Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HLX97 (a KAT6A/B Inhibitor) in Patients With Advanced/Metastatic Solid Tumor

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HLX97 (KAT6A/B Small Molecule Inhibitor) in Patients With Advanced/Metastatic Solid Tumor

This study is an open-label, multicenter Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of HLX97 ( KAT6A/B inhibitor) in patients with advanced/metastatic solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Drug: HLX97; Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhixin Yu; Phone Number: 021-22200000; Email: zhixin_yu@henlius.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects must voluntarily agree to participate in the trial and sign a written informed consent form;
• 18-80 years of age, either sex;

• Subjects who meet the corresponding requirements below will be enrolled.

  1. Part 1A will enroll subjects with histologically or cytologically confirmed advanced/metastatic HR-positive, HER2-negative breast cancer (BC), castration-resistant prostate cancer (CRPC), or non-small cell lung cancer (NSCLC) who have failed standard therapy or for whom no standard therapy exists.
  2. Part 1B will enroll subjects with histologically or cytologically confirmed advanced or metastatic HR-positive, HER2-negative breast cancer.
  3. Part 2 will enroll subjects with histologically or cytologically confirmed advanced or metastatic HR-positive, HER2-negative breast cancer.
• ECOG performance status of 0-1;
• Life expectancy ≥ 12 weeks;
• Adequate bone marrow and organ function.

Exclusion Criteria:

• History of any second malignancy within 3 years prior to signing the ICF. Exceptions include early-stage malignancies (carcinoma in situ or Stage I tumors) that have been curatively treated, such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, or papillary thyroid cancer.

Active systemic infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose.

Subjects with poorly controlled clinical symptoms or diseases of the cardiovascular and cerebrovascular system, including but not limited to:

NYHA Class ≥II heart failure or left ventricular ejection fraction (LVEF) < 50%; Unstable angina; Myocardial infarction or cerebrovascular accident within 6 months (excluding lacunar infarction, minor cerebral ischemia, or transient ischemic attack); Poorly controlled arrhythmias (including QTc interval ≥450 ms for males or ≥470 ms for females, calculated using the Fridericia formula); Poorly controlled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg despite active treatment).

Presence of spinal cord compression or clinically symptomatic central nervous system (CNS) metastases, defined as untreated, symptomatic, or requiring corticosteroids or anticonvulsants to control symptoms. Subjects with stable brain metastases may be included. Subjects with previously diagnosed brain metastases are eligible if they have completed treatment, have recovered from the acute effects of radiotherapy or surgery prior to enrollment, have discontinued corticosteroid therapy for these metastases for at least 3 weeks, and are neurologically stable for 2 months (requiring MRI confirmation).

Presence of residual toxicity from prior anti-tumor therapy that has not resolved, defined as toxicity not resolved to Grade ≤1 or baseline levels per CTCAE V5.0 (alopecia excepted).

Note: Subjects with chronic, stable Grade 2 toxicity deemed by the investigator to be related to prior anti-tumor therapy (defined as no worsening to ≥ Grade 2 for at least 3 months prior to enrollment and managed with standard medical measures) may be enrolled; for example: chemotherapy-induced neuropathy, fatigue, and residual toxicity from prior immunotherapy (Grade 1 or 2 endocrinopathies, which may include hypothyroidism/hyperthyroidism, Type 1 diabetes mellitus, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation/vitiligo).

Prior radiotherapy to bone marrow involving >25% of the total bone marrow volume (e.g., prior whole pelvic radiotherapy, whole spine radiotherapy, etc.; excluding local radiotherapy to single or a few vertebral bodies, local radiotherapy to the chest wall, etc.).

Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (defined as requiring drainage at least once monthly).

Use of therapeutic anticoagulants. Low molecular weight heparin is permitted. Use of vitamin K antagonists or Factor Xa inhibitors may be permitted after discussion with the sponsor.

Active inflammatory gastrointestinal disease, refractory or unresolved chronic diarrhea, or history of gastrectomy, gastric banding surgery, or other gastrointestinal conditions or surgeries that could significantly alter the absorption of HLX97 tablets. Treated gastroesophageal reflux disease is permitted.

Patients who received systemic corticosteroids (prednisone ≥10 mg/day or equivalent dose of similar medication) or other immunosuppressive agents within 14 days prior to the first dose.

etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation（Single）; A total of 5 dose escalations were preset: Dose1, Dose2, Dose3, Dose4, Dose5	Drug: HLX97; HLX 97 will be taken as an oral medication.
Experimental: Dose Escalation（in combination with Fulv）; A total of 3 dose escalations were preset: Dose1, Dose2, Dose3	Drug: HLX97; HLX 97 will be taken as an oral medication.; Drug: Fulvestrant; Fulvestrant will be taken as an intramuscular medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 28 days after the first administration of HLX97.	From first dose to the end of Cycle 1 (each cycle is 4 weeks)
MTD	the highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX97	From first dose to the end of Cycle 1 (each cycle is 4 weeks)
ORR	Percentage of participants with complete response (CR) and partial response (PR) based on investigator assessment.	approximately up to 24 months
PFS	The PFS is defined as the time from the date of enrollment to the date of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause,whichever occurred first.	approximately up to 24 months.

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: HLX97-FIH101

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