This expansion cohort will study the RP2D to determine the antitumor efficacy, safety, and tolerability of LIS1. The PTCL subtype(s) to be studied in Part 2 will be defined by the SC upon completion of Part 1 and documented in a protocol amendment.