A Phase I, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of HSK42360 in Patients With BRAF V600 Mutation Locally Advanced or Metastatic Solid Tumors

Haisco Pharmaceutical Group Co., Ltd.11 sites in 1 country316 target enrollmentJune 25, 2024

ConditionsSolid Tumors

InterventionsHSK42360

Overview

Phase: Phase 1
Intervention: HSK42360
Conditions: Solid Tumors
Sponsor: Haisco Pharmaceutical Group Co., Ltd.
Enrollment: 316
Locations: 11
Primary Endpoint: DLTs
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and PD of HSK42360 when given orally in patients with active BRAF V600 mutation locally advanced or metastatic Solid Tumors.

Detailed Description

The study will contain two phases: Phase Ia is dose escalation phase and Phase Ib is dose expansion phase. Phase Ia will contain two part: Dose Escalation Part (Part A) and Extension Part (Part B). Part A based on the "3+3" design for dose escalation and safety evaluation requirements. Patient cohorts at selected doses may be extended to further investigate the tolerability, PK and PD of HSK42360. The number of patients to be enrolled will be up to 10 subjects in each Part B cohort. Approximately 30-70 subjects will be enrolled in Phase Ia. Phase Ib no less than 10-50 subjects will be enrolled in each expansion cohort.

Registry

clinicaltrials.gov

Start Date

June 25, 2024

End Date

July 7, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Haisco Pharmaceutical Group Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 18 years，Male and female patients, at time of signing informed consent form (ICF).
•ECOG performance status 0-1, or KPS (Karnofsky Performance Status) Score\>
•Life expectancy ≥ 3 months.
•Patients with locally advanced or metastatic solid tumors confirmed by histology or cytology, who have failed standard treatment (disease progression after treatment or intolerable treatment); patients who have previously received BRAF and/or MEK inhibitor therapy are allowed to be included in this study.
•Positive BRAF V600 mutation result confirmed prior to the administration of HSK
•Patients will provide blood or tumor sample according to their own willingness.
•Measurable or non-measurable disease by RECIST 1.1 or RANO criteria.
•Brain metastasis patients with inactive CNS lesions; Original intracranial tumor patient with inactive CNS lesions, or patients treated with ≤4mg/day corticosteroid and without convulsion for ≥2 weeks.
•Adequate hematologic, hepatic, and renal function.
•Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose.

Exclusion Criteria

•malignant tumor within 2 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
•Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
•Treatment with any of the following:
•Prior treatment with anti-tumor drug within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK42360, whichever is shorter; Prior treatment with nitrosourea or mitomycin C within 6 weeks prior to the first dose of HSK42360; Prior treatment with palliative radiotherapy or anti-tumor herbs within 2 weeks prior to the first dose of HSK42360; Prior treatment with radiotherapy, electric field therapy, or other anti-tumor therapies within 4 weeks prior to the first dose of HSK
•Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
•Any disease which would preclude drug absorption, metabolism or pharmacokinetics, e.g. active peptic ulcer or chronic gastroesophageal reflux disease.
•Patients who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450(male)/470(female) msec; any clinically significant arrhythmia; left ventricular ejection fraction \< 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK
•Any thromboembolic events within 6 months prior to the first dose of HSK42360; any familial or acquired thrombophilia.
•Uncontrolled hypertension (systolic pressure≥160mmHg, or diastolic pressure≥100mmHg), diabetes (fasting blood-glucose≥10mmol/L), seizures, chronic obstructive pulmonary disease (COPD), interstitial pneumonia, pulmonary interstitial fibrosis, Parkinson's disease, active bleeding, or systemic active infection.
•Any unstable systemic disease, e.g. severe metabolic disease: liver cirrhosis, renal failure, or uremia.

Arms & Interventions

Phase Ib: HSK42360 as monotherapy

Phase 1b: dose expansion for HSK40118 as monotherapy at a dose determined during Phase 1a (Part B) in patients with BRAF V600 mutation locally advanced or metastatic solid tumors

Intervention: HSK42360

Phase Ia (Part A): HSK42360 as monotherapy

Phase 1a (Part A): dose escalation of HSK42360 as monotherapy at various dose levels

Intervention: HSK42360

Phase Ia (Part B): HSK42360 as monotherapy

Phase 1a (Part B): dose extention of HSK42360 as monotherapy at certain dose levels

Intervention: HSK42360