Safety and Efficacy of EX103 in Subjects with Relapsed/Refractory CD20-Positive Non-Hodgkin Lymphoma

NCT06021678 | Recruiting Phase 1 FDA Drug

• 1 other identifier: EX103-001
• Study Type: interventional
• Target: 415
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multicenter, single-arm, open, dose-escalation Phase I/II clinical trial, consisting of a dose-escalation phase (accelerated titration phase, 3+3 design) and a dose expansion phase.

Conditions

CD20-positive Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicities (DLTs) [dose escalation (Cycle 0 and Cycle 1)]

  To determine the RP2D and the MTD, if reached.

  During the DLT evaluation period (28 days from Cycle1 Day1 at the dose escalation stage).

• Safety endpoints：incidence and severity of adverse events (AE), laboratory tests, etc.

  Treatment-emergent AEs (TEAEs) as assessed by CTCAE v5.0. Abnormal laboratory values are reported as AEs per protocol.

  From first dose until the end of the safety follow-up period [within 28 ± 7 days after the last study treatment or before the start of other anti-tumor treatments (whichever occurs earlier)].

Secondary Outcomes (16)

• All parts: Time to reach Cmax (Tmax)

  From first dose until treatment discontinuation, expected average of 3.5 years.

• All parts: Maximum (peak) plasma concentration (Cmax)

  From first dose until treatment discontinuation, expected average of 3.5 years.

• All parts: Area under the concentration-time curve from time 0 to the last measurable concentration using linear-log trapezoidal rule (AUC0-t)

  From first dose until treatment discontinuation, expected average of 3.5 years.

• All parts: Elimination half-life (t 1/2)

  From first dose until treatment discontinuation, expected average of 3.5 years.

• All parts: Total body clearance of drug from the plasma (CL)

  From first dose until treatment discontinuation, expected average of 3.5 years.

Study Arms (1)

EX103 injection

EXPERIMENTAL

From Cycle 0 to Cycle 2, the subject will receive the preset dose of EX103 once a week (QW), and from Cycle 3, the subject will receive the preset dose of EX103 once every two weeks (Q2W). The recommended dose is MTD or OBD, and a cycle of treatment is 28 days.

Drug: EX103 injection

Interventions

EX103 injection DRUG

Administered as specified in the treatment arm.

Also known as: EX103, bispecific monoclonal antibody that recognizes both CD3 and CD20

EX103 injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Provision of signed and dated informed consent form; stated willingness to comply with all study procedures and availability for the duration of the study; 2. Aged ≥ 18 years old, male or female; 3. Meeting the following criteria:
• Dose-escalation phase: (1) with CD20-positive non-Hodgkin lymphoma confirmed at the first diagnosis (excluding patients whose CD20 turned negative after rituximab treatment); (2) with relapsed or refractory disease after least 2 prior lines of systemic therapy; (3) currently with no suitable therapy available for prolonging survival;
• Dose-expansion phase:
• (i) Cohort 1:
• Histopathologically and immunohistochemically confirmed CD20-positive diffuse large B-cell lymphoma (DLBCL) (excluding patients whose CD20 turned negative after rituximab treatment) : including non-specific (NOS) DLBCL, high-grade B-cell lymphoma (HGBCL), primary mediastinal (thymus) large B-cell lymphoma (PMBCL), and translational follicular lymphoma (trFL) (patients who have converted from follicular lymphoma to DLBCL can be enrolled, and pathology reports should be provided at the same time if there is a disease transformation), or follicular lymphoma (FL) with histological grade 3b; the sponsor may limit the number of patients with PMBCL and trFL enrolled;
• Previous failure or relapse after second-line or higher systemic treatment regimens (at least one of which included anti-CD20 targeted therapy and at least one of which included anthracyclines);
• (ii) Cohort 2:
• Histopathologically and immunohistochemically confirmed CD20-positive follicular lymphoma (FL) (excluding patients whose CD20 turned negative after rituximab treatment);
• The histological grade ranged from 1 to 3a;
• Previous failure or recurrence of second-line or higher systemic regimens (at least one of which included anti-CD20 targeted therapies and alkylating agents; The sponsor may limit the minimum number of patients who are refractory to both anti-CD20-targeted therapies and alkylating agents);
• Must be indicative of treatment due to symptoms and/or tumor burden;
• (iii) Cohort 3:
• Histopathologically and immunohistochemically confirmed CD20-positive non-Hodgkin lymphoma (excluding patients with CD20 turning negative after rituximab treatment), other than the types included in cohort 1 and cohort 2; the sponsor may limit the number of patients with certain or several specific tumor species to be enrolled;
• Previous failure or relapse after second-line or higher standard treatment, at least one of which included a combination of anti-CD20 monoclonal antibodies and chemotherapy agents;
• In cases of indolent lymphoma, indications for treatment must be present due to symptoms and/or tumor burden;

You may not qualify if:

• Clear history of drug allergy, foreign protein, biologics or ingredients of investigational drugs;
• Uncontrolled active infection during the screening period;
• Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplant; or received autologous hematopoietic stem cell transplantation (HSCT) or CAR-T cell therapy within 3 months;
• CNS metastases, or other serious central nervous system diseases (such as epilepsy, cerebral infarction, and cerebral hemorrhage) within 6 months, History of neurodegenerative condition or CNS movement disorder. Subjects with a history seizure within 12 months prior to study enrollment are excluded;
• At least one active person is known to have human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Subjects with evidence below are eligible for study entry:
• Human immunodeficiency virus antibody (HIV-Ab) is negative;
• Hepatitis B surface antigen (HBsAg) is negative; when HbsAg or HbcAb is positive, HBV-DNA (HBV deoxyribonucleic acid) is \< lower limit of detection;
• Hepatitis C virus antibody is positive, and HCV RNA is negative.
• Toxicities caused by previous anti-tumor therapy has not recovered to grade ≤ 1 (CTCAE v5.0), except alopecia and other tolerable events as determined by the investigator;
• Develop any other malignancy within 5 years (except for completely treated cervical carcinoma in situ or basal cell or squamous cell skin cancer);
• Use of any vaccine within 4 weeks prior to initial pretreatment with dexamethasone or methylprednisolone or during the intended study period;
• Systemic immunosuppressive drugs, including but not limited to radiotherapy immune conjugate, antibody drug conjugations, immune/cytokines, monoclonal antibodies, etc., have been used within 4 weeks prior to initial pretreatment with dexamethasone or methylprednisolone.
• With a history of active autoimmune diseases, including but not limited to myocarditis, pneumonia, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, multiple sclerosis, vasculitis, or glomerulonephritis;
• Any condition that the investigator believes may not be appropriate for participating in the study.

Sponsors & Collaborators

• Guangzhou Excelmab Inc.: lead

Study Sites (4)

Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Qilu Hospital, Cheeloo College of Medicine, Shandong University

Jinan, Shandong, 250012, China

RECRUITING

Shanghai Sixth People's Hospital, Shanghai Jiaotong University school of Medicine

Shanghai, Shanghai Municipality, 200233, China

RECRUITING

Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Study Officials

• Junyuan Qi, MD, PHD

  Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiali Lu, MD, PHD

CONTACT

86-02028211020; jiali.lu@excelmab.com

Yanfei Li

CONTACT

86-13242086880; yanfei.li@excelmab.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 1, 2023
• Study Start: November 12, 2021
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Locations

CN (4)