Phase I Study of FXS887 in the Treatment of Solid Tumors (FXS887-I101)

A Single-Arm, Open-Label, Dose-Escalation and Expansion Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FXS887 in Patients With Advanced Solid Tumors

This is a single-arm, open-label, dose-escalation and dose-expansion Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of FXS887 in patients with advanced solid tumors. FXS887 is a innovative ATR inhibitors of a class of small-molecule inhibitors targeting ATR kinase.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor Refractory to Conventional Treatment
• Intervention / Treatment: Drug: FXS887

Detailed Description

There will be two parts for this study:

Phase 1a is a dose-escalation, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of FXS887 in patients with advanced solid tumors. Approximately 14 subjects are expected to be enrolled.

Dose escalation will adopt a combination of "accelerated titration" and "3+3" design. The initial 2 dose cohorts will use the accelerated titration, while the 3+3 design will be implemented starting in other dose cohorts. If a Dose Limiting Toxicity (DLT) event or a study treatment-related adverse event of grade ≥2 occurs during the DLT observation period, the current dose cohort will switch to the 3+3 design. Eligible subjects will receive oral FXS887 once daily. The DLT observation period is within 28 days after the first dose (Cycle 1), followed by multiple-dose studies in Cycle 2 and subsequent cycles. Treatment will continue until the subject experiences disease progression, death, unacceptable toxicity, withdrawal of informed consent, or other reasons requiring discontinuation of study treatment (whichever occurs first).

Phase 1b is an open-label, dose-expansion study that plans to enroll eligible patients with advanced solid tumors. The sample size will be determined based on the results of the Phase 1a, to further evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of FXS887 at the recommended expansion dose(s).

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaohua Wu; Phone Number: 81000 +86 21 6417 5590; Email: wu.xh@fudan.edu.cn
• Study Contact Backup: Name: Jian Zhang; Phone Number: 86 21 6417 5590; Email: syner2000@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Che Li; Phone Number: 86 21 3819 6379; Email: junqian@fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged ≥ 18 years, male or female;
2. Participants must fully understand the requirements of the study and voluntarily sign the written informed consent;
3. Participants with histologically/cytologically confirmed advanced solid tumors who have received ≥ 1 line of systemic therapy prior to enrollment in the study and experienced failure of standard therapy (disease progression or intolerance);
4. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, participants must have at least one measurable target lesion;
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
6. Estimated life expectancy of ≥ 12 weeks;
7. Participants must have adequate organ and bone marrow function.
8. For female participants of childbearing age, the serum pregnancy test within 7 days prior to the first dose of the study drug must be negative; eligible participants of reproductive potential (both males and females) must agree to use reliable contraceptive methods (hormonal, barrier, abstinence, etc.) with their partners during the study period and for at least 6 months after the last dose of the study drug.

Exclusion Criteria:

1. Within the washout period of prior anti-tumor medication treatment (4 weeks or 5 half-lives after the last dose, whichever is longer) prior to the first dose of FXS887;
2. Have participated in another clinical study within 4 weeks prior to the first dose of FXS887;
3. Have a history of hypersensitivity to any known components of FXS887 or its analogues;
4. Have intolerance to ATR inhibitors or have received ATR inhibitors within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of FXS887;
5. Need to take strong CYP3A inhibitors and/or inducers, as well as P-gp (P-glycoprotein) inhibitors and/or inducers within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of FXS887 and during the study period;
6. Need to take drugs known to prolong the QTc interval during the study period;
7. Have had other malignant tumors within 2 years prior to the first dose of FXS887, except for local tumors that have been cured and judged by the investigator to have a low risk of recurrence;
8. Have received radiation therapy within 14 days prior to the first dose of FXS887;
9. Have not recovered from adverse events caused by prior anti-cancer treatment (recovered to Grade 1 or baseline), except for alopecia, pigmentation of any grade, Grade ≤2 peripheral sensory neuropathy, and items explicitly specified in the inclusion criteria;
10. Have refractory nausea and vomiting, chronic gastrointestinal diseases including but not limited to active diverticulitis and symptomatic peptic ulcers, inability to swallow oral medications, or a history of extensive small bowel resection or other conditions that significantly impair gastrointestinal absorption as judged by the investigator;
11. Have undergone major surgery within 2 weeks prior to the first dose or have not recovered from surgical complications;
12. Have primary central nervous system (CNS) tumors, meningeal metastasis, spinal cord compression, or brainstem metastasis; participants with known untreated brain metastases or symptomatic or unstable disease are excluded; participants who have completed treatment for brain metastases (radiation therapy or surgery) with stable metastases and no relevant symptoms (without medication control) within 4 weeks prior to the first dose may be enrolled;
13. Have severe cardiovascular diseases;
14. Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage and medical intervention;
15. Have active infections requiring treatment (e.g., participants are receiving anti-infective treatment) within 14 days prior to the first dose of FXS887, including Hepatitis C virus (HCV), Human Immunodeficiency Virus (HIV), uncontrolled active Hepatitis B virus (HBV) infection, syphilis infection, known active tuberculosis, etc.

16. Known infection with hepatitis B virus (HBV) or hepatitis C virus (HCV):

    • participants with controlled HBV infection (serum HBV-DNA < 500 IU/mL or < 2,000 copies/mL) are allowed to enroll in this study.
    • participants who are HCV antibody-positive with controlled infection [polymerase chain reaction (PCR) for serum HCV-RNA below the lower limit of detection] are allowed to enroll in this study.
17. History of human immunodeficiency virus (HIV) infection;
18. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy, or clinically active ILD;
19. Known substance abuse or psychiatric disorder that may interfere with compliance with study requirements;
20. Participants are pregnant, breastfeeding, or planning to become pregnant during the study period;
21. Investigator considers the participant has other factors that may affect study results or interfere with participation in the entire study, including past or existing medical conditions, treatment or laboratory abnormalities, or unwillingness to comply with study procedures, restrictions, and requirements-any condition deemed unsuitable for enrollment 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: FXS887; This is a single-arm, open-label, dose-escalation and dose-expansion Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of FXS887 in patients with advanced solid tumors. It mainly consists of two parts: the Phase Ia dose-escalation study and the Phase Ib dose-expansion study. Participants will receive FXS887 orally once-daily at determined dose levels on a 28-day cycle.

Drug: FXS887; FXS887 is an innovative ATR inhibitor targeting ATR kinase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with DLTs	DLTs will be assessed during the dose-escalation phase and are defined as toxicities that meet pre-defined DLT criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (28 days) of treatment.	Up to Day 28
Maximum tolerated dose (MTD) or Maximum administered dose(MAD)	The MTD is defined as the highest dose level at which the proportion of subjects who experience Dose-Limiting Toxicity (DLT) is less than 1/3 during the DLT observation period. If the MTD is not established after the completion of the dose-escalation, the highest safe dose level will be defined as the MAD.	Up to 12 Months
Incidence of Treatment-Emergent Adverse Events (TEAEs)[Safety and Tolerability]	Number and frequency of subjects with adverse events, including changes in vital signs, electrocardiograms (ECGs), physical examinations, and laboratory parameters, graded according to NCI CTCAE v5.0.	From first dose of study drug until 30 days after the last dose.
Phase 1a: recommended phase 2 dose (RP2D)	The RP2D (Recommended Phase 2 Dose) determined based on comprehensive consideration of safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics), and efficacy data.	Up to 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of FXS887	Maximum observed plasma concentration of FXS887 following single and multiple doses.	From the day of first dose to 30 days after last dose of FXS887
Area under the plasma concentration-time curve (AUC)of FXS887	The area under the plasma concentration-time curve of FXS887 following single and multiple doses.	From the day of first dose to 30 days after last dose of FXS887
Time to reach maximum plasma concentration (Tmax) of FXS887	Time to reach maximum plasma concentration of FXS887 following single and multiple doses.	From the day of first dose to 30 days after last dose of FXS887
Elimination Half-Life (t1/2) of FXS887	Apparent terminal elimination half-life of FXS887 in plasma.	From the day of first dose to 30 days after last dose of FXS887
Objective response rate, ORR	Antitumor activity by evaluation of tumor response assessments based on RECIST 1.1	From first dose of study drug until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Progression Free Survival	Antitumor activity by evaluation of tumor response assessments based on RECIST 1.1	From first dose of study drug until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): January 5, 2026
• Primary Completion (Estimated): April 28, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: FXS887-I101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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