Phase 1/2 Study of HS-10370 in Patients With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10370 Monotherapy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05367778
• Other study ID #: HS-10370-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 3, 2022
• Est. completion date: April 30, 2026

Study information

• Verified date: April 2023
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Xiaorong Dong, PhD
• Phone: 13986252286
• Email: xhzzdxr[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.

Description:

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 176
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation

in this study:

1. Men or women greater than or equal to 18 years

2. Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable

3. Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b subjects.

4. At least one measurable lesion in accordance with RECIST 1.1

5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1

6. Estimated life expectancy >12 weeks

7. Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.

8. Females must have the evidence of non-childbearing potential

9. Signed and dated Informed Consent Form

Exclusion Criteria:

1. Treatment with any of the following:

1. Previous or current treatment with KRAS G12C inhibitors

2. Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370

3. Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370

4. Local radiotherapy for palliation within 2 weeks of the first dose of HS-10370, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10370

5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370

2. Inadequate bone marrow reserve or serious organ dysfunction

3. Uncontrolled pleural, ascites or pericardial effusion

4. Known and untreated, or active central nervous system metastases

5. Active autoimmune diseases or active infectious disease

6. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications

7. History of hypersensitivity to any active or inactive ingredient of HS-10370 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10370

8. The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator

9. The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator

10. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study

11. History of neuropathy or mental disorders, including epilepsy and dementia

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• HS-10370
HS-10370 will be administered orally once daily in a continuous regimen

Locations

Country	Name	City	State
China	Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ia:To determine the maximum tolerated dose (MTD)	Number of participants with dose limiting toxicity	From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).
Primary	2. Phase Ib/II: To evaluate clinical activity/efficacy of HS-10370 by assessment of objective response rate	Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	up to 24 months
Secondary	Incidence and severity of treatment-emergent adverse events	Number of participants with treatment related adverse events.	From baseline until 28 days after the last dose
Secondary	Observed maximum plasma concentration (Cmax) after single dose of HS-10370	In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6	From pre-dose to 120 hours after single dose on Day 1
Secondary	Time to reach maximum plasma concentration (Tmax) after single dose of HS-10370	In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6.	From pre-dose to 120 hours after single dose on Day 1
Secondary	Apparent terminal half-life (T1/2) after single dose of HS-10370	Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by ?z.	From pre-dose to 120 hours after single dose on Day 1
Secondary	Duration of response (DOR)	DOR assessed by RECIST 1.1 criteria	24 months
Secondary	Disease Control Rate (DCR)	DCR assessed by RECIST 1.1 criteria	24 months
Secondary	Progression-free survival (PFS)	PFS assessed by RECIST 1.1 criteria	24 months
Secondary	Overall survival (OS)		24 months