A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of HSK46256 in Patients With Advanced Solid Tumors

A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of HSK46256 Tablets in Patients With Advanced Solid Tumors

This is a Phase 1, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HSK46256 tablets, a selective PARP1 inhibitor, in patients with advanced solid tumors. The study consists of a dose escalation phase and a dose expansion phase. In the dose escalation phase, a 3+3 dose escalation design will be used to evaluate multiple dose levels. The dose expansion phase will enroll patients into expansion cohorts at selected dose levels to further evaluate safety and preliminary efficacy.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor (Phase 1)
• Intervention / Treatment: Drug: HSK46256

• Study Type: Interventional
• Enrollment (Estimated): 275
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Jian Zhang, MD; Phone Number: +86 18017312991; Email: syner2000@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years, voluntarily participate and provide signed informed consent,
• ECOG performance status 0-1 or KPS >60; estimated life expectancy ≥12 weeks,
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors, failed prior standard therapy, intolerant to standard therapy, or no available standard therapy,
• Dose escalation: prior treatment with one line of non-selective PARP inhibitor allowed,
• Documented HRR gene mutation,
• Agree to provide tumor tissue and/or blood samples,
• Fertile participants must agree to use effective contraception during study and for 3 months after last dose; negative pregnancy test for females,

Exclusion Criteria:

• Other malignancies within past 2 years (except adequately treated basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma);
• Uncontrolled moderate to large pleural, pericardial, or peritoneal effusions;
• Prior anticancer therapy or concomitant use of CYP3A4 strong/moderate inhibitors/inducers within protocol-specified washout periods;
• Prior anticancer treatment toxicity not resolved to CTCAE ≤Grade 1 (except alopecia, skin toxicity);
• Any condition affecting drug swallowing or significantly impacting drug absorption/PK;
• Severe or uncontrolled cardiac disease (QTcF prolongation, significant arrhythmia, LVEF <50%, recent MI/heart failure);
• Arterial/venous thromboembolic events within 6 months deemed uncontrolled risk;
• Severe/uncontrolled diabetes, hypertension, active bleeding, epilepsy, COPD, interstitial lung disease, active systemic infection;
• Unstable systemic disease (severe hepatic/renal/metabolic disorders);
• Prior MDS or AML diagnosis, or history of hematopoietic stem cell transplantation;
• Major surgery or severe trauma within 4 weeks;
• HIV positive, active hepatitis B/C, or active syphilis;
• Known hypersensitivity to study drug or excipients;
• Participation in another interventional trial within 4 weeks;
• Pregnant or lactating women;

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: HSK46256 as monotherapy; Drug: HSK46256 Administration: Oral tablet, once daily (except during the single-dose period) Regimen: Single-agent, dose-escalation Duration: Until disease progression or treatment discontinuation	Drug: HSK46256; Oral administration. Dose escalation: an initial single-dose period followed by multiple-dose cycles until disease progression or intolerable toxicity. Dose expansion: multiple-dose cycles directly. Specific dose levels and dosing frequency will be determined based on dose-escalation data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLTs	Incidence of dose-limiting toxicities (DLTs) at Cycle1	Up to 24 days
MTD	Maximum Tolerated Dose	Up to 24 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)		Up to 24 months
Disease Control Rate (DCR)		Up to 24 months
Progression-Free Survival (PFS)		Up to 24 months
Radiographic Progression-Free Survival (rPFS, prostate cancer only)		Up to 24 months
Objective Response Rate (ORR)	Complete response + Partial response (CR+PR) based on RECIST 1.1.	Up to 24 months
PK parameters of HSK46256	Peak plasma concentration (Cmax)	Circle 1 (21 days)
Pharmacokinetic parameters of HSK46256	Area Under the Plasma Concentration-Time Curve (AUC)	Circle 1 (21 days)
Pharmacokinetic parameters of HSK46256	Half-life (T1/2)	Circle 1 (21 days)

Other Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamic (PD) markers: PARP1 inhibition and biomarker modulation	Circle 1 (21 days)

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 9, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: July 5, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: PARP inhibitor; advanced solid tumors
• Other Study ID Numbers: HSK46256-101

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