Phase I Study of HSK42360 in Solid Tumors With BRAF V600 Mutation

NCT06536400 | Recruiting Phase 1

• 1 other identifier: HSK42360-101
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 13

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (6)

• MTD

  MTD determination: dose limiting toxicity (DLT) rate

  Up to approximately 52 months

• DLTs

  Incidence of dose-limiting toxicities (DLTs) at Cycle 0 and Cycle1

  Up to approximately 52 months

• AEs

  Rate and severity of adverse events of HSK42360 as monotherapy

  Up to approximately 52 months

• RP2D

  RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data

  Up to approximately 52 months

• ECOG Performance Status Scale

  Change of the grade as a part of HSK43260 safety data

  Up to approximately 52 months

• Karnofsky Performance Scale, KPS

  Change of the grade as a part of HSK43260 safety data

  Up to approximately 52 months

Secondary Outcomes (9)

• Overall response rate (ORR)

  Up to approximately 52 months

• Disease control rate (DCR)

  Up to approximately 52 months

• Duration of response (DOR)

  Up to approximately 52 months

• Progression free survival (PFS)

  Up to approximately 52 months

• Overall survival (OS)

  Up to approximately 52 months

Other Outcomes (2)

• circulating tumor DNA (ctDNA)

  Up to approximately 52 months

• phosphorylate ERK (pERK)

  Up to approximately 52 months

Study Arms (3)

Phase Ia (Part A): HSK42360 as monotherapy

EXPERIMENTAL

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

Drug: HSK42360

Phase Ia (Part B): HSK42360 as monotherapy

EXPERIMENTAL

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

Drug: HSK42360

Phase Ib: HSK42360 as monotherapy

EXPERIMENTAL

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

Drug: HSK42360

Interventions

HSK42360 DRUG

Oral administration, QD

Phase Ia (Part A): HSK42360 as monotherapy; Phase Ia (Part B): HSK42360 as monotherapy; Phase Ib: HSK42360 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，Male and female patients, at time of signing informed consent form (ICF).
• ECOG performance status 0-1, or KPS (Karnofsky Performance Status) Score\>60.
• 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 HSK42360.
• 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.

You may not qualify if:

• 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 HSK42360.
• 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 HSK42360.
• 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.
• Treatment with inhibitors/inducers for CYP3A4, or substrates of CYP3A4, CYP2C9, CYP2C8, OATP1B1, OATP1B3, OAT1, OAT3, P-gp or BCRP within 14 days or approximately 5 × t1/2 prior to the first dose of HSK42360, whichever is shorter.
• Patient with cognitive dysfunction, or history of mental illness, other uncontrolled comorbidities, alcohol dependence, hormone dependence or drug abuse.
• Autologous transplantation surgery within 3 months prior to the first dose of HSK42360; Allogeneic transplantation, or stem-cell Transplant surgery within 6 months prior to the first dose of HSK42360; Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of HSK42360.
• Patient with a history of immunodeficiency, including HIV positive, or other acquired/congenital immunodeficiency diseases.
• Any disease of the eyes \> CTCAE v5.0 Grade 1.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (13)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Beijing TianTan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350005, China

RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510145, China

RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530012, China

RECRUITING

The Third People's Hospital of Zhengzhou

Zhengzhou, Henan, 450099, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University

Hangzhou, Zhejiang, 310006, China

RECRUITING

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: July 24, 2024
• First Posted: August 5, 2024
• Study Start: June 25, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): July 7, 2027
• Last Updated: August 5, 2024

Record last verified: 2024-08

Locations

CN (13)