T-Cell Therapy (EB103) in Adults With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (NHL) (STARLIGHT-1)

Estrella Immunopharma, Inc.

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Lymphoma, Non-Hodgkins; Refractory B-Cell Non-Hodgkin Lymphoma; CNS Lymphoma; Large B-Cell Lymphoma; HIV Associated Lymphoma; Relapsed Non-Hodgkin Lymphoma; High-grade B-cell Lymphoma; Lymphoma, Non-Hodgkin; Non-Hodgkin Lymphoma; Lymphomas Non-Hodgkin's B-Cell; Non-Hodgkin's Lymphoma; B-Cell Non-Hodgkin's Lymphoma (NHL); Lymphoma; Refractory Non-Hodgkin Lymphoma; Lymphoma, Non-Hodgkin's, Adult

Treatments: Biological: EB103

Study type: Interventional

Funder types: Industry

Identifiers

NCT06343311

EBUS22CD19AR100

Details and patient eligibility

About

This is an open-label, multi-center, Phase 1/2 clinical trial evaluating the safety and effectiveness of EB103 in R/R B-cell NHL patients with the highest unmet medical needs, such as Human Immunodeficiency Virus (HIV)-associated lymphoma, primary and secondary central nervous system (CNS) lymphoma, and a wide range of high-grade B-cell lymphomas (HGBLs), as well as R/R large B-cell lymphoma (LBCL) patients ineligible for autologous transplant.

Full description

EB103 is an engineered T-cell therapy built on the ARTEMIS® Cell Receptor Platform.

This study consists of a completed Phase 1 portion and an ongoing Phase 2 expansion portion.

In Phase 1, a traditional 3+3 dose-escalation design was used to evaluate the safety and tolerability of EB103 and to determine the recommended Phase 2 dose (RP2D). Following dose escalation, an RP2D confirmatory cohort was enrolled to further characterize the safety profile of EB103 at the selected dose.

Phase 2 is an expansion cohort in which additional subjects will be enrolled and treated at the RP2D to further evaluate the safety and preliminary efficacy of EB103.

The active assessment period extends for 2 years (24 months) after the EB103 infusion (Day 0). Subjects then enter long-term follow-up (LTFU) for ongoing safety and overall survival assessments through Year 15.

Enrollment: 27 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 years or older at the time of informed consent

• Histologically confirmed R/R B-cell non-Hodgkin's lymphoma (NHL)

• Adequate organ function

• Relapsed or refractory disease

  1. Relapsed or refractory disease, defined as ONE OR MORE of the following modified SCHOLAR-1 criteria (Crump, 2017):

     • Progressive disease (PD) as best response to any line of chemoimmunotherapy
     • Stable disease (SD) or partial response (PR) as best response to ≥ 4 cycles of first-line chemoimmunotherapy or to ≥ 2 cycles of later-line chemoimmunotherapy
     • Relapse ≤ 12 months of first-line chemoimmunotherapy

  2. Subjects with PCNSL with following status, if deemed appropriate by the Investigator, can be enrolled:

     • Intolerance of high-dose methotrexate (HD-MTX) induction therapy
     • Subjects ineligible for autologous hematopoietic stem cell transplantation (Auto HSCT) consolidation of HD-MTX-based induction
     • Subjects who have relapsed at any time after Auto HSCT

• Diagnosis and disease assessment

  1. For Non-CNS B-cell NHL Positron emission tomography (PET)-positive disease assessment according to Cheson 2014
  2. For PCNSL or secondary CNS lymphoma shall have the initial diagnosis confirmed by International PCNSL Collaborative Group (IPCG) criteria according to Abrey 2005; Barajas, 2021; Hoang-Xuan 2023.

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Toxicities due to prior therapy must be stable and recovered to Grade 1 or less

• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of informed consent and prior to starting conditioning chemotherapy.

Exclusion criteria

• Prior CD19-targeted cellular therapy
• History of Richter's transformation of chronic lymphocytic leukemia (CLL)
• History of another primary malignancy that has not been in remission for ≥ 2 years.
• History or presence of clinically relevant Central Nervous System (CNS) pathology
• Clinical or radiological evidence of impending brain herniation or significant mass effect
• Those with PCNSL or secondary CNS lymphoma who have previously received whole brain radiotherapy (WBRT)
• Active cardiac lymphoma involvement which is not responding to treatment
• History of myocardial infarction, cardiac angioplasty and stenting, unstable angina, or other clinically significant cardiac disease within 6 months of informed consent
• Active, uncontrolled systemic bacterial, fungal, or viral infection. Patients with HIV, hepatitis B, or hepatitis C are eligible provided their infection is being treated and the viral load is controlled.
• History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• History of severe, immediate hypersensitivity reaction to any agents used in this study, including the conditioning chemotherapeutic agents
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
• Autologous HSCT within 3 months of informed consent
• Prior allogeneic transplant at least 6 months prior to study enrollment are eligible unless experienced graft-versus-host disease (GvHD) that requires ongoing treatment with systemic steroids or other systemic GvHD therapy, such as a calcineurin inhibitor, within 12 weeks of initial screening
• Live vaccine within 3 months prior to planned start of conditioning regimen
• Inability to adhere to all required washout periods for agents and therapies prior to leukapheresis AND prior to starting conditioning chemotherapy
• Female subjects of childbearing potential who are pregnant or breastfeeding; subjects must agree to abstain from breastfeeding during study participation and for ≥ 1 year after lymphodepleting chemotherapy
• In the Investigator's judgement, the subject is unlikely, unable, or unwilling to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
• All genders who are not willing to use acceptable methods of contraception from the time of informed consent through 12 months after EB103 T-cell infusion
• Any medical condition that, in the Investigator's or the Sponsor's opinion, would impose excessive risk to the subject or ability to assess effect of the study drug.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

EB103

Experimental group

Description:

Experimental: Dose Escalation, RP2D Confirmatory, and Expansion (Phase 1/2 Single Arm) Dose Escalation Cohort: Participants receive a single infusion of EB103 at one of two predefined dose levels on Day 0 (completed). RP2D Confirmatory Cohort: Participants receive EB103 at the RP2D on Day 0. Expansion Cohort: Participants receive an initial EB103 T-cell infusion at the RP2D on Day 0 followed by a second EB103 T-cell infusion administered according to the protocol-defined schedule.

Treatment:

Biological: EB103