Trial Title:
To Evaluate a Phase I/II Clinical Study of XNW5004 Tablets in Patients With Relapsed/Refractory Advanced Tumors
NCT ID:
NCT06558513
Condition:
Advanced Tumor
Lymphoma
Conditions: Keywords:
EZH2 inhibitor
XNW5004
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
XNW5004 tablets
Description:
XNW5004 an EZH2 inhibitor, BID, administered in continuous
Arm group label:
XNW5004
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
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- Only limited to stage IIa, pathologically diagnosed, relapsed or refractory
follicular lymphoma, peripheral T-cell lymphoma, and diffuse large B-cell lymphoma,
with recurrence and refractory defined according to inclusion criteria 2: Cohort 1:
Follicular lymphoma (EZH2 mutant): Subjects whose genetic testing results showed the
presence of EZH2 gene mutations; If the subject is unable to provide previous
genetic testing results or there is no EZH2 gene mutation information in the
previous genetic testing results, tumor tissue samples or bone marrow samples (only
for subjects with bone marrow invasion) and blood samples must be provided. Only
after confirming the presence of EZH2 gene mutations in the central laboratory can
they be included in this queue; Cohort 2: Follicular lymphoma (EZH2 wild-type):
subjects whose genetic testing results showed no EZH2 gene mutations; If the subject
is unable to provide previous genetic testing results or there is no EZH2 gene
mutation information in the previous genetic testing results, tumor tissue samples
or bone marrow samples (only for subjects with bone marrow invasion) and blood
samples must be provided. Only after confirmation by the central laboratory that
there is no EZH2 gene mutation can they be included in this queue; Cohort 3:
Peripheral T-cell lymphoma, according to the 2016 WHO classification of lymphoid
tissue tumors; Cohort 4: Diffuse large B-cell lymphoma;
- At least one measurable lesion should be used as the evaluation basis
- During the dose escalation phase, subjects should provide tumor tissue samples or
bone marrow samples (limited to subjects with bone marrow invasion) and oral swabs
(control samples) as much as possible. If tumor tissue or bone marrow samples cannot
be provided, they can be included in the study after evaluation by the researcher,
provided that they meet other inclusion criteria;
- 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.
Exclusion Criteria:
- 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;
- It is known that the subjects have bleeding prone diseases such as von Willebrand's
disease or hemophilia, or require long-term treatment with warfarin or other vitamin
K antagonists (such as phenylpropanoid coumarin);
- Individuals who may not be able to complete this study due to other reasons or whom
the researcher believes should not be included.
- Previously suffering from or accompanied by central nervous system disorders,
including but not limited to: epilepsy, paralysis, stroke, severe brain injury,
senile dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,
mental illness, etc;
- The presence of central nervous system or testicular invasion;
- Stage IIa only: follicular lymphoma grade 3b, mixed histology, or follicular
lymphoma histologically transformed into diffuse large B-cell lymphoma;
- Stage IIa only: Diffuse large B-cell lymphoma diagnosed by FISH testing with MYC,
BCL-2, and/or BCL-6 rearrangement;
- Stage IIa only: mycosis fungoides, S é zary syndrome, and primary cutaneous enlarged
T-cell lymphoma;
- Burkitt's lymphoma, a gray area lymphoma between diffuse large B-cell lymphoma and
Burkitt's lymphoma, and a gray area lymphoma between diffuse large B-cell lymphoma
and Hodgkin's lymphoma;
- Previously received organ transplantation or allogeneic hematopoietic stem cell
transplantation (ALLo HSCT);
- Auto-HSCT (autologous hematopoietic stem cell transplantation) was performed within
3 months prior to administration in this experiment;
- Immunosuppressants are being used, including but not limited to: cyclosporine,
tacrolimus, etc. used within 2 weeks prior to administration in this trial; Within 7
days before administration, receive high-dose corticosteroids (prednisone with a
daily dose greater than 10mg or equivalent doses of other corticosteroids);
- Received radiotherapy within 4 weeks prior to administration in this trial;
- Received anti-tumor treatments such as chemotherapy, targeted therapy, and
anti-tumor traditional Chinese medicine within 4 weeks prior to administration in
this trial;
- Received immunotherapy within 4 weeks prior to administration in this trial;
- Received CAR-T treatment within 12 weeks prior to administration in this trial;
- Those who have used any other clinical trial drugs within 4 weeks prior to the
administration of this trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hematology Hospital, Chinese Academy of Medical Sciences
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Contact:
Last name:
Qiu Lugui
Investigator:
Last name:
QI Junyun
Email:
Principal Investigator
Start date:
July 5, 2021
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Evopoint Biosciences Inc.
Agency class:
Industry
Collaborator:
Agency:
Shanghai Dingyue Biotechnology Co., LTD
Agency class:
Other
Collaborator:
Agency:
Beijing Jiyingjia Medical Laboratory Co.,Ltd.
Agency class:
Other
Collaborator:
Agency:
Shanghai Jinghan Biological Technology Co., Ltd.
Agency class:
Other
Source:
Evopoint Biosciences Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06558513
