Testing HS-10365 for advanced solid tumors

A Phase 1/2, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Single and Multiple Doses of Oral Administration of HS-10365 in Patients With Locally Advanced or Metastatic Solid Tumors

This study is testing a new drug called HS-10365 to see if it can help people with advanced solid tumors that have specific gene changes, especially if their cancer hasn't responded to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 306 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05207787 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label phase 1/2 study investigates the safety, tolerability, pharmacokinetics, and efficacy of HS-10365, a selective RET inhibitor, in patients with advanced solid tumors, particularly those with RET gene alterations. The trial consists of two phases: a dose-escalation phase to determine the optimal dose and a subsequent phase to evaluate the drug's effectiveness in various cohorts of patients with specific types of RET-positive tumors. Participants must have advanced cancer that has progressed on or is intolerant to standard therapies. The study aims to enroll approximately 273 participants across multiple cohorts.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors that have RET gene alterations and have either progressed on or are intolerant to standard treatments.

Not a fit: Patients without RET gene alterations or those with early-stage tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors harboring RET gene alterations.

How similar studies have performed: While this approach is focused on a specific RET inhibitor, similar studies targeting RET alterations in tumors have shown promise, indicating potential for success.

Eligibility criteria

For phase 1:

1. Men or women aged more than or equal to (≥) 18 years.
2. Locally advanced or metastatic cancer patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
3. Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor as determined by local or central testing. And tumor tissue samples should be provided before the first administration for retrospective detection of RET gene status; blood samples are also allowed.
4. At least one extra-cranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0\~1.
6. Estimated life expectancy greater than (\>) 12 weeks.
7. Men or women should be using adequate contraceptive measures throughout the study; Females should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study
8. Females must have evidence of non-childbearing potential.
9. Signed and dated Informed Consent Form.

For phase 2:

As for phase 1 with the following modifications:

1. For Cohort 1: Participants must have progressed following at least first-line treatment following platinum-based chemotherapy combined with or sequential PD-1/PD-L1 immunotherapy； For Cohort 2: Recurrence after previous surgical treatment must meet the conditions of having completed radical surgery for at least 6 month； For Cohort 4: Stage III patients with MTC who are unfit/intolerant or refuse radical surgical treatment and have symptoms or rapid disease progression； For Cohort 5: Recurrence after previous surgical treatment must meet the requirements of 12 months or more after the completion of radical surgery;
2. For Cohort 1 and Cohort 2: Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor as determined by central testing.

   For Cohort 3\~9: Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor as determined by local or central testing.
3. For Cohort 1 \~7: At least one measurable lesion as defined by RECIST 1.1.

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.

Where this trial is running

Shanghai, Shanghai

• Shanghai Chest Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Shun Lu, MD — Shanghai Chest Hospital, Shanghai JiaoTong University
• Study coordinator: Shun Lu, MD

Conditions Solid Tumor; Advanced solid tumor; RET gene activation