A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies

Study Overview
=================
Brief Summary
-----------------
ELiPSE-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety, pharmacokinetics, and preliminary efficacy of CNTY-101 in participants with relapsed or refractory cluster of differentiation (CD)19-positive B-cell malignancies.

Official Title
-----------------
The ELiPSE-1 Study: A Phase 1, Multicenter, Open-Label Study of CNTY-101 in Subjects With Relapsed or Refractory CD19-Positive B-Cell Malignancies

Conditions
-----------------
R/R CD19-Positive B-Cell Malignancies, Indolent Non-Hodgkin Lymphoma, Aggressive Non-Hodgkin Lymphoma

Intervention / Treatment
-----------------
* Biological: CNTY-101
* Biological: IL-2
* Drug: Lymphodepleting Chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of CD19-positive relapsed or refractory (R/R) B-cell Non-Hodgkin's Lymphoma (NHL). Must have met the following criteria for prior treatment: Participants with aggressive NHL must have received at least 2 lines of systemic therapy (if not intended for transplant, have already undergone or be unwilling or unable to undergo chimeric antigen receptor [CAR] T-cell therapy to be eligible), or at least 3 lines of systemic therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylator. Participants with follicular lymphoma (FL) must have received at least 2 lines of systemic therapy and have high-risk disease. Previous therapy must have included a CD20-targeted agent and an alkylator. Participants with marginal zone lymphoma (MZL) must have received at least 2 prior systemic therapies. Measurable disease on screening evaluations. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ function. Life expectancy of ≥12 weeks. Exclusion Criteria: Any condition that confounds the ability to interpret data from the study. Central nervous system (CNS)-only involvement by malignancy. (Note: participants with secondary CNS involvement are allowed.) Prior allogeneic stem cell transplant. Presence of clinically significant CNS pathology. Other comorbid conditions defined in the protocol. Use of prohibited medications within the washout period defined in the protocol.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: Schedule A<br>Lymphodepleting chemotherapy (LDC) will be followed by single dose administration of CNTY-101, alone or with supplemental human recombinant interleukin 2 (IL-2). | Biological: CNTY-101<br>* CNTY-101 cells for intravenous (IV) infusion<br>Biological: IL-2<br>* IL-2 subcutaneous (SQ) injection<br>Drug: Lymphodepleting Chemotherapy<br>* LDC as prespecified in the protocol.<br>|
| Experimental: Dose Escalation: Schedule B<br>LDC will be followed by administration of CNTY-101, 3 times over 3 weeks, alone or with supplemental IL-2. | Biological: CNTY-101<br>* CNTY-101 cells for intravenous (IV) infusion<br>Biological: IL-2<br>* IL-2 subcutaneous (SQ) injection<br>Drug: Lymphodepleting Chemotherapy<br>* LDC as prespecified in the protocol.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) as Determined by the Percentage of Participants With Dose Limiting Toxicities (DLTs) and DLTs Based on Severity |  | Up to 28 days | 
| Recommended Phase 2 Regimen (RP2R) as Recommended by the Safety Review Committee (SRC) |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate (CRR) Based on Percentage of Participants Achieving Complete Response (CR) | CRR will be determined using Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. | Up to 2 years | 
| Objective Response Rate (ORR) Based on Percentage of Participants Achieving CR or Partial Response (PR) | ORR will be determined using Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. | Up to 2 years | 
| Duration of Response (DOR) | DOR is defined as time from first response (CR or PR) to the first documentation of progressive disease (PD) or death. | Up to 2 years | 
| Time to Treatment Response (TTR) | TTR is defined as time from first CNTY-101 infusion to the first documentation of response (CR or PR). | Day 1 up to 2 years | 
| Progression-Free Survival (PFS) | PFS is defined as time from first CNTY-101 infusion to the first documentation of PD, or death from any cause, whichever occurs first | Day 1 up to 2 years | 
| Overall Survival (OS) | OS is defined as time from CNTY-101 infusion to death. | Day 1 up to 2 years | 
| Cmax: Maximum Observed Plasma Concentration for CNTY-101 |  | Day 1 up to 2 years | 
| Tmax: Time to Reach the Maximum Plasma Concentration for CNTY-101 |  | Day 1 up to 2 years | 
| t1/2: Terminal Disposition Phase Half-life for CNTY-101 |  | Day 1 up to 2 years | 
| AUC: Area under the Concentration-time Curve for CNTY-101 |  | Day 1 up to 2 years | 
| Percentage of Participants With at Least one Treatment Emergent Adverse Event (TEAE) |  | Day 1 up to 2 years | 
| Percentage of Participants With Clinically Significant Laboratory Abnormalities |  | Day 1 up to 2 years | 
| Time to Treatment Initiation | Time to treatment initiation is defined as the time from enrollment in the study to first CNTY-101 infusion. | Enrollment to first CNTY-101 infusion (up to approximately 2 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Cellular therapy, Cell therapy, CNTY-101, Century Therapeutics, Induced pluripotent stem cells, CAR-NK, NK cell