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

Launched by EVOPOINT BIOSCIENCES INC. · Aug 14, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called XNW5004 tablets for patients who have advanced tumors, specifically those with non-Hodgkin lymphoma that has either returned after treatment or did not respond to standard therapies. The goal is to see how well this medication works and to gather more information about its safety. The trial is currently recruiting participants aged 18 and older, including both men and women, who have been diagnosed with specific types of lymphoma and meet certain health criteria.

To be eligible, participants must have a confirmed diagnosis of relapsed or refractory lymphoma and must have had at least two previous treatment regimens without success. They should also have a life expectancy of at least 12 weeks and meet several health requirements related to their blood and organ function. Participants will receive the XNW5004 tablets and will be monitored regularly to assess their response to the treatment. Before joining, patients will need to provide informed consent and may need to undergo some tests to confirm their eligibility. It’s important to note that this trial has specific exclusion criteria, so not everyone will qualify, particularly those who have had certain previous treatments or health conditions.

Gender

ALL

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.