Polyspecific Antibodies in Lymphoproliferative T-cell Disorders

NCT06495723 | Recruiting Phase 1 DMC

• 2 other identifiers: XT 23-102023-509648-88-00
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 8

Brief 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.

Conditions

Peripheral T Cells Lymphoma (PTCL)

Keywords

Relapsed Refractory PTCL

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (19)

• Pharmacokinetics (PK) of LIS: Cmax

  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

  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

  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

  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

  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.

Study Arms (4)

Dose Escalation part: dose 2 mg/kg

EXPERIMENTAL

Dose Escalation part: Dose level of LIS1: 2 mg/kg.

Drug: LIS1

Dose Escalation part: dose 4 mg/kg

EXPERIMENTAL

Dose Escalation part: Dose level of LIS1: 4 mg/kg.

Drug: LIS1

Dose Escalation part: dose 6 mg/kg

EXPERIMENTAL

Dose Escalation part: Dose level of LIS1: 6 mg/kg.

Drug: LIS1

Expansion part

EXPERIMENTAL

Expansion part: Participants will receive LIS1 at the RP2D determined in Part 1 of the study.

Drug: LIS1

Interventions

LIS1 DRUG

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

Dose Escalation part: dose 2 mg/kg; Dose Escalation part: dose 4 mg/kg; Dose Escalation part: dose 6 mg/kg; Expansion part

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Hepatosplenic T-cell lymphoma
• Anaplastic large cell lymphoma
• Nodal TFH cell lymphoma
• Other peripheral t-cell lymphomas For Part 2: The type of PTCL will be defined based on SC review after completion of Part 1 and will be documented in the protocol amendment
• Had previously received 1 or more appropriate systemic therapies, including an alkylating agent and/or anthracycline, for treatment of the current disease (radiation therapy alone would not be acceptable as previous therapy). Participants with ALCL must have received prior brentuximab vedotin or be unable to receive it due to allergy or intolerance.
• Experienced disease progression during or after completion of most recent therapy or refractory disease.
• Has a measurable lesion by imaging: the longest diameter should be ≥1.5 cm for nodal lesions and \>1 cm for extra-nodal lesions.
• Experienced a toxicity of prior therapy: Participants must have recovered to less than Grade 1 or to baseline from toxicity of prior chemotherapy or biologic therapy and must not have had major surgery, chemotherapy, radiation, or biologic therapy within 2 weeks prior to beginning treatment.
• Note: Exceptions to this include events not considered to place the participant at unacceptable risk of participation in the opinion of the Investigator (e.g., alopecia).
• Has either unstained tissues (block or unstained slides) or stained slides and pathology report available for central review. If stained slides or unstained tissue are not available or insufficient, a fresh tumor tissue sample is mandatory for central pathology. Central pathology confirmation is not required prior to enrollment.
• Is able to provide a bone marrow aspirate and/or a biopsy no older than 3 months at screening and agrees to undergo post-treatment bone marrow aspirate or biopsy when required to confirm response.

You may not qualify if:

• 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)
• Has tumor-like lesions with T-cell predominance (WHO 2022 criteria)
• Has Primary cutaneous T-cell lymphomas (WHO 2022 criteria)
• Has any other active cancers, or history of treatment for invasive cancer ≤3 years.
• Note: Participants with stage I cancer who have received definitive local treatment at least 3 years previously and are considered unlikely to recur are eligible. All participants with previously treated in situ carcinoma (i.e., non-invasive) are eligible.
• Received any of the following treatments prior to the first dose of study medication:
• Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks (or 5 half-lives, whichever is shorter) before Cycle 1 Day 1. Participants that received local radiation therapy are eligible.
• Therapeutic anti-cancer antibodies \<4 weeks
• Any investigational drug in the last 4 weeks prior
• Any major surgery or immunotherapy within 28 days
• Toxin immunoconjugates \<4 weeks
• Nitrosoureas \<6 weeks

Sponsors & Collaborators

• Xenothera SAS: lead

Study Sites (8)

CHU de Caen

Caen, 14033, France

RECRUITING

CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

CHU Henri-Mondor

Créteil, 94000, France

RECRUITING

CHU de Bordeaux - GH Sud - Hôpital Haut-Lévêque

Pessac, 33604, France

RECRUITING

CHU de Lyon - Hôpital Lyon Sud

Pierre-Bénite, 69310, France

RECRUITING

SC Ematologia Istituto Nazionale dei TumoriIRCCS Fondazione "G. Pascale"

Napoli, Campania, 80131, Italy

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

RECRUITING

Study Officials

• Gandhi-Laurent DAMAJ, MD

  University Hospital, Caen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Françoise SHNEIKER, MD

CONTACT

+33652720301; francoise.shneiker@xenothera.com

Alain BALEYDIER

CONTACT

+33672800375; alain.baleydier@xenothera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: July 11, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 22, 2025

Record last verified: 2025-06

Locations

FR (5); IT (3)