Study of Lacutamab in Peripheral T-cell Lymphoma

Inclusion Criteria:

1. KIR3DL2-positive with at least 1% of tumour cells positivity, beforerandomization, 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 atrelapse is recommended but not mandatory):
• PTCL-NOS
• PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-celllymphoma with TFH phenotype)
• ALCL
• ATL: acute- or lymphoma-type
• HSTL
• EATL
• MEITL
• NKT
• ANKL 3. For patients with ALCL: previously treated with brentuximabvedotin 4. Relapsed/refractory PTCL after at least one previous line ofsystemic based regimen of chemotherapy (no mandatory latency after theprevious treatment) 5. With a maximum of 2 prior lines of systemictherapies, including autologous stem cell transplantation (ASCT isauthorized in first and second line and is not counted as a unique line,even if associated to a systemic therapy) 6. Bi-dimensionally measurabledisease defined by at least one single node or tumor lesion ≥ 1.5 cmassessed by CT scan 7. Signed written screening informed consent prior toKIR3DL2 screening 8. Signed written study informed consent prior torandomization 9. Aged 18 years or more with no upper age limit, atrandomization 10. Eastern Cooperative Oncology Group (ECOG) performancestatus 0 to 3 prior to prephase treatment (if applicable), and 0 to 2prior randomization 11. Minimum life expectancy of 3 months 12. Females ofchildbearing potential (FCBP) must agree to use highly effectivecontraceptive method* from C1D1, during the entire study period, duringdose interruptions, and for 9 months after the last study treatments 13.FCBP must have a negative serum or urinary pregnancy test within 28 daysprior C1D1 14. Male patients and their partner (FCBP) must agree to usetwo reliable forms of contraception (condom for males and hormonal methodfor partners) from C1D1, during the entire study period, during doseinterruptions, and for 9 months after the last study treatments

Exclusion Criteria:

1. Patients with active COVID-19 infection (last positive PCR < 2 weeks beforerandomization) 2. Patients taking immunotherapy or chemotherapy, exceptshort-term corticosteroids in monotherapy at a cumulated dose equivalent ofprednisone ≤ 1mg/kg/day, during 7 consecutive days, within 3 weeks prior tofirst administration of study drug (C1D1); or prephase treatment given atinvestigator's discretion before randomization and for maximum 3 weeks (glucocorticosteroids, vepesid (VP16), cyclophosphamide, vincristine andprednisone (COP)) 3. Previous treatment by Gemcitabine or Oxaliplatin 4. Use ofany experimental anti-cancer drug therapy within 6 weeks before randomization
2. Contraindication to any drug contained in the study treatment regimen 6.Previous allogenic hematopoietic cell transplantation 7. Positive test resultsfor HIV and Hepatitis C Virus (HCV) (Patients who are positive for HCV antibodymust 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 strategyadaptation) 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 bilirubinelevated due to PTCL or hemolysis

• Calculated creatinine clearance (MDRD or Cockcroft) < 40 mL/min 11. Anysignificant cardiovascular impairment: New York Heart Association (NYHA) ClassIII 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 notlimited to, diabetes, ongoing active infections. Patients receiving antibioticsfor infections that are under control may be included in the study 13.Concurrent malignancy or prior history of malignancies other than lymphomaunless the subject has been free of disease for ≥ 2 years, except early stagecutaneous squamous or basal cell carcinoma, localized prostate cancer, orcervical intraepithelial neoplasia 14. Major surgery within 4 weeks beforerandomization 15. Pregnant or lactating females