Solid TumorPhase 1/2NCT05207787
Phase Ⅰ/Ⅱ Study of the HS-10365 in Patients With Advanced Solid Tumors
A Phase 1/2 study testing HS-10365 in people with Solid Tumor, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- HS-10365
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 306 participants
- Where
- 1 siteChina
- Study dates
- 9 Nov 2021to 31 Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- For Cohort 1 and Cohort 2，patient's cancer has a known primary driver alteration other than RET.
- For Cohort 1~6 and Cohort 8~9，patients previously treated with a selective RET inhibitor.
- 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.
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- Inadequate bone marrow reserve or organ function.
- Uncontrolled pleural effusion or ascites or pericardial effusion.
- Known and untreated, or active central nervous system metastases.
- Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10365.
- 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.
- 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.
- 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.
- History of neuropathy or mental disorders, including epilepsy and dementia
- Determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Chest Hospital
Shanghai, Shanghai Municipality
Shun Lu, MD
About this study
Official title: 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
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.
Read the 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
- Being tested
- HS-10365
- Keywords
- Advanced solid tumor, RET gene activation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HS-10365Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Multiple doses of HS-10365 and 160mg BID (recommended Phase 2 dose) | Experimental | Phase 1 : Multiple doses of HS-10365 for oral administration. Phase 2 : 160 mg BID of HS-10365 Receives: Drug: HS-10365 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: To determine the maximum tolerated dose (MTD) or maximum administrated dose(MAD)
MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a dose limiting toxicity (DLT).
Measured: Up to 28 days.
Phase 2: Response Rate (ORR) assessed by independent review committee (IRC)
anti-tumor efficacy will be assessed by best radiographic response based on response evaluation criteria in solid tumors at baseline (Day -28 to -1). For patients that continue on repeating 28-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks before 18 weeks of therapy and then each 12 weeks. ORR is defined as the percentage of patients with a CR or PR that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.
Measured: From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study, whichever came first, up to 24 months.
Secondary outcomes (11)
Incidence and severity of treatment-emergent adverse events
Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, and NCI CTCAE v5.0.
Measured: From baseline until 28 days after the last dose
Observed maximum plasma concentration (Cmax) after single dose of HS-10365
n the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10365 on Day 1 to Day 6.
Measured: From pre-dose to 120 hours after single dose on Day 1
Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10365
At multiple-dose, Cmax ss will be obtained on Day 1 of dosing in the following 21-Day cycles of therapy.
Measured: From pre-dose to 24 hours after the first dose of multiple dosing on Day 1 of the following 21-Day cycles of therapy
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10365
In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10365 on Day 1 to Day 6.
Measured: From pre-dose to 120 hours after single dose on Day 1
Apparent terminal half-life (T1/2) after single dose of HS-10365
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 λz.
Measured: From pre-dose to 120 hours after single dose on Day 1
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10365
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: From pre-dose to 120 hours after single dose on Day 1
ORR of HS-10365
Anti-tumor efficacy will be assessed by best radiographic response based on response evaluation criteria in solid tumors at baseline (Day -28 to -1). For patients that continue on repeating 28-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks before 18 weeks of therapy and then each 12 weeks. ORR is defined as the percentage of patients with a CR or PR that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.
Measured: From the date of first occurrence of CR or PR on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study, whichever came first, up to 24 months]（Only phase 1）
Disease control rate of HS-10365 (DCR)
Objective response was assessed by RECIST 1.1 thereby to evaluate disease control rate. Disease control was defined as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 5 weeks).
Measured: From the first occurrence of confirmed CR or PR or SD until the date of disease progression or withdrawal from study, whichever came first, up to 24 months.
Duration of response of HS-10365 (DoR)
Duration of response assessed by RECIST 1.1. Duration of response was defined as the time from when the criteria for CR or PR were first met to the occurrence of a objective disease progression (PD) or death.
Measured: From the date of the first dose to disease progression or death in patients who achieve CR or PR, whichever came first, up to 24 months.
Progression-free survival of HS-10365 (PFS)
Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival. Progression-free survival was defined as the time from date of first dose until the documentation of objective PD or death from any cause in the absence of progression (whichever occurred first), regardless of whether they subsequently received non-study anti-cancer therapy.
Measured: From the date of the first dose until the date of disease progression or death from any cause, whichever came first, up to 24 months.
Overall survival (OS)
Overall survival (OS)
Measured: The time from initial administration to death from any cause, up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start9 Nov 2021
- Primary completion30 Apr 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Jiangsu Hansoh Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 306 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shun Lu, MD, Principal investigator, Shanghai Chest Hospital, Shanghai JiaoTong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05207787
- Sponsor's protocol ID
- HS-10365-101
- Status last verified
- Mar 2023
- First submitted
- 9 Jan 2022
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05207787
- Acronym / sponsor ID
- HS-10365-101
- Conditions
- Solid Tumor
- Keywords
- Advanced solid tumor, RET gene activation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 306 participants (estimated)
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 9 Nov 2021 (actual)
- Primary completion
- 30 Apr 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple doses of HS-10365 and 160mg BID (recommended Phase 2 dose) | Experimental | Drug: HS-10365Phase 1 : Multiple doses of HS-10365 for oral administration. Phase 2 : 160 mg BID of HS-10365 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- For Cohort 1 and Cohort 2，patient's cancer has a known primary driver alteration other than RET.
- For Cohort 1~6 and Cohort 8~9，patients previously treated with a selective RET inhibitor.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HS-10365Single 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. | Drug | Multiple doses of HS-10365 and 160mg BID (recommended Phase 2 dose) |
Primary outcome
Phase 1: To determine the maximum tolerated dose (MTD) or maximum administrated dose(MAD)
Time frame: Up to 28 days.
MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a dose limiting toxicity (DLT).
Phase 2: Response Rate (ORR) assessed by independent review committee (IRC)
Time frame: From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study, whichever came first, up to 24 months.
anti-tumor efficacy will be assessed by best radiographic response based on response evaluation criteria in solid tumors at baseline (Day -28 to -1). For patients that continue on repeating 28-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks before 18 weeks of therapy and then each 12 weeks. ORR is defined as the percentage of patients with a CR or PR that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.
11 secondary outcomes
Incidence and severity of treatment-emergent adverse events
Time frame: From baseline until 28 days after the last dose
Observed maximum plasma concentration (Cmax) after single dose of HS-10365
Time frame: From pre-dose to 120 hours after single dose on Day 1
Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10365
Time frame: From pre-dose to 24 hours after the first dose of multiple dosing on Day 1 of the following 21-Day cycles of therapy
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10365
Time frame: From pre-dose to 120 hours after single dose on Day 1
Apparent terminal half-life (T1/2) after single dose of HS-10365
Time frame: From pre-dose to 120 hours after single dose on Day 1
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10365
Time frame: From pre-dose to 120 hours after single dose on Day 1
ORR of HS-10365
Time frame: From the date of first occurrence of CR or PR on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study, whichever came first, up to 24 months]（Only phase 1）
Disease control rate of HS-10365 (DCR)
Time frame: From the first occurrence of confirmed CR or PR or SD until the date of disease progression or withdrawal from study, whichever came first, up to 24 months.
Duration of response of HS-10365 (DoR)
Time frame: From the date of the first dose to disease progression or death in patients who achieve CR or PR, whichever came first, up to 24 months.
Progression-free survival of HS-10365 (PFS)
Time frame: From the date of the first dose until the date of disease progression or death from any cause, whichever came first, up to 24 months.
Overall survival (OS)
Time frame: The time from initial administration to death from any cause, up to 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shun Lu, MD principal investigator
Shanghai Chest Hospital, Shanghai JiaoTong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HS-10365 in people with Solid Tumor, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shun Lu, MD (13601813062, shun_lu@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: To determine the maximum tolerated dose (MTD) or maximum administrated dose(MAD) (time frame: Up to 28 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2023.