Polyspecific Antibodies in Lymphoproliferative T-cell Disorders
NCT Number: NCT06495723
Acronym: PALT1
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Peripheral T Cells Lymphoma (PTCL)
Interventions: DRUG: LIS1
Sponsor: Xenothera SAS
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 54
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-09
Completion Date: 2027-07-31
Locations: CHU de Caen, Caen, 14033, France|CHU de Clermont-Ferrand, Clermont-Ferrand, 63003, France|CHU Henri-Mondor, Créteil, 94000, France|CHU de Bordeaux - GH Sud - Hôpital Haut-Lévêque, Pessac, 33604, France|CHU de Lyon - Hôpital Lyon Sud, Pierre-Bénite, 69310, France

Summary:
This is a 2-part study consisting of a Part 1, dose escalation and dose-finding component to establish the Maximal Tolerated Dose (MTD), or Recommended Part 2 Dose (RP2D) of LIS1 as a single agent; followed by a Part 2, to investigate anti-tumors efficacy of LIS1 in selected subtypes of Peripheral TCell Lymphoma (PTCL) and to further evaluate its safety and tolerability at RP2D.

Primary Outcome Measures: Dose Escalation part: Dose Limiting Toxicities (DLTs), Incidence of DLTs in the first cycle, At the end of Cycle 1 (28 days)|Dose Escalation part: treatment emergent adverse events (TEAEs), The severity of averse events (AEs) will be graded according to the NCI CTCAE, v5.0.

Treatment-emergent adverse events are defined as any AE with onset or worsening of a pre existing condition after the first dose of study intervention through 60 days following the last dose of study intervention., After the first dose of study intervention through 60 days following the last dose of study intervention.|Expansion part: Anti-tumors efficacy, Objective response rate (ORR): defined as the proportion of participants with CR or PR assessed by Investigators according to Lugano criteria with the LYRIC modification for immunomodulatory drug., Within 3 months after LIS1 initiation
Secondary Outcome Measures: Pharmacokinetics (PK) of LIS: Cmax, LIS1 peak plasma concentration (Cmax) in plasma, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: Tmax, Time to peak drug concentration in plasma (Tmax), At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: AUC, AUC24hours; AUC0-14days; AUC15-28days and AUC0-28days will be assessed, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: Ctrough, Trough concentration (Ctrough) is the concentration reached by LIS1 immediately before the next dose is administered, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: Cmin, Cmin for the minimum blood plasma concentration reached by LIS1 during the time interval between administration of two doses, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: T1/2, Half-life (T1/2) refers to the time required for plasma concentration of LIS1 to decrease, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: CL, Clearance (CL) is the volume of blood or plasma cleared of LIS1 from the body per unit of time, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Pharmacokinetics (PK) of LIS: Vd, Volume of distribution (Vd) is defined as the total amount of LIS1 in the body divided by its concentration in plasma, At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.|Host immunogenicity to LIS1, Number of participants who develop detectable anti-drug antibodies, Before and after (up to 5 min after the infusion) LIS1 infusion at Cycle1Day 1, Cycle1Day8, Cycle1Day15, and Cycle1Day22, then before infusion at Day1 and Day15 of Cycle2 to Cycle6 (each cycle is 28 days), and at Day30 and Day60 after last dose of LIS1|Expansion part: treatment emergent adverse events (TEAEs), The severity of averse events (AEs) will be graded according to the NCI CTCAE, v5.0.

Treatment-emergent adverse events are defined as any AE with onset or worsening of a pre existing condition after the first dose of study intervention through 60 days following the last dose of study intervention., After the first dose of study intervention through 60 days following the last dose of study intervention.|Expansion part: Proportion of Complete Response (CR) as best overall response, Proportion of Complete Response as best overall response, Within 3 months and 6 months after LIS1 initiation|Expansion part: Proportion of Partial Response (PR) as best overall response, Proportion of PR as best overall response, Within 3 months and 6 months after LIS1 initiation|Expansion part: Proportion of Stable Disease (SD) as best overall response, Proportion of SD as best overall response, Within 3 months and 6 months after LIS1 initiation|Expansion part: Proportion of Progressive Disease (PD) as best overall response, Proportion of PD as best overall response, Within 3 months and 6 months after LIS1 initiation|Expansion part: Duration of response (DoR), DoR: defined as the time interval between the first confirmed objective response (CR or PR) and the first occurrence of objective progression (PD) or death from any cause., Within 3 months and 6 months after LIS1 initiation|Expansion part: Time to response (TTR), TTR: defined as the time from the date of LIS1 initiation to first confirmed objective response (CR or PR), Within 3 months and 6 months after LIS1 initiation|Expansion part: Progression-free survival (PFS), PFS: defined as the time from the date of LIS1 initiation to the date of first documented progression or death, Within 3 months and 6 months after LIS1 initiation|Expansion part: Overall survival (OS), OS: defined as the time interval between the date of LIS1 initiation and the date of death due to any cause, Within 3 months and 6 months after LIS1 initiation|Expansion part: Proportion of patients "bridged to transplantation", Proportion of patients with a stem cell transplantation after LIS1 treatment, Through study completion, an average of 1 year.