About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provide signed, written informed consent.

Is male or female, age ≥18 years old (at the time consent is obtained)

For Part 1: Has a histological diagnosis of the following relapsed or refractory PTCL based on WHO 2022 classification of lymphoid neoplasms

Intestinal T-cell and NK cell lymphoid proliferations and lymphomas (without NK cell neoplasms)

Disqualifiers

Is diagnosed with a bulky disease (≥10 cm).

Has known history or presence of central nervous system involvement by leukemia or lymphoma.

Has Mature T-cell and NK-cell leukemias (WHO 2022 criteria)

Has T-lymphoblastic leukemia/lymphoma (WHO 2022 criteria)

Trial design

Design model

Sequential

Treatments tested in this trial

LIS1
Drug
The study intervention (LIS1) is a glyco-humanized polyclonal antibody drug which is formulated for IV administration.

Treatment groups

54 Participants

are divided into 4 treatment groups

Group A: Dose Escalation part: dose 2 mg/kgExperimental treatment 1 intervention

Group B: Dose Escalation part: dose 4 mg/kgExperimental treatment 1 intervention

Group C: Dose Escalation part: dose 6 mg/kgExperimental treatment 1 intervention

Group D: Expansion partExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Dose Escalation part: Dose Limiting Toxicities (DLTs)

Incidence of DLTs in the first cycle

Time frame

At the end of Cycle 1 (28 days)

2

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.

Time frame

After the first dose of study intervention through 60 days following the last dose of study intervention.

3

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.

Time frame

Within 3 months after LIS1 initiation

Secondary outcomes

1

Pharmacokinetics (PK) of LIS: Cmax

LIS1 peak plasma concentration (Cmax) in plasma

Time frame

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.

2

Pharmacokinetics (PK) of LIS: Tmax

Time to peak drug concentration in plasma (Tmax)

Time frame

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.

3

Pharmacokinetics (PK) of LIS: AUC

AUC24hours; AUC0-14days; AUC15-28days and AUC0-28days will be assessed

Time frame

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.

4

Pharmacokinetics (PK) of LIS: Ctrough

Trough concentration (Ctrough) is the concentration reached by LIS1 immediately before the next dose is administered

Time frame

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.

Polyspecific Antibodies in Lymphoproliferative T-cell Disorders

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts