Phase Ⅰ/Ⅱ Study of the HS-10365 in Patients With Advanced Solid Tumors

NCT ID: NCT05207787

Last Updated: 2023-06-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-09
• Study Completion Date: 2025-12-31

Brief Summary

HS-10365 is a small molecular, oral potent, selective RET inhibitor. The purpose of this study is to investigate the safety/tolerability、the pharmacokinetic profile and efficacy of HS-10365 in Chinese advanced solid tumor patients.

Detailed Description

This is a multicenter, open-label phase 1/2 study in participants with advanced solid tumors, including RET fusion-positive non-small cell lung cancer and other tumors with RET activation. The trial will be conducted in 2 parts: Phase 1 and phase 2. Participants with advanced cancer are eligible if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. The phase 1 study is a dose-escalation study, which is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of single dose and multiple doses of HS-10365 given once every day (QD) or twice every day (BID). A dose of 160 milligrams (mg) twice a day (BID) has been selected as the recommended phase 2 dose (RP2D). Approximately 273 participants with advanced solid tumors harboring a RET gene alteration will be enrolled to one of nine phase 2 cohorts:

Cohort 1: RET fusion non-small cell lung cancer (NSCLC) that has progressed after at least first-line therapy Cohort 2: RET fusion NSCLC not previously treated for metastatic disease Cohort 3: Medullary thyroid carcinoma that has progressed after at least first-line therapy Cohort 4: RET mutation-positive MTC not previously treated for metastatic disease Cohort 5: RET fusion Radioiodine-refractory thyroid cancer Cohort 6: Advanced solid tumors with RET gene fusion except for cohort 1 to 5 Cohort 7: Advanced solid tumors with RET gene abnormalities and drug resistance or intolerance previously treated with RET inhibitors except for cohort 1 to 6 Cohort 8: Advanced solid tumors with RET gene abnormality except for cohort 1 to 7 Cohort 9: NSCLC with RET gene abnormality except for cohort 1 to 2

Conditions

Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Multiple doses of HS-10365 and 160mg BID (recommended Phase 2 dose)

Phase 1 : Multiple doses of HS-10365 for oral administration. Phase 2 : 160 mg BID of HS-10365

Group Type: EXPERIMENTAL

HS-10365

Intervention Type: DRUG

Single or multiple dose(s) of HS-10365 daily or twice every day. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and/or unequivocal disease progression.

Interventions

HS-10365

Single or multiple dose(s) of HS-10365 daily or twice every day. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and/or unequivocal disease progression.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. For Cohort 1 and Cohort 2，patient's cancer has a known primary driver alteration other than RET.

2. For Cohort 1~6 and Cohort 8~9，patients previously treated with a selective RET inhibitor.

3. Treatment with any of the following:

Previous or current treatment with selective RET inhibitors(except for cohort 7). Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days of the first dose of study drug (except for cohort 3 and 7).

Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.

Major surgery within 4 weeks of the first dose of study drug.

4. Inadequate bone marrow reserve or organ function.

5. Uncontrolled pleural effusion or ascites or pericardial effusion.

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

7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10365.

8. History of hypersensitivity to any active or inactive ingredient of HS-10365 or to drugs with a similar chemical structure or class to HS-10365.

9. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

10. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.

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

12. Determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shun Lu, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital, Shanghai JiaoTong University

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shun Lu, MD

Role: CONTACT

shun_lu@hotmail.com

13601813062

Facility Contacts

Shun Lu, MD

Role: primary

Other Identifiers

HS-10365-101

Identifier Type: -

Identifier Source: org_study_id