Phase I Study of FXS0683 in the Treatment of Blood Tumors (FXS0683-001)

A Multicenter, Open, Single-arm Phase I Dose-escalation and Dose-expansion Clinical Study: Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of FXS0683 Tablets in Patients With Relapsed or Refractory Hematologic Malignancies.

This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 in participants with relapsed or refractory hematologic malignancies to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia; B-Cell Lymphoma
• Intervention / Treatment: Biological: FXS0683

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lugui Qiu; Phone Number: 86 022-23608108; Email: qiulg@ihcams.ac.cn
• Study Contact Backup: Name: Bo Jiang; Phone Number: 86 022-23608381; Email: jiangbo@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 301600
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS)
      • Contact: Shuo Chen; Phone Number: 86 022-23608381; Email: gcp@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary participation in the clinical trial and signing of the ICF.
2. Age ≥ 18 years, regardless of gender.
3. 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.
4. Dose escalation phase: Evaluable disease. Dose expansion phase: For B-cell lymphoma, at least one measurable lesion per Lugano 2014 criteria.
5. Patients must be willing to undergo bone marrow aspiration and/or biopsy.
6. ECOG performance status of 0-1 (dose escalation phase) or 0-2 (dose expansion phase).
7. Expected survival time ≥3 months.
8. Adequate bone marrow function during screening, as defined by local laboratory reference ranges, without growth factor support.
9. Adequate organ function, defined by laboratory values within 7 days prior to the first dose.
10. 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.
11. 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.
12. Patients must be able to comply with the study procedures and visit schedule.

Exclusion Criteria:

1. Burkitt lymphoma/leukemia, plasma cell myeloma, or plasmablastic lymphoma.
2. Acute promyelocytic leukemia (APL) or BCR-ABL positive AML patients, or patients with a history of myeloproliferative neoplasms (MPN).
3. 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.
4. 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.
5. Patients who received systemic radiotherapy or palliative local radiotherapy within 4 weeks before the first dose.
6. Toxicity from previous anticancer treatment has not recovered to ≤ grade 2, except for hair loss and pigmentation.
7. Prior allogeneic stem cell transplantation; or autologous stem cell transplantation or CAR-T therapy within 3 months prior to the first dose.
8. Patients with lymphoma/leukemia that has infiltrated the central nervous system.
9. 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.
10. Active or clinically significant cardiovascular or cerebrovascular disease.
11. Patients with interstitial lung disease or a history of pulmonary interstitial fibrosis; or evidence of active pneumonia found on screening chest CT scan.
12. 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.
13. Patients with coagulation disorders.
14. Patients with a history of severe allergies or allergies to any active or inactive component of the study drug.
15. 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.
16. Other primary malignancies within 5 years prior to enrollment, except for adequately treated basal or squamous cell skin cancer or carcinoma in situ.
17. Patients who still require systemic immunosuppressive agents or systemic corticosteroids within 2 weeks before the study drug.
18. Pregnant or breastfeeding women.
19. 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.

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: FXS0683; This is a first-in-human, multicenter, open-label, single-arm Phase I study consisting of dose-escalation and dose-expansion phases. FXS0683 will be administered orally once daily at assigned dose levels in 28-day cycles.	Biological: FXS0683; FXS0683 is a potent and highly selective BCL-2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with DLTs	A DLT is defined as any adverse event or laboratory abnormality occurring during the DLT observation period that is assessed as at least possibly related to FXS0683 and meets pre-specified DLT criteria, graded per NCI-CTCAE Version 6.0.	At the end of Cycle 1 (each cycle is 28 days).
MTD and/or RP2D	The MTD and/or RP2D will be determined based on the overall assessment of safety, tolerability, PK, and preliminary efficacy data.	Up to approximately 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events and Clinically Significant Safety Findings	Adverse events (AEs) will be summarized, and severity will be graded according to NCI-CTCAE Version 6.0.	From first dose of study drug until 30 days after the last dose.
Objective Response Rate (ORR) Of FXS0683 Monotherapy	ORR will be assessed according to disease-specific response criteria (e.g., Lugano 2014, iwCLL 2018, ELN 2022, or IWG 2006), as applicable.	Up to approximately 3 years.

Collaborators and Investigators

• Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 7, 2028
• Study Completion (Estimated): August 8, 2029

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
• Other Study ID Numbers: FXS0683-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No