Study of AXT-1003 in Adult Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas

NCT05965505 | Terminated Phase 1

• 2 other identifiers: AXT1003-1101CTR20231973
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, multicenter, phase I study of AXT-1003 to assess the safety, tolerability, and pharmacokinetics in adult subjects with Relapsed/Refractory Non-Hodgkin Lymphomas.

Conditions

Relapsed or Refractory Non-Hodgkin's Lymphoma

Keywords

NHL; EZH2 inhibitor; Phase I; Peripheral T-cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation)

  Dose Escalation only: to characterize the dose limiting toxicities (DLTs) of AXT-1003.

  Up to 28 days

• Number of Participants with Adverse Events (AEs) by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment.

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Participants with multiple occurrences of an AE within a category were counted once within the category. Relatedness to study drug was assessed by the investigator.

  Baseline up to 30 days after the last dose of study drug

• Number of Participants with Clinically Significant Change from Baseline in Laboratory Abnormalities by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

  Laboratory parameters included: hematology, blood chemistry, urinalysis and coagulation. Clinical significance of laboratory parameters was determined at the investigator's discretion.

  Baseline up to 30 days after the last dose of study drug

Secondary Outcomes (13)

• Overall response rates (ORR)

  Up to 3 years

• Duration of response(DOR)

  Up to 3 years

• Progression free survival (PFS)

  Up to 3 years

• Time to response (TTR)

  Up to 3 years

• Disease control rate (DCR)

  Up to 3 years

Study Arms (1)

AXT-1003

EXPERIMENTAL

Dose Escalation: Level 1 (Starting Dose) Oral AXT-1003 100 mg BID; Level 2 Oral AXT-1003 200mg BID; Level 3 Oral AXT-1003 300mg BID ; Level 4 Oral AXT-1003 450mg BID; Level 5 Oral AXT-1003 600mg BID; Level 6 Oral AXT-1003 750mg BID Dose Expansion: 1 or 2 cohorts at the dose levels selected from dose escalation part

Drug: AXT-1003

Interventions

AXT-1003 DRUG

AXT-1003 capsule is administered orally daily, until disease progression or intolerable toxicity.

AXT-1003

Eligibility Criteria

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

You may qualify if:

• Female or male subjects aged ≥ 18 years.
• Histopathological diagnosis of relapsed/refractory non-Hodgkin lymphoma \[R/R NHL\] (except for CLL/SLL), who have progressed after treatment with approved therapies or who have no access to approved or standard therapies.
• Note 1: Refractory is defined as failure to:
• Achieve complete response after first-line therapy
• Reach at least partial response after second-line therapy or beyond. Note 2: Subjects must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
• For dose expansion part: Subjects with pathologically confirmed R/R NHL by the local pathologist/investigators are enrolled. Most of the enrolled subjects are confirmed with R/R PTCL subtype. Local histological diagnosis will be used for eligibility determination. Subjects with PTCL are eligible according to 2016 World Health Organization (WHO) classification, including but not limited to the following subtypes:
• PTCL, not otherwise specified.
• Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) positive
• Anaplastic large cell lymphoma, ALK negative
• Angioimmunoblastic T-cell lymphoma
• Extranodal NK-/T-cell lymphoma, nasal type The subjects enrolled in the dose expansion part should be progressed after treatment with approved therapies or who have no access to approved or standard therapies.
• Eastern Cooperative Oncology Group performance status scale 0 to 1.
• Have a life expectancy of at least 3 months.
• Have measurable disease as defined by Lugano 2014 criteria, subjects must have measurable lesions (nodal lesion with any long diameter \> 1.5 cm, or extranodal lesion with any long diameter \> 1.0 cm) (not mandatory for the dose escalation stage).
• Willing to provide archived or fresh tumor tissue samples that are sufficient for EZH2 status detection (not mandatory).

You may not qualify if:

• Diagnosis of precursor B-cell lymphoblastic leukemia/lymphoma, precursor T-cell lymphoblastic leukemia/lymphoma, precursor NK cell lymphoblastic leukemia/lymphoma.
• Diagnosis of CLL, SLL.
• Diagnosis of Burkitt lymphoma.
• Received treatment with compounds with the same mechanism of action (EZH2 inhibitor, EZH1/EZH2 inhibitor etc.).
• Central nervous system infiltration.
• Clinically significant GVHD or GVHD requiring systemic immunosuppressive prophylaxis or treatment.
• Uncontrolled or significant cardiovascular disease, including:
• Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT corrected for heart rate using Fridericia's method \> 470 msec) (average of triplicate determinations).
• Diagnosed or suspected long QT syndrome or known family history of long QT syndrome.
• History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
• Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial fibrillation may be enrolled) or asymptomatic persistent ventricular tachycardia.
• History of second- or third-degree heart block. Subjects with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers within 6 months prior to screening.
• Myocardial infarction within 6 months prior to screening.
• Angioplasty or stent craft implantation within 6 months prior to screening.
• Uncontrolled angina pectoris within 6 months prior to screening.

Sponsors & Collaborators

• Axter Therapeutics (Beijing) Co., Ltd: lead

Study Sites (4)

Beijing Cancer Hospital

Beijing, China

Location

West China Hospital, Sichuan University

Chengdu, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell

Study Officials

• Yanfang Guo

  Axter Therapeutics (Beijing) Co., Ltd

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 28, 2023
• Study Start: August 11, 2023
• Primary Completion: September 5, 2023
• Study Completion: September 5, 2023
• Last Updated: August 1, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)