IPH4102 Alone or in Combination With Chemotherapy in Patients With Advanced T Cell Lymphoma

Study Overview
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Brief Summary
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This is an open label, multi-cohort, and multi-center phase II study, which evaluates the clinical activity and safety of IPH4102 in Sezary Syndrome and Mycosis fungoides as single agent.

Official Title
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TELLOMAK: T-cell Lymphoma Anti-KIR3DL2 Therapy. An Open Label, Multicohort, Multi-center Phase II Study Evaluating the Efficacy and Safety of IPH4102/Lacutamab Alone or in Combination With Chemotherapy in Patients With Advanced T-cell Lymphoma

Conditions
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Lymphoma, T-Cell, Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides/Sezary Syndrome

Intervention / Treatment
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* Biological: IPH4102


Participation Criteria
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Eligibility Criteria
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Inclusion criteria SS patients (Cohort 1): Relapsed and/or refractory stage IVA, IVB SS who have received at least two prior systemic therapies; Prior treatment with mogamulizumab; Patients should have blood stage B2 at screening based on central evaluation by flow cytometry; Feasibility of obtaining at least one skin biopsy at screening; MF patients (Cohorts 2 and All comers): Relapsed and/or refractory stage IB, IIA, IIB, III, IV MF; Only for Cohort 2: KIR3DL2 expression in at least one expressing skin lesion based on central evaluation by IHC; Patients should have received at least two prior systemic therapies; Feasibility of obtaining at least one skin biopsy at screening; Additional inclusion criteria applicable to all cohorts: Male or Female, at least 18 years of age; ECOG performance status ≤2; The patient must have a minimum wash-out period of 3 weeks between the last dose of prior systemic therapy and the first dose of IPH4102; Patients should have recovered from all non-hematological adverse events related to prior therapy to ≤ grade 1 except for alopecia; Adequate baseline laboratory data: Hematology: Hemoglobin >9 g/dL, Absolute neutrophil count (ANC) ≥1,500/µL, Platelets ≥100,000/µL, Biochemistry: Bilirubin ≤1.5 X upper limit of normal (ULN) or ≤3 X ULN for patients with Gilbert's disease, Serum creatinine ≤1.5 X ULN, Creatinine clearance ≥30 mL/min, calculated with the Cockcroft & Gault formula, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 X ULN; Women of childbearing potential (WOCBP): Premenopausal females who had at least one menstrual cycle in the past 12 months and capable to become pregnant. They must have a negative serum beta-HCG pregnancy test result within seven days from start of treatment; Women of childbearing potential and all men (and their female partners of childbearing potential) who are sexually active must agree to use adequate method of contraception at study entry, during treatment and for at least 9 months (270 days) following the last dose of study drug; Signed informed consent form prior to any protocol-specific procedures Exclusion Criteria: Patients with evidence of large cell transformation (LCT) based on central histologic evaluation at screening; Receipt of live vaccines within 4 weeks prior to treatment; Central nervous system (CNS) lymphoma involvement; Prior administration of IPH4102; Concurrent enrollment in another clinical trial, unless it is an observational (non - interventional) clinical study or the follow-up period of an interventional study; Autologous stem cell transplantation less than 3 months prior to enrollment; Prior allogenic transplantation; Patients who have undergone major surgery ≤ 4 weeks prior to study entry; Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection; Patients who have Hepatitis B Virus infection determined as HBsAg positive and / or Hepatitis C Virus infection determined as detection of HCV RNA in serum or plasma by a sensitive quantitative molecular method; Known or tested positive for human immunodeficiency virus (HIV); Patients with a history of other malignancies during the past five years apart from the disease subject of this study. The following are exempt from the five-year limit: non-melanoma skin cancer, lymphomatoid papulosis, resected thyroid cancer, biopsy-proven cervical intraepithelial neoplasia, Ductal carcinoma in situ (DCIS) or cervical carcinoma in situ Pregnant or breastfeeding women; Known clinically significant cardiovascular disease or condition, including: Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) Functional Classification; Any uncontrolled arrhythmia (per the investigator's discretion); Uncontrolled hypertension (per the investigator's discretion). Patients with autoimmune disease on systemic immunosuppressive treatment; Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol; Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Relapsed/refractory Sezary Syndrome<br>IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. | Biological: IPH4102<br>* Patients will receive a flat dose of 750mg<br>* Other names: lacutamab;|
| Experimental: Cohort 2: Stage IB-IV Mycosis Fungoides, KIR3DL2 expressing<br>IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. | Biological: IPH4102<br>* Patients will receive a flat dose of 750mg<br>* Other names: lacutamab;|
| Experimental: Cohort 3: Stage IB-IV Mycosis Fungoides,KIR3DL2 non-expressing (closed)<br>IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. | Biological: IPH4102<br>* Patients will receive a flat dose of 750mg<br>* Other names: lacutamab;|
| Experimental: Cohort All comers: Stage IB-IV Mycosis Fungoides,KIR3DL2 expressing and non-expressing<br>IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. | Biological: IPH4102<br>* Patients will receive a flat dose of 750mg<br>* Other names: lacutamab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Using the Olsen (2011, JCO) criteria (All cohorts) | From the first dose until study completion, an expected average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) (All cohorts) | patients with treatment-related adverse events as assessed by CTCAE v5.0 | From first dose until study completion, an expected average of 2 years | 
| Quality of life (QoL) (All cohorts) | Using the Skindex29 questionnaire to assesse the effects of skin disease on quality of life in three domains: Symptoms, Emotions, and Functioning | Through study completion, an expected average of 2 years | 
| pruritus (All cohorts) | Using Visual Analog Scale (VAS) for prutitus assessment: From 0 = No pruritus to 10 = Pruritus as bad as it could possibly be | Through study completion, an expected average of 2 years | 
| ORR using blinded central review (Cohort 1) | Using the Olsen (2011, JCO) criteria | From the first dose until study completion, an expected average of 2 years | 
| Progression free survival (PFS) (All cohorts) |  | From the first dose until study completion, an expected average of 2 years | 
| Overall survival (OS) (All cohorts) |  | From the first dose until study completion, an expected average of 2 years | 
| PK parameters : Maximum Plasma Concentration of IPH4102 alone (All cohorts) | Maximum Plasma Concentration (Cmax) (W1, W5) | From the first dose until study completion, an expected average of 2 years | 
| PK parameters :Trough Concentration of IPH4102 alone (All cohorts) | Trough Concentration (Ctrough) every 8 or 12 weeks | From the first dose until study completion, an expected average of 2 years | 
| Immunogenicity of IPH4102 alone (All cohorts) | A serum sample will be collected at the specified time points for evaluation of anti-drug antibodies (ADA). | From the first dose until study completion, an expected average of 2 years | 
| Duration of Response (DOR) |  | From the first dose until study completion, an expected average of 2 years |