To Evaluate a Phase I/II Clinical Study of XNW5004 Tablets in Patients With Relapsed/Refractory Advanced Tumors

NCT06558513 | Completed Phase 1 FDA Drug

• 1 other identifier: XNW5004-I/II-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with advanced tumors diagnosed histologically or cytologically at the study center who were refractory to standard therapy or had relapsed received XNW5004 tablets

Conditions

Advanced Tumor; Lymphoma

Keywords

EZH2 inhibitor; XNW5004

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment-emergent adverse events (AEs)[Safety and Tolerability]

  The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of XNW5004 will be assessed.

  through study completion, an average of about 10 months

• Recommended phase 2 dose (RP2D)

  Recommended phase 2 dose (RP2D) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of XNW5004.

  28 days since the date of first dose in phase 1

Secondary Outcomes (11)

• Time to peak (Tmax)

  28 days since the date of first dose

• Maximum plasma concentration (Cmax)

  28 days since the date of first dose

• Halflife (T1/2)

  28 days since the date of first dose

• Objective response rate (ORR)

  every 8 weeks through study completion, an average of about 10 months

• Progression-free survival (PFS)

  every 8 weeks through study completion, an average of about 10 months

Study Arms (1)

XNW5004

EXPERIMENTAL

Phase 1：treated with escalated doses of XNW5004 respectively； Phase 2：treated with RP2D of XNW5004 respectively

Drug: XNW5004 tablets

Interventions

XNW5004 tablets DRUG

XNW5004 an EZH2 inhibitor, BID, administered in continuous

XNW5004

Eligibility Criteria

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

You may qualify if:

• Age: ≥ 18 years old; Gender unlimited
• Pathologically confirmed, relapsed or refractory non Hodgkin's lymphoma (NHL). The definition of recurrence and refractory is as follows: Recurrence: After achieving remission, NHL meets the conditions for disease progression. For B-NHL patients, they should undergo a two line drug treatment regimen (with the first line containing CD20 monoclonal antibody), or a second line systemic treatment regimen that is not suitable/tolerated (such as toxic side effects, etc.); For T-NHL, first-line systemic chemotherapy should be administered, or if systemic chemotherapy is intolerant, and a regimen containing targeted CD30 drugs (including but not limited to Vibutuximab) or cetuximab should be administered. Refractory: Systemic medication treatment with at least two regimens and a total course of no less than 4 cycles of dose standard has not achieved partial remission.
• At least one measurable lesion should be used as the evaluation basis
• Has a life expectancy of ≥12 weeks;
• The ECOG score is 0-1;
• The functional reserve of important organs meets the following requirements: (1) Hematopoietic function: a) Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L (≥ 0.5 × 10\^9/L for those with bone marrow infiltration) (G-CSF was not used within one week before the screening period blood routine examination, and long-acting white needle was not used within two weeks); b) Platelet count ≥ 75 × 10\^9/L (≥ 50 × 10\^9/L for those with bone marrow infiltration) (no platelet transfusion or TPO receptor agonist used within one week before the screening period blood routine examination); c) Hemoglobin ≥ 90 g/L (bone marrow infiltration requires ≥ 70 g/L) (no red blood cells were transfused or EPO was used within one week before the screening period blood routine examination); (2) Liver function: serum total bilirubin ≤ 1.5 x ULN (Gilbert's syndrome ≤ 3 ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN, ALT/AST ≤ 5 x ULN for patients with liver infiltration, and alkaline phosphatase ≤ 5 x ULN for patients with liver and/or bone infiltration; (3) Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance rate estimated based on Cockcroft Gault formula ≥ 60 mL/min (Cockcroft Gault formula, see Appendix 5 for details); (4) Left ventricular ejection fraction (LVEF) ≥ 50%; (5) International standardized ratio (INR) or plasma prothrombin time (PT) ≤ 1.5 x ULN, partial thromboplastin time (APTT) ≤ 1.5 x ULN.
• Non surgical sterilization or female patients of childbearing age, as well as male subjects whose partners are female of childbearing age, are required to use a medically approved contraceptive measure (such as an intrauterine device, contraceptive pill, or condom) within 6 months after the screening period and the end of the study treatment period; Non surgically sterilized female patients of childbearing age must have a negative serum HCG test within 7 days prior to enrollment in the study, and must be non lactating;
• Prior to conducting research specific procedures, provide a written informed consent form with a signature and date, and be able to comply with clinical visits and research related procedures.

You may not qualify if:

• Patients who have previously received treatment with drugs similar or related to the investigational drug pathway (such as EZH 1/2 or EZH2 inhibitors);
• Those who have received anti-tumor treatment in the early stage but have not recovered their toxicity (according to NCI-CTCAE 5.0, the toxicity has not recovered to ≤ 1 level). Other toxicities that the researchers believe do not affect the safety evaluation of the subjects, such as hair loss, are excluded;
• Have a history of other malignant tumors within the 5 years prior to enrollment and do not meet clinical cure criteria. The following cases are excluded: skin basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast intraductal carcinoma in situ and thyroid papillary carcinoma that can be treated locally and have been cured.
• Impaired heart function or clinically severe heart disease, including any of the following: (1) Acute myocardial infarction or unstable angina before first administration ≤ 6 months; (2) Congestive heart failure (New York Heart Association classification of heart function as III or IV); (3) Uncorrected severe arrhythmia and hypertension ≥ 150/100mmHg; (4) Extended QTc interval (defined as\>450ms in males and\>470ms in females) (Fredericia's formula); (5) Have a history of other major cardiovascular diseases (such as valve replacement surgery, coronary artery bypass grafting surgery, etc.).
• Severe systemic active infection;
• HIV positive and syphilis (Anti TB) positive individuals;
• HBsAg positive and HBV-DNA copy number higher than the normal upper limit of detection value; Or HBcAb positive and HBV-DNA copy number higher than the normal upper limit of detection value; HCV antibody is positive, and the copy number of HCV RNA is higher than the normal upper limit of the detection value;
• There is a history of COVID-19 vaccination within one month before the first administration of this test, and there is a history of other vaccines within three months before the first administration of this test;
• Subjects who are known to be allergic to the investigational drug or its active ingredients or excipients;
• Patients who have undergone major surgery within 4 weeks prior to the start of treatment or plan to undergo major surgery during this study period (excluding surgeries such as puncture or lymph node biopsy);
• The subject is unable to swallow, or has a history of active gastrointestinal inflammation, chronic diarrhea, known diverticulosis, or has undergone gastrectomy or gastric banding that affects drug absorption. But gastroesophageal reflux disease that has been treated with proton pump inhibitors is allowed (if there is no possibility of drug interaction);
• Subjects who took known CYP3A4 inhibitors/inducers within 14 days prior to the first administration (see Appendix 7 for details);
• History of having T-cell lymphoblastic lymphoma (T-LBL) or T-cell lymphoblastic leukemia (T-ALL);
• Any history of malignant myeloid tumors, including myelodysplastic syndrome (MDS), or abnormal detection indicators related to MDS or myeloproliferative tumors (MPN);
• Individuals with a history of abuse or drug use of psychotropic substances;

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (1)

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, China

Location

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Qiu Lugui

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• QI Junyuan

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

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: August 14, 2024
• First Posted: August 16, 2024
• Study Start: August 3, 2021
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: January 12, 2026

Record last verified: 2024-08

Locations

CN (1)