Clinical trial NCT06484985: Study of AXT-1003 in Subjects with Advanced Malignant Tumors.
Official title: An Open-label, Multicenter, Phase I Safety Study of AXT-1003 in Subjects with Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Hodgkin Lymphoma
Advanced Solid Tumor
Keywords: AXT-1003
EZH2
Phase I
Advanced malignancies
Lead sponsor: Axter Therapeutics (Beijing) Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-07-03
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I study of AXT-1003 to assess the safety, tolerability, and pharmacokinetics in patients with advanced malignancies.

Detailed description: AXT1003-1102 is a multicenter, open-label, Phase I safety study of AXT-1003 in patients with advanced malignancies. It is designed to observe the safety of AXT-1003 in patients with advanced malignancies, determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), evaluate the pharmacokinetic profile, and explore the preliminary antitumor activity.

Eligibility criteria: Inclusion Criteria:

1. For Ia dose escalation part only:

   R/R NHL: Locally histopathological diagnosis of relapsed/refractory non-Hodgkin lymphoma (R/R NHL), who have progressed or been intolerant after the available standard therapies, or have no access to the standard therapies.

   Advanced solid tumors: Locally histopathological diagnosis of locally advanced unresectable and metastatic solid tumors,The above subjects have progressed or been intolerant after the available standard therapies, or have no access to the standard therapies.

   For Ib dose expansion part only: Subjects with relapsed/refractory peripheral T-cell lymphoma (R/R PTCL)
2. Eastern Cooperative Oncology Group (ECOG) performance status scale 0 to 1.
3. Have a life expectancy of at least 3 months.
4. For Ib dose expansion part and not mandatory for Ia dose escalation part: Subjects with R/R NHL must have measurable lesions as defined by Lugano 2014 criteria. Subjects with advanced solid tumors must have measurable or evaluable lesions as defined by RECIST 1.1.
5. Adequate organ and bone marrow functions.
6. The adequate washout period for prior therapy .
7. Subjects must use a highly effective contraception method throughout the study and for 3 months after discontinuation of the study drug.
8. Signed ICF and willing to comply with all the requirements in the protocol.

Exclusion Criteria:

1. Received treatment with compounds with the same mechanism of action (EZH2 inhibitor, EZH1/EZH2 inhibitor etc.).
2. Diagnosis of precursor B-cell lymphoblastic leukemia/lymphoma, precursor T-cell lymphoblastic leukemia/lymphoma, precursor NK cell lymphoblastic leukemia/lymphoma. Diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL).
3. Central nervous system infiltration.
4. Uncontrolled or significant cardiovascular disease.
5. Major surgery within 4 weeks before the first dose of study drug.
6. Known or suspected hypersensitivity to AXT-1003 or any of the excipients.
7. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of AXT-1003.
8. History of other malignancies prior to enrollment; except for subjects with basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or other carcinomas in situ who have undergone possible curative treatment and do not have disease recurrence within 5 years since starting the treatment.
9. Any prior treatment-related clinically significant toxicities that have not resolved to Grade ≤ 1 or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrollment.
10. Active infection requiring systemic treatment.
11. Infection with hepatitis B virus with positive hepatitis B surface antigen, or hepatitis C virus with detectable anti-hepatitis C circulating viral RNA.
12. Subjects known to be infected with human immunodeficiency virus and active tuberculosis.
13. Females who are pregnant or breastfeeding.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation)
timeFrame: Up to 28 days
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Baseline up to 30 days after the last dose of study
Secondary outcomes:
measure: Overall response rates (ORR)
timeFrame: Up to 3 years
measure: Duration of response(DOR)
timeFrame: Up to 3 years
measure: Progression free survival (PFS)
timeFrame: Up to 3 years
measure: Time to response (TTR)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Maximum observed concentration (Cmax) of AXT-1003
timeFrame: Up to 15 days
measure: Time of maximum observed concentration (tmax) of AXT-1003
timeFrame: Up to 15 days
measure: Area under the curve from the time of dosing to the time of the last measurable concentration (AUCtau) of AXT-1003
timeFrame: Up to 15 days
measure: Minimum observed concentration (Cmin) of AXT-1003
timeFrame: Up to 15 days
measure: Terminal elimination half-life (t1/2) of AXT-1003
timeFrame: Up to 15 days
measure: Total body clearance (CL/F) of AXT-1003
timeFrame: Up to 15 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hosptial
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Axter Therapeutics (Beijing) Co., Ltd
name: Qin Gao
role: STUDY_DIRECTOR
References: