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

Guangzhou Excelmab Inc.4 sites in 1 country415 target enrollmentNovember 12, 2021

ConditionsCD20-positive Non-Hodgkin Lymphoma

InterventionsEX103 injection

DrugsEX103 injection

Overview

Phase: Phase 1
Intervention: EX103 injection
Conditions: CD20-positive Non-Hodgkin Lymphoma
Sponsor: Guangzhou Excelmab Inc.
Enrollment: 415
Locations: 4
Primary Endpoint: Incidence of Dose Limiting Toxicities (DLTs) [dose escalation (Cycle 0 and Cycle 1)]
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

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.

Registry

clinicaltrials.gov

Start Date

November 12, 2021

End Date

December 2025

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Guangzhou Excelmab Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of signed and dated informed consent form; stated willingness to comply with all study procedures and availability for the duration of the study;
•Aged ≥ 18 years old, male or female;
•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);

Exclusion Criteria

•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);

Arms & Interventions

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.

Intervention: EX103 injection

Outcomes

Primary Outcomes

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.

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.

Secondary Outcomes

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.)
All parts: Steady-state maximum plasma concentration(Css,max)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Steady-state minimum plasma concentration(Css,min)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Steady-state time to maximum concentration(Tss,max)(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)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Pharmacodynamic (PD) endpoint(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Objective response rate (ORR)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Disease control rate (DCR)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Duration of response (DoR)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Incidence of anti-drug antibodies (ADA)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Incidence of neutralizing antibody (NAb)(From first dose until treatment discontinuation, expected average of 3.5 years.)
All parts: Confirmation of anti-drug antibody and neutralizing antibodies.(From first dose until treatment discontinuation, expected average of 3.5 years.)