Study of Lacutamab in Peripheral T-cell Lymphoma

A Randomized Non Comparative Phase II Study of Lacutamab With GemOx Versus GemOx Alone in Relapsed/Refractory Patients With Peripheral T-cell Lymphoma

This is an open-label multicenter randomized non comparative phase II study to evaluate the safety and efficacy of the monoclonal anti-KIR3DL2 antibody Lacutamab in patients with Refractory/Relapsing (R/R) KIR3DL2 positive Peripheral T Cell Lymphoma (PTCL) : Not Other Specified (NOS), PTCL-TFH (including Angioimmunoblastic T-cell Lymphoma (AITL), Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma (ATL), Hepatosplenic T-cell lymphoma (HSTL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), NK-T cell lymphoma (NKT) and Aggressive NK-cell leukemia (ANKL).

The design is non comparative meaning that non comparison between arms will be performed as the control arm will ensure that the assumptions used for sample size calculation are verified. For that reason, randomization is unbalanced in favor of the experimental arm (2:1).

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral T Cell Lymphoma; Relapse/Recurrence
• Intervention / Treatment: Drug: Lacutamab; Drug: Gemcitabine; Drug: Oxaliplatine

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium
    • Institut Jules Bordet
  • Antwerp, Belgium
    • VZW ZAS
  • Bruges, Belgium
    • A. Z. Sint-Jan
  • Brussels, Belgium
    • Cliniques Universitaires de Bruxelles - Hôpital Erasme
  • Brussels, Belgium
    • Cliniques universitaires Saint-Luc - Université catholique de Louvain
  • Charleroi, Belgium
    • Grand Hôpital de Charleroi
  • Edegem, Belgium
    • UZ Antwerpen
  • Haine-Saint-Paul, Belgium
    • HELORA - Hôpital de La LouvièreSite Jolimont
  • Liège, Belgium
    • Clinique CHC MontLégia
  • Liège, Belgium
    • CHU de LIEGE - Domaine Sart Tilman
  • Verviers, Belgium
    • CHR Verviers
  • Yvoir, Belgium
    • CHU Dinant Godinne - UCL Namur - YVOIR
• France
  • Amiens, France
    • CHU d'Amiens
  • Angers, France
    • CHU d'Angers
  • Avignon, France
    • CH d Avignon - Hopital Henri Duffaut
  • Bayonne, France
    • CH de la Côte Basque - Hôpital de Bayonne
  • Bordeaux, France
    • Institut Bergonie
  • Caen, France
    • CHU de Caen - Côte de Nacre - IHBN
  • Chambéry, France
    • CH Métropole Savoie
  • Clermont-Ferrand, France
    • CHU de Clermont Ferrand - Estaing
  • Créteil, France
    • APHP - Hopital Henri Mondor
  • Dijon, France
    • CHU de Dijon BOURGOGNE - Hôpital François Mitterand
  • Dunkirk, France
    • CH de Dunkerque
  • La Roche-sur-Yon, France
    • CHD de Vendée
  • La Tronche, France
    • CHU de Grenoble - Hopital Albert Michallon
  • Le Chesnay, France
    • Ch de Versailles - Hopital Andre Mignot
  • Le Mans, France, 72000
    • CH du Mans
  • Lille, France
    • Hôpital Saint Vincent-De-Paul
  • Lille, France
    • CHRU de Lille - Hôpital Claude Hurriez
  • Limoges, France
    • Chu de Limoges - Hopital Dupuytren
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Meaux, France
    • Chu de Meaux
  • Montpellier, France
    • CHU de Montpellier
  • Mulhouse, France
    • CH de Mulhouse
  • Nancy, France
    • CHU de Nancy - Brabois
  • Nantes, France
    • CHU de Nantes - Hôtel Dieu
  • Nîmes, France
    • CHU de Nîmes
  • Orléans, France
    • CHR d'Orléans
  • Paris, France
    • APHP - Hopital Necker
  • Paris, France
    • APHP - Hôpital de la Pitié Salpétrière
  • Paris, France
    • APHP - Hôpital Saint Antoine
  • Paris, France
    • APHP - Hôpital Saint Louis
  • Perpignan, France
    • CH de Perpignan
  • Pessac, France
    • CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
  • Pierre-Bénite, France
    • Centre Hospitalier Lyon Sud
  • Poitiers, France
    • CHU de Poitiers - Hôpital de La Milétrie
  • Pringy, France
    • Centre Hospitalier Annecy Genevois
  • Périgueux, France
    • CH de Périgueux
  • Reims, France
    • CHU de Reims
  • Rennes, France
    • CHU de Rennes - Hôpital de Pontchaillou
  • Rouen, France
    • Centre Henri Becquerel
  • Saint-Etienne, France
    • Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne
  • Strasbourg, France
    • Institut de cancérologie Strasbourg Europe
  • Toulouse, France, 31100
    • Institut Universitaire du Cancer de Toulouse - Oncopole
  • Vannes, France
    • CH de Bretagne Atlantique - Hopital Chubert
• Germany
  • Berlin, Germany
    • Charite Universitat Smedizin Berlin
  • Goettigen, Germany
    • GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini
  • Halle, Germany
    • Universitatsklinikum Halle (Saale)
  • Leipzig, Germany
    • UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo
  • Regensburg, Germany
    • UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz - Hematologia
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. KIR3DL2-positive with at least 1% of tumour cells positivity, before randomization, based on central evaluation by immunohistochemistry (IHC) 2. Patients with histologically documented PTCL:

  • Biopsy-proven treated PTCL defined by the WHO 2016 criteria (the biopsy at relapse is recommended but not mandatory):

    • PTCL-NOS
    • PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype)
    • ALCL
    • ATL: acute- or lymphoma-type
    • HSTL
    • EATL
    • MEITL
    • NKT
    • ANKL 3. For patients with ALCL: previously treated with brentuximab vedotin 4. Relapsed/refractory PTCL after at least one previous line of systemic based regimen of chemotherapy (no mandatory latency after the previous treatment) 5. With a maximum of 2 prior lines of systemic therapies, including autologous stem cell transplantation (ASCT is authorized in first and second line and is not counted as a unique line, even if associated to a systemic therapy) 6. Bi-dimensionally measurable disease defined by at least one single node or tumor lesion ≥ 1.5 cm assessed by CT scan 7. Signed written screening informed consent prior to KIR3DL2 screening 8. Signed written study informed consent prior to randomization 9. Aged 18 years or more with no upper age limit, at randomization 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3 prior to prephase treatment (if applicable), and 0 to 2 prior randomization 11. Minimum life expectancy of 3 months 12. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method* from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments 13. FCBP must have a negative serum or urinary pregnancy test within 28 days prior C1D1 14. Male patients and their partner (FCBP) must agree to use two reliable forms of contraception (condom for males and hormonal method for partners) from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments

Exclusion Criteria:

• 1. Patients with active COVID-19 infection (last positive PCR < 2 weeks before randomization) 2. Patients taking immunotherapy or chemotherapy, except short-term corticosteroids in monotherapy at a cumulated dose equivalent of prednisone ≤ 1mg/kg/day, during 7 consecutive days, within 3 weeks prior to first administration of study drug (C1D1); or prephase treatment given at investigator's discretion before randomization and for maximum 3 weeks (glucocorticosteroids, vepesid (VP16), cyclophosphamide, vincristine and prednisone (COP)) 3. Previous treatment by Gemcitabine or Oxaliplatin 4. Use of any experimental anti-cancer drug therapy within 6 weeks before randomization 5. Contraindication to any drug contained in the study treatment regimen 6. Previous allogenic hematopoietic cell transplantation 7. Positive test results for HIV and Hepatitis C Virus (HCV) (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation) 8. Known active hepatitis B (positive Ag HBs) (if latent Hepatitis B Virus (HBV) (positive anti-HBc), patients have to be treated with Entecavir (Baraclude ®) and HBV PCR should be performed every month to allow antiviral strategy adaptation) 9. Central nervous system or meningeal involvement by lymphoma 10. Any of the following laboratory abnormalities prior randomization:

  • Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL
  • Platelet count < 75 G/L, unless thrombopenia is related to PTCL
  • Alkaline Phosphatases > 2.5 x upper limit of normal (ULN)
  • Serum Glutamoyl-oxaloacetate Transferase (SGOT) /Alanine aminotransferase (AST) or Serum Glutamate Pyruvate Transaminase (SGPT)/Alanine aminotransferase (ALT) > 2.5 x ULN
  • Bilirubin > 1.5 x ULN, unless SGOT/AST and SGPT/ALT > 2.5 x ULN or bilirubin elevated due to PTCL or hemolysis
  • Calculated creatinine clearance (MDRD or Cockcroft) < 40 mL/min 11. Any significant cardiovascular impairment: New York Heart Association (NYHA) Class III or IV cardiac disease, uncontrolled high blood pressure, unstable angina, myocardial infarction or stroke within the last 6 months from randomization, and cardiac arrhythmia within the last 3 months from randomization 12. Uncontrolled clinically significant intercurrent illness including, but not limited to, diabetes, ongoing active infections. Patients receiving antibiotics for infections that are under control may be included in the study 13. Concurrent malignancy or prior history of malignancies other than lymphoma unless the subject has been free of disease for ≥ 2 years, except early stage cutaneous squamous or basal cell carcinoma, localized prostate cancer, or cervical intraepithelial neoplasia 14. Major surgery within 4 weeks before randomization 15. Pregnant or lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacutamab; Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase	Drug: Lacutamab; 750 mg/IV; Drug: Gemcitabine; 1000 mg/m²; Drug: Oxaliplatine; 100 mg/m²
Active Comparator: Standard of care; GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase	Drug: Gemcitabine; 1000 mg/m²; Drug: Oxaliplatine; 100 mg/m²

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
median modified progression-free survival (mPFS) - CT-based	time from randomization until one of the following events occurs, whichever comes first: Disease progression (PD); Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)); Relapse after achievement of CR; Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).	5,5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
median modified progression-free survival (mPFS) - PET-based		5,5 years.
Number of Adverse Events		5,5 years.
overall survival (OS)		5,5 years.
complete response rate (CRR) Lugano 2014 criteria (CT-based)		5,5 years.
complete response rate (CRR) Lugano 2014 criteria (PET-based)		5,5 years.
overall response rate (ORR) Lugano 2014 criteria (CT-based)		5,5 years.
overall response rate (ORR) Lugano 2014 criteria (PET-based)		5,5 years.
response rate assessed by Deauville criteria		5,5 years.
duration of response (DOR),	Disease progression (PD); Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)); Relapse after achievement of CR; Death due to any cause	5,5 years.
rate of patients proceeding to allogenic stem cell transplantation		5,5 years.
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		1 month (1 cycle)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		1 month (1 cycle)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		2 months (2 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		2 months (2 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		3 months (3 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		3 months (3 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		7 months (7 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		7 months (7 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		9 months (9 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		9 months (9 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		15 months (15 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		15 months (15 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		26 months (26 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		26 months (26 cycles)
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		29 months (29 cycles)
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		29 months (29 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		1 month (1 cycle)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		2 months (2 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		3 months (3 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		7 months (7 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		9 months (9 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		15 months (15 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		26 months
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		29 months

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Collaborators: Innate Pharma
• Investigators: Study Chair: Morgane Cheminant, Lymphoma Study Association

Publications and helpful links

General Publications

• Cheminant M, Lhermitte L, Bruneau J, Sicard H, Bonnafous C, Touzart A, Bourbon E, Ortonne N, Genestier L, Gaulard P, Palmic P, Suarez F, Frenzel L, Naveau L, Bazarbachi A, Dussiot M, Waast L, Avettand-Fenoel V, Brouzes C, Pique C, Lepelletier Y, Asnafi V, Marcais A, Hermine O. KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target. Blood. 2022 Sep 29;140(13):1522-1532. doi: 10.1182/blood.2022016765.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: July 18, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PTCL; T-cell Lymphoma; KIR3DL2
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Oxaliplatin; Gemcitabine
• Other Study ID Numbers: KILT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No