To Evaluate XNW5004 Tablets in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma

A Phase II Clinical Study of XNW5004 Tablets in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma

This is an open-label, multi-center clinical study to evaluate the efficacy and safety of XNW5004 tablets in subjects with R/R PTCL. The study plans to enroll approximately 50 subjects.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: XNW5004 tablets

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiming Li M.D.; Phone Number: 13719189172; Email: lizhm@sysucc.org.cn
• Study Contact Backup: Name: Hui Zhou M.D.; Phone Number: 13975879796; Email: zhouhui@hnca.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18-70 years (inclusive)，gender not limited.
• Pathologically diagnosed, relapsed or refractory peripheral T-cell lymphoma.
• Disease status defined as relapsed or refractory after >=2 prior systemic treatment lines, including at least one new drug; subjects with CD30 positive ALCL requires prior treatment with Brentuximab vedotin.
• Subjects who have received prior radiotherapy are allowed to enroll, but radiotherapy alone is not considered a systemic therapy.
• Having at least one measurable lesion for evaluation.
• Agree to provide archived tumor tissue samples or fresh tumor tissue samples that meet the requirements.
• Life expectancy of at least 12 weeks.
• Subjects must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Have adequate organ function as defined in the following requirements.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.Non-sterile subjects must be willing to use a highly effective contraception (e.g., IUD, pill, or condom) for the duration of the study and for 6 months after the last dose of study drug unless their partner is sterilized. For male subjects whose partner is a woman of childbearing potential, surgical sterilization or agreement to use effective contraception for the duration of the study and for 6 months after the last dose of study drug is required. In addition, males must agree not to donate sperm during the study participation and for at least 6 months after the last dose of study drug.
• Able to provide written informed consent form prior to the commencement of any study activity/procedure.

Exclusion Criteria:

• Prior exposure to EZH2 inhibitor(s) or EZH1/2 inhibitor(s);
• Subjects with known hypersensitivity to the study drug or its active ingredients or excipients.
• Subjects who have received anti-tumor therapy, such as chemotherapy, immunotherapy, radiotherapy, and targeted therapy, within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of the study drug, received CAR-T therapy within 12 weeks prior to the first dose of the study drug, autologous hematopoietic stem cell transplantation (Auto-HSCT) within 3 months prior to the first dose of the study drug.
• Subjects who have received other anti-tumor investigational drug treatment within 28 days prior to the first dose of XNW5004 in this study.
• Subjects who have undergone major surgery within 4 weeks prior to the start of study treatment or who intend to undergo major surgery during this study (except for procedures such as puncture or lymph node biopsy).
• Subjects who have an allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
• Subjects who have received systemic treatment with corticosteroids (prednisone at a dose of > 10 mg per day or equivalent doses of other glucocorticoids) or other immunosuppressive drugs within 14 days prior to the use of the study drug. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal replacement therapy with prednisone at a dose of ≤ 10 mg per day or equivalent doses of other glucocorticoids are permitted.
• Subjects taking known strong CYP3A4 inhibitors/inducers and P-glycoprotein (P-gp) inhibitors within 14 days prior to the first dose.
• Subjects who have received live virus vaccines (including live attenuated vaccines) within 28 days prior to dosing. Inactivated vaccines are permitted.
• Subjects with a history of psychotropic drug abuse or drug abuse.
• Subjects who have received anti-tumor therapy in the early stage and have not recovered from toxicity (toxicity has not recovered to ≤ Grade 1 according to NCI-CTCAE 5.0). Except for other toxicities (such as alopecia, etc.) that do not affect the safety evaluation of subjects in the opinion of the investigator.
• Subjects with history of other malignancies within 3 years prior to enrollment and not meeting clinical cure criteria. Exceptions are the following: cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, intraductal carcinoma in situ of the breast, and papillary carcinoma of the thyroid that can be treated locally.
• Subjects with mycosis fungoides, Sézary syndrome, or primary cutaneous T-cell lymphoma.
• Subjects with previous or current central nervous system invasion.
• Subjects with previous or current testicular or breast invasion.
• Subjects with previous or current hemophagocytic syndrome.
• Subjects with previous or current primary or secondary hematologic diseases that may affect bone marrow function in addition to primary malignancies, such as immune thrombocytopenia, autoimmune hemolytic anemia, aplastic anemia, etc.
• Subjects with previous or current acute myeloid leukemia (AML).
• Subjects with previous or current T-cell lymphoblastic lymphoma (T-LBL) or T-lymphoblastic leukemia.
• Subjects who have any history of myeloid malignancy, including myelodysplastic syndrome (MDS), or abnormal tests results of markers related to MDS or myeloproliferative neoplasm (MPN).
• Subjects who previously hadcentral nervous system lesions, or diseases accompanies with central nervous system lesions, including but not limited to, epilepsy, paralysis, stroke, severe brain injury, Alzheimer's disease, Parkinson's disease, cerebellar disease, cerebral organic syndrome, or psychosis, etc.
• Subjects with clinically significant cardiovascular disease;
• Tumor invasion of important peripheral organs and blood vessels (such as heart and pericardium, trachea, esophagus, aorta, superior vena cava, etc.) posing a risk of bleeding or the risk of esophageal tracheal fistula or esophageal pleural fistula.
• Subjects with clinically symptomatic thoracoabdominal effusion or pericardial effusion that are poorly controlled after repeated treatment.
• Subjects with unexplained fever and body temperature>38.0 ℃.
• Subjects who have severe active systemic infection.
• Subjects with a history of tuberculosis infection within one year prior to enrollment, or with a history of active tuberculosis infection more than one year ago without sufficient anti tuberculosis treatment.
• A known history of HIV infection or acquired immunodeficiency syndrome (AIDS), or Anti- Treponema Pallidum test (anti-TP) positive.
• Subjects who are HBsAg positive and have HBV-DNA copy numbers higher than the lower normal limit of the detection value, or subjects who are anti HBc positive and have HBV-DNA copy numbers higher than the lower normal limit of the detection value. Subjects with HCV antibody positive and HCV-RNA copy number higher than the lower normal limit of the detection value.
• Subjects with difficulties to swallow the study drug or conditions that significantly affect gastrointestinal function, such as malabsorption syndrome, gastrectomy or small bowel resection, clinically symptomatic inflammatory bowel disease, or incomplete/complete intestinal obstruction.
• Subjects who are unable to swallow or has a history of active gastrointestinal inflammation, chronic diarrhea, known diverticular disease, or has undergone gastrectomy or gastric banding that affects drug absorption. But gastroesophageal reflux that has been treated with proton pump inhibitors is allowed (if there is no possibility of drug interaction).
• Subjects with conditions known to have bleeding tendencies, such as von Willebrand disease or hemophilia.
• Subjects who are pregnant or breastfeeding, or expects to conceive within the projected duration of the study.
• Subject who may not be able to complete this study for other reasons or who, in the opinion of the investigator, should not participate the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XNW5004; XNW5004 tablets Oral administration, twice daily, with a 28-day continuous dosing as one cycle.	Drug: XNW5004 tablets; XNW5004 will be administered orally as tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) assessed by independent review committee (IRC)	Percentage of participants achieving complete response (CR) and partial response (PR) in the study.	24 mounths

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR assessed by investigator	Percentage of participants achieving complete response (CR) and partial response (PR).	24 mounths
Progression free survival	time from the first dose of to the first disease progression(PD) or death	24 mounths
Time to Response	time from the first dose of XNW5004 to first CR or PR	around 4 months
Duration of response	time from the first CR or PR to the first PD or death	24 mounths
Overall survival	time from the fist dose of XNW5004 to death	around 5 years

Collaborators and Investigators

• Sponsor: Evopoint Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 25, 2024

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: XNW5004-II-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No