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

NCT07695142 | Not Yet Recruiting Phase 1

• 1 other identifier: HSK46256-101
• Study Type: interventional
• Target: 275
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor (Phase 1)

Keywords

PARP inhibitor; advanced solid tumors

Outcome Measures

Primary Outcomes (2)

• DLTs

  Incidence of dose-limiting toxicities (DLTs) at Cycle1

  Up to 24 days

• MTD

  Maximum Tolerated Dose

  Up to 24 days

Secondary Outcomes (8)

• Progression-Free Survival (PFS)

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Radiographic Progression-Free Survival (rPFS, prostate cancer only)

  Up to 24 months

• Objective Response Rate (ORR)

  Up to 24 months

Other Outcomes (1)

• Pharmacodynamic (PD) markers: PARP1 inhibition and biomarker modulation

  Circle 1 (21 days)

Study Arms (1)

HSK46256 as monotherapy

EXPERIMENTAL

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

Interventions

HSK46256 DRUG

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.

HSK46256 as monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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;

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 10, 2026
• Study Start: July 9, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)