Phase I Study of FXS0683 in the Treatment of Blood Tumors

This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 tablets in participants with relapsed or refractory hematologic malignancies, designed to evaluate safety, tolerability, PK, and preliminary antitumor activity.The study consists of a dose-escalation phase and a dose-expansion phase. The primary objective of dose escalation is to assess safety and tolerability and to determine the MTD and/or RP2D. Dose escalation will follow an accelerated titration design combined with a Bayesian Optimal Interval (BOIN) design. The initial cohort will enroll one participant; if a treatment-related adverse event of Grade ≥2 occurs during the dose-limiting toxicity (DLT) observation period, the cohort will transition to a BOIN design and expand to include additional participants. Dose escalation may proceed in the absence of DLTs among evaluable participants.

The dose-expansion phase is intended to further evaluate safety and preliminary efficacy at selected dose level(s). Expansion may be initiated based on emerging safety, tolerability, and PK data from the dose-escalation phase without requiring completion of all escalation cohorts.

Inclusion criteria

• Voluntary participation in the clinical trial and signing of the ICF.
• Age ≥ 18 years, regardless of gender.
• Dose escalation phase: Patients with mature B-cell malignancies diagnosed per the 2017 WHO classification who have failed standard therapies and have no appropriate treatment options. Dose expansion phase: Patients with B-cell lymphoma (2017 WHO), myeloid malignancies (2022 WHO), or acute lymphoblastic leukemia.
• Dose escalation phase: Evaluable disease. Dose expansion phase: For B-cell lymphoma, at least one measurable lesion per Lugano 2014 criteria.
• Patients must be willing to undergo bone marrow aspiration and/or biopsy.
• ECOG performance status of 0-1 (dose escalation phase) or 0-2 (dose expansion phase).
• Expected survival time ≥3 months.
• Adequate bone marrow function during screening, as defined by local laboratory reference ranges, without growth factor support.
• Adequate organ function, defined by laboratory values within 7 days prior to the first dose.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception from signing the ICF until 6 months after the last dose.
• Patients at high risk of tumor lysis syndrome (TLS), defined as absolute lymphocyte count (ALC) ≥25×10⁹/L with ≥1 measurable lymph node ≥5 cm or any node ≥10 cm, must be willing to comply with TLS prophylaxis and monitoring requirements.
• Patients must be able to comply with the study procedures and visit schedule.

Exclusion criteria

• Burkitt lymphoma/leukemia, plasma cell myeloma, or plasmablastic lymphoma.
• Acute promyelocytic leukemia (APL) or BCR-ABL positive AML patients, or patients with a history of myeloproliferative neoplasms (MPN).
• Use of cytotoxic agents, investigational drugs, or other antitumor therapies within 14 days or 5 half-lives prior to the first dose; or immunotherapy, antibody-based or peptide-based therapies, or live vaccines within 4 weeks prior to the first dose.
• Patients who received any therapeutic surgery other than diagnosis, biopsy, or drainage within 4 weeks before the first dose, or patients expected to undergo major surgery during the study. Patients who underwent drainage or placement of drainage tubes within 4 weeks before the first dose must have symptoms/signs alleviated and not require prophylactic or therapeutic antibiotics.
• Patients who received systemic radiotherapy or palliative local radiotherapy within 4 weeks before the first dose.
• Toxicity from previous anticancer treatment has not recovered to ≤ grade 2, except for hair loss and pigmentation.
• Prior allogeneic stem cell transplantation; or autologous stem cell transplantation or CAR-T therapy within 3 months prior to the first dose.
• Patients with lymphoma/leukemia that has infiltrated the central nervous system.
• Patients with dysphagia or a history of severe gastrointestinal diseases and whose related symptoms cannot be reasonably controlled; or patients with gastrointestinal diseases affecting drug absorption or other malabsorption conditions.
• Active or clinically significant cardiovascular or cerebrovascular disease.
• Patients with interstitial lung disease or a history of pulmonary interstitial fibrosis; or evidence of active pneumonia found on screening chest CT scan.
• Patients with congenital immunodeficiency disorders or active autoimmune diseases, including but not limited to those with active and uncontrolled autoimmune cytopenias lasting ≥2 weeks, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
• Patients with coagulation disorders.
• Patients with a history of severe allergies or allergies to any active or inactive component of the study drug.
• Patients with uncontrolled systemic infections within 2 weeks before the first dose; hepatitis B surface antigen positive with hepatitis B virus DNA >1000 IU/ml; HCV antibody positive with HCV RNA positive; HIV antibody positive.
• Other primary malignancies within 5 years prior to enrollment, except for adequately treated basal or squamous cell skin cancer or carcinoma in situ.
• Patients who still require systemic immunosuppressive agents or systemic corticosteroids within 2 weeks before the study drug.
• Pregnant or breastfeeding women.
• Any other serious or uncontrolled acute or chronic disease or laboratory abnormality or other reasons deemed unsuitable for participation in this clinical trial by the investigator.