Phase1/2 Study of IPH6501 in Patients With Relapsed /Refractory B-Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is an international, first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety profile, tolerability of IPH6501, and determine the recommended phase 2 dose (RP2D) for patients with B-Cell non-Hodgkin lymphoma.

Detailed Description
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In Phase 1 - Dose finding, patients with advanced histologically confirmed, documented CD20+ B-cell non-Hodgkin lymphoma (NHL) will be enrolled. The dose finding part will include 2 sub-parts: Dose escalation will determine the Maximum Tolerated Dose (MTD) or the highest tested dose, Dose assessment will determine RP2D. In Phase 2 - Dose expansion, one or more cohorts will be selected with patients with subtypes of advanced histologically confirmed, documented CD20+ B-cell non-Hodgkin lymphoma.

Official Title
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A Phase 1/2, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of IPH6501 in Patients With Relapsed and/or Refractory CD20-expressing Non-Hodgkin Lymphoma

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: IPH6501


Participation Criteria
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Eligibility Criteria
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Main Inclusion criteria Patients with advanced histologically confirmed, documented CD20+ B-cell non-Hodgkin's lymphoma (NHL) including the following types defined by WHO 2016: Diffuse Large B Cell Lymphoma (DLBCL); high grade; thymic; Follicular Lymphoma (FL); Mantle cell lymphoma (MCL); Marginal zone lymphoma (MZL) Relapsed, progressive and/or refractory disease without established alternative therapy Must have received at least 2 prior systemic therapies including at a minimum anti-CD20 antibody therapy (e.g., rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Adequate organ and hematological function Able to provide a fresh biopsy from a safely accessible site (or historical biopsy), per investigator determination. Main Exclusion Criteria Patients with another invasive malignancy in the last 2 years Prior chemotherapy, immunotherapy or other anti-cancer therapy within less than 4 weeks before study drug administration. Autologous stem cell transplant or treatment with CAR-T (Chimeric Antigen Receptor T-Cell) cell therapy within 100 days prior to first dose of study drug Subjects with brain or subdural metastases are not eligible, nor those with history of central nervous system (CNS) lymphoma Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B or C Major surgery within 4 weeks before the first dose of study drug Comorbidities including diabetes, cardiovascular diseases, immunodeficiencies/autoimmune condition Pregnant / breastfeeding woman

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPH6501 monotherapy<br> | Drug: IPH6501<br>* phase 1 (dose finding) and phase 2 (dose expansion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | To evaluate the safety profile (including dose limiting toxicities (DLT(s), the maximum tolerated dose (MTD) or highest tested dose), tolerability and determine the recommended phase 2 dose (RP2D) | From time of informed consent through treatment period and including the follow-up: up to 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | To investigate any preliminary antitumor activity | From time of informed consent through treatment period and including the follow-up: up to 22 months | 
| Duration Of Response (DoR) | To investigate any preliminary antitumor activity | From time of informed consent through treatment period and including the follow-up: up to 22 months | 
| Progression Free Survival (PFS) | To investigate any preliminary antitumor activity | From time of informed consent through treatment period and including the follow-up: up to 22 months | 
| Maximum Observed Plasma Concentration (Cmax) | To characterize and evaluate the pharmacokinetic profile of IPH6501 | From time of informed consent through treatment period and including the follow-up: up to 22 months | 
| Area Under the Plasma Concentration (AUC) | To characterize and evaluate the pharmacokinetic profile of IPH6501 | From time of informed consent through treatment period and including the follow-up: up to 22 months | 
| Incidence of antidrug antibodies (ADA) against IPH6501 | To evaluate the immunogenicity of IPH6501 | From time of informed consent through treatment period and including the follow-up: up to 22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ANKET®, NK cell engager, tetraspecific NK cell engager