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

January 26, 2024 updated by: Guangzhou Excelmab Inc.

A Phase I/II Study Evaluating the Safety, Efficacy, and Pharmacokinetics of EX103 in Subjects With Relapsed/Refractory CD20-Positive Non-Hodgkin Lymphoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Based on the safety, tolerability, PK results, and antitumor activity of EX103 in patients with relapsed or refractory CD20-positive non-Hodgkin lymphoma, this study will determine dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) or optimal biological dose (OBD) to provide a basis for the recommended Phase 2 dose (RP2D). The dose expansion phase will further evaluate the safety, tolerability, PK, PD profile, initial antitumor effect, and immunogenicity of several extended cohorts.

Study Type

Interventional

Enrollment (Estimated)

415

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250012
    • Shanghai
      • Shanghai, Shanghai, China, 200233
        • Recruiting
        • Shanghai Sixth People's hospital, Shanghai Jiaotong University School of Medicine
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

-

1. 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:

  1. 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;
  2. Dose-expansion phase:

(i) Cohort 1:

  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;
  2. 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:

  1. Histopathologically and immunohistochemically confirmed CD20-positive follicular lymphoma (FL) (excluding patients whose CD20 turned negative after rituximab treatment);
  2. The histological grade ranged from 1 to 3a;
  3. 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);
  4. Must be indicative of treatment due to symptoms and/or tumor burden;

(iii) Cohort 3:

  1. 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;
  2. 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;
  3. In cases of indolent lymphoma, indications for treatment must be present due to symptoms and/or tumor burden;

4. At the dose escalation and expansion stages, the subjects must have at least one two- dimensionally measurable lesion as the basis for evaluation by CT, or MRI, if CT is not applicable: for intranodal lesions, the long diameter is ≥ 1.5 cm; for extranodal lesions, the long diameter is ≥ 1.0 cm;

5. ECOG performance status score: 0-2;

6. Life expectancy ≥ 12 weeks;

7. The laboratory test results should be met before each cycle beyond cycle 1 (blood components, short-acting cell growth factors, albumin, and other drugs are not allowed to be given within the first 7 days of laboratory tests; long-acting cell growth factors are not allowed to be given within the first 14 days):

  1. Absolute neutrophil count ≥ 1.0×109/L;
  2. Platelet count ≥ 50×109/L;
  3. Hemoglobin ≥ 80 g/L;
  4. Serum total bilirubin ≤ 1.5×ULN; if there is liver invasion, serum total bilirubin ≤ 3×ULN;
  5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver invasion, ALT and AST ≤ 5×ULN;
  6. Serum creatinine ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gault formula ≥ 30 mL/min;

  7. International normalized ratio (INR) or plasma prothrombin time (PT) ≤ 1.5×ULN;

    8. Women of childbearing potential and men with a partner of childbearing potential who consent to use highly effective methods of birth control during treatment and for an additional 90 days after the last administration of the protocol specified treatment; women of childbearing age without surgical sterilization must have a negative result in serum HCG test within 7 days before enrollment in the study and isn't breastfeeding.

    Exclusion Criteria:

    1. Clear history of drug allergy, foreign protein, biologics or ingredients of investigational drugs;
    2. Uncontrolled active infection during the screening period;
    3. 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;
    4. 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;

    5. 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:

      1. Human immunodeficiency virus antibody (HIV-Ab) is negative;
      2. Hepatitis B surface antigen (HBsAg) is negative; when HbsAg or HbcAb is positive, HBV-DNA (HBV deoxyribonucleic acid) is < lower limit of detection;
      3. Hepatitis C virus antibody is positive, and HCV RNA is negative.
    6. 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;
    7. Develop any other malignancy within 5 years (except for completely treated cervical carcinoma in situ or basal cell or squamous cell skin cancer);
    8. Use of any vaccine within 4 weeks prior to initial pretreatment with dexamethasone or methylprednisolone or during the intended study period;
    9. 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.
    10. 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;
    11. Any condition that the investigator believes may not be appropriate for participating in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EX103 injection
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
Administered as specified in the treatment arm.
Other Names:
  • EX103
  • bispecific monoclonal antibody that recognizes both CD3 and CD20

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose Limiting Toxicities (DLTs) [dose escalation (Cycle 0 and Cycle 1)]
Time Frame: During the DLT evaluation period (28 days from Cycle1 Day1 at the dose escalation stage).
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.
Time Frame: 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)].
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
All parts: Time to reach Cmax (Tmax)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Tmax is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Maximum (peak) plasma concentration (Cmax)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Cmax is one of the characteristics of Pharmacokinetic (PK) endpoint.
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)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
AUC0-t is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Elimination half-life (t 1/2)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
t 1/2 is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Total body clearance of drug from the plasma (CL)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
CL is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Steady-state maximum plasma concentration(Css,max)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Css,max is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Steady-state minimum plasma concentration(Css,min)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Css,min is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Steady-state time to maximum concentration(Tss,max)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Tss,max is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Area under the plasma concentration versus time curve at Steady-State(AUCss)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
AUCss is one of the characteristics of Pharmacokinetic (PK) endpoint.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Pharmacodynamic (PD) endpoint
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Before and after administration of EX103, changes in lymphocyte subsets and peripheral blood cytokine levels.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Objective response rate (ORR)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
ORR is defined as the proportion of subjects whose optimal response is CR or CRi or PR. Subjects who did not undergo tumor evaluation after baseline were considered to have no objective, as determined by the investigator using Lugano 2014 criteria.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Disease control rate (DCR)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
DCR is defined as the proportion of subjects whose best response is CR or CRi or PR or SD.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Duration of response (DoR)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Duration of response (DoR) is defined as the time between the first onset of CR or CRi or PR and the onset of PD or death from any cause, whichever occurs first, in subjects with objective response.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Incidence of anti-drug antibodies (ADA)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Percentage of positive patients of anti-drug antibody.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Incidence of neutralizing antibody (NAb)
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Percentage of positive patients of neutralizing antibody.
From first dose until treatment discontinuation, expected average of 3.5 years.
All parts: Confirmation of anti-drug antibody and neutralizing antibodies.
Time Frame: From first dose until treatment discontinuation, expected average of 3.5 years.
Screening of antibodies against corresponding antigens and confirmation of positive antibodies, and determination of the titers of related antibodies (IgG, etc.) produced in the humoral and cellular immunity.
From first dose until treatment discontinuation, expected average of 3.5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Excelmab Inc.

Investigators

  • Principal Investigator: Junyuan Qi, MD, PHD, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2021

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

August 22, 2023

First Submitted That Met QC Criteria

August 28, 2023

First Posted (Actual)

September 1, 2023

Study Record Updates

Last Update Posted (Actual)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 26, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EX103-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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