A Study of XS-04 in Patients with Relapsed or Refractory Hematologic Malignancies

NCT06820268 | Recruiting Phase 1

• 1 other identifier: XS-04-I101
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 4

Brief Summary

Evaluation of the safety, tolerability, pharmacokinetics, and preliminary efficacy of XS-04 in patients with relapsed or refractory hematologic malignancies

Conditions

B-cell Lymphoma; Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• The occurrence of treatment-related adverse events meeting the criteria for dose limiting toxicities (DLTs)

  Safety indicators

  At the end of C1D21(each cycle is 28 days)

• Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D)

  Safety indicators and efficacy indicators

  Up to 24 months

Secondary Outcomes (5)

• The occurrence of adverse events (AEs) reported in all subjects who received study drug

  From enrollment up to 30 days after last dose

• The occurrence of treatment-emergent adverse events (TEAs)

  From first dose up to 30 days after last dose

• Pharmacokinetic variables including maximum plasma concentration (Cmax)

  Cycle1(28days）

• Pharmacokinetic variables including maximum plasma concentration (Cmin)

  Cycle1(28days）

• PK Parameters After Single and Multiple Oral Doses of XS-04 Tablets

  Cycle 0 to Cycle 3

Study Arms (1)

A multicenter, open-label, single-arm Phase I dose-escalation and dose-expansion clinical study

EXPERIMENTAL

For drugs, use the generic name and include dosage form, dosage, frequency, and duration. Note: Group description not yet entered.\] XS-04 tablet specifications: 0.5 mg, 5 mg, 20 mg. Dose escalation phase: 1 mg, 3 mg, 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 160 mg/day (dose adjustment allowed based on actual escalation situation); Cycle 0 phase, oral administration once (dose is half of the total daily dose for the respective dose group), observe for two days (based on the PK results of the first 1-2 dose groups, decide whether the remaining dose groups need Cycle 0 phase); thereafter Cycle 1-N phase, each 28 days is one treatment cycle, continuous administration, two times daily. Dose regimen adjustments are allowed based on PK, safety, and efficacy data in this trial. Dose expansion phase: Based on the results of the dose escalation phase, cohort one and cohort two are planned to use the RP2D dose, cohort three safety lead-in phase is

Drug: XS-04 tablet

Interventions

XS-04 tablet DRUG

Each treatment cycle is 28 days, with continuous oral administration, twice daily.

A multicenter, open-label, single-arm Phase I dose-escalation and dose-expansion clinical study

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following conditions to be enrolled:
• Voluntarily participate in the clinical trial and sign the informed consent form (ICF).
• Age ≥18 years, ≤75 years, regardless of gender.
• Dose escalation phase: Patients with mature B-cell malignant tumors confirmed by histopathology according to the 2017 World Health Organization (WHO) classification, who have failed existing treatments and have no suitable treatment options and have treatment indications.
• Dose expansion phase: Patients with B-cell lymphoma confirmed by histopathology according to the 2017 WHO classification (cohort 1 includes DLBCL patients, cohort 2 includes other B-cell lymphoma patients), and patients with myeloid tumors confirmed according to the 2016 WHO classification (cohort 3 includes AML, MDS patients).
• Meet the following disease-specific criteria (tumor types not listed below will be discussed by the sponsor and the investigators to decide if they can be enrolled):
• For indolent B-NHL (follicular lymphoma \[FL\], marginal zone lymphoma \[MZL\], and Waldenström macroglobulinemia \[WM\]), patients must have received at least two lines of systemic therapy, including at least one line of combination therapy containing anti-CD20 antibodies; for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), patients must have received at least two lines of systemic therapy, including BTK inhibitors or BCL-2 inhibitors; for MCL, patients must have received at least two lines of systemic therapy (including anti-CD20 antibodies, BTK inhibitors, etc.); for aggressive B-NHL (DLBCL), patients must have failed or relapsed after at least two lines of systemic therapy and are not suitable for hematopoietic stem cell transplantation.
• For AML, diagnosed according to the 2016 World Health Organization (WHO) classification, meeting the definition of relapsed/refractory as per the "Chinese Guidelines for the Diagnosis and Treatment of Relapsed/Refractory Acute Myeloid Leukemia (2021 Edition)";
• For MDS, pathologically confirmed MDS meeting the WHO 2016 classification criteria; and prognostic scoring system assessment as intermediate to high risk (IPSS-R score \>3), relapsed or refractory;
• B-cell lymphoma patients must have at least one radiographically measurable lesion (i.e., lymph node with long diameter \[LDi\] \>1.5 cm, extranodal lesion with LDi \>1.0 cm).
• Patients must be willing to undergo bone marrow aspiration and/or bone marrow biopsy.
• ECOG score of 0-1 for dose escalation phase; 0-2 for dose expansion phase.
• Expected survival time ≥3 months.
• For mature B-cell malignant tumors, during the screening period, there must be sufficient bone marrow not dependent on growth factor support, according to local laboratory reference ranges, as follows:
• a. Absolute neutrophil count (ANC) ≥1.0×10\^9/L (patients with neutrophils \<1.0×10\^9/L due to lymphoma bone marrow infiltration may be enrolled at the investigator's discretion); b. Platelets ≥75×10\^9/L (dose escalation phase), platelets ≥50×10\^9/L (dose expansion phase), no transfusion within 14 days before the first dose; c. Hemoglobin ≥80 g/L. For AML, white blood cell count (WBC) must be ≤20×10\^9/L (hydroxycarbamide treatment to reduce white blood cells is allowed).

You may not qualify if:

• Patients meeting any of the following conditions are not eligible for this clinical study:
• Burkitt lymphoma/leukemia, plasma cell myeloma, plasmablastic lymphoma.
• Acute promyelocytic leukemia (APL) or BCR-ABL positive AML patients or those with a history of myeloproliferative neoplasms (MPN).
• Use of other cytotoxic drugs, investigational drugs, or other antitumor drugs within 14 days or 5 half-lives before the first dose of the study drug (whichever is shorter) (except hydroxycarbamide and leukapheresis). Patients who received tumor immunotherapy, antibody, or peptide antitumor drug treatment within 4 weeks before the first dose of the study drug.
• Patients who underwent therapeutic surgery other than diagnostic, biopsy, or drainage procedures within 4 weeks before the first dose of the study drug, or who are expected to undergo major surgery during the study. For patients who underwent drainage procedures (e.g., thoracic, biliary, etc.) and/or placement of drainage tubes within 4 weeks before the study drug, related symptoms/signs must have substantially resolved, and no prophylactic/therapeutic use of antibiotics is required.
• Systemic radiotherapy within 4 weeks before the first dose of the study drug.
• Unresolved toxic reactions from previous antitumor treatments (\> NCI-CTCAE 5.0 grade 1), alopecia, pigmentation, neurotoxicity, or other toxicities assessed by the investigator as chronic and not affecting the safety of the study drug, resolved to NCI-CTCAE 5.0 grade 2 or below are allowed for enrollment.
• Previous allogeneic stem cell transplantation; autologous stem cell transplantation or adoptive immune cell therapy within 3 months before the first dose of the study drug (mature B-cell malignant tumor patients) or within 6 months (AML, MDS patients).
• Patients with lymphoma/leukemia involving the central nervous system (CNS).
• Dysphagia, or a history of severe gastrointestinal disease (e.g., active inflammatory bowel disease, gastrointestinal perforation) with symptoms that cannot be reasonably controlled; or gastrointestinal diseases affecting drug absorption (e.g., Crohn's disease, ulcerative colitis, ileus, short bowel syndrome) or other malabsorption conditions.
• Patients with ocular conjunctival, corneal lesions (can be enrolled after treatment of ocular lesions is cured).
• Patients with active or unstable cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities requiring clinical intervention;
• Acute coronary syndrome, congestive heart failure, myocardial infarction, unstable angina, coronary/peripheral artery bypass grafting, cerebral infarction, cerebral hemorrhage, pulmonary embolism, deep vein thrombosis (within 3 months before the first dose) or other severe cardiovascular events within 6 months before the first dose;
• New York Heart Association (NYHA) heart function classification ≥II;

Sponsors & Collaborators

• NovaOnco Therapeutics Co., Ltd.: lead

Study Sites (4)

Beijing Cancer Hospital

Beijing, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangdong, China

NOT YET RECRUITING

Affiliated Hospital of Hebei University

Hebei, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Hubei, China

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Bone Marrow Diseases

Central Study Contacts

Jun Zhu, MD

CONTACT

88196922; zhujun3346@163.com

Yuqin Song, MD

CONTACT

88196922; SongYQ_VIP@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A multicenter, open-label, single-arm Phase I dose-escalation and dose-expansion clinical study

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: February 11, 2025
• Study Start: January 14, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): March 15, 2028
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)