Phase 1, Dose-Escalation Study of IGN002 in NHL Subjects

Study Overview
=================
Brief Summary
-----------------
A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Intravenous Doses of IGN002 Administered Weekly to Subjects with Refractory Non-Hodgkin Lymphoma (NHL)

Detailed Description
-----------------
This open-label, non-randomized, first-in-human Phase 1 study involves two stages: In the Dose-Escalation Stage, ascending dose cohorts will be treated in 2 periods until the maximum tolerated dose is identified. In Period 1, subjects will receive 2 doses of IGN002 administered weekly. In Period 2, subjects will receive up to 24 additional doses of IGN002 administered weekly in three 8-week cycles. Subjects that have not progressed following the treatment period will be followed for another 6 months. In the Expansion Stage, subjects will receive up to 24 doses of IGN002 at the identified maximum tolerated dose administered weekly in three 8-week cycles. Subjects that have not progressed following the treatment period will be followed for another 6 months.

Official Title
-----------------
A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Intravenous Doses of IGN002 Administered Weekly to Subjects With Refractory Non-Hodgkin Lymphoma (NHL)

Conditions
-----------------
Non-Hodgkin Lymphoma

Intervention / Treatment
-----------------
* Biological: IGN002


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented history of immunohistochemistry (IHC)-confirmed CD20-positive (with no subsequent history of CD20-negativity) B-cell, NHL, including diffuse large B cell (DLBCL), mantle cell, marginal zone, lymphoplasmacytic, follicular, transformed follicular, or primary mediastinal B cell lymphoma Refractory disease, having failed available therapies Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Life expectancy > 3 months Adequate organ function Exclusion Criteria: Treatment with an approved or investigational chemotherapy drug within 28 days of Day 1 Treatment with an approved or investigational anti-CD20 drug within 28 days of Day 1 Treatment with an approved or investigational biologic drug that does not target CD20 within 90 days of Day 1 Radiation therapy within 4 weeks of Day 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Stage/ Expansion Stage<br>The Dose-Escalation Stage will employ a modified 3 + 3 cohort design, subjects will receive up to 26 doses of IGN002. In the Expansion Stage, subjects will receive up to 24 doses of IGN002 at the maximum tolerated dose administered weekly in three 8-week cycles. | Biological: IGN002<br>* IGN002 is a monoclonal antibody fusion protein.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of multiple doses of IGN002 administered weekly as an intravenous (IV) infusion to subjects with refractory NHL | Adverse Event collection and assessment will be done for all potentially treated subjects to assess the safety, tolerability, and determine the maximum tolerated dose | Weekly for 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the pharmacokinetic (PK) profile of ascending doses of IGN002 administered weekly | Pharmacokinetic (PK) parameters such as Maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration(Cmin), area under the curve (AUC), half-life (t1/2), clearance (CL) | Weekly for 6 months | 
| To assess the anti-tumor activity of IGN002 using the Lugano Classification for NHL | Determine the therapeutic effects, in terms of objective response rate and duration, of the therapeutic agent in NHL patients. | Every 8 weeks for 6 months, then at 1, 3 and 6 months |