A Phase I Study of HS-10386 in Participants With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of HS-10386 in participants with advanced solid tumors who have failed prior treatments.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This is a phase I open label, multicenter clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of HS-10386 in subjects with advanced solid tumors.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: HS-10386 Participants will receive HS-10386 once daily. The duration of each treatment cycle is 21 days. |
Drug: HS-10386
Starting dose 10 mg, administered once daily. If tolerated, subsequent cohorts will test increasing doses of HS-10386, until a maximum tolerated dose (MTD) or maximum applicable dose (MAD) is defined
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Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) or Maximum Applicable Dose (MAD) (Dose Escalation Phase) [Up to 21 days from the first dose]
MTD is defined as the dose level immediately below that at which 2 or more patients exhibit dose limiting toxicity. MAD is defined as the maximum administered dose, when MTD is not reached.
- Objective Response Rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Dose Expansion Phase) [Every 6 weeks for the duration of study participation; estimated to be 12 months.]
ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression.
Secondary Outcome Measures
- Incidence and Severity of Adverse Events (AEs) [From Informed consent until the end of the follow-up period which is defined as 28 days (+7 days) after study treatment is discontinued.]
The number and percentage of patients that experience an AE. The severity of AEs are assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.
- Cmax of HS-10386 [Approximately 1 month.]
Cmax is defined as the maximum observed plasma or serum concentration.
- Tmax of HS-10386 [Approximately 1 month.]
Tmax is defined as the time to maximum concentration.
- λz of HS-10386 [Approximately 1 month.]
λz is defined as the apparent terminal-phase disposition rate constant.
- t1/2 of HS-10386 [Approximately 1 month.]
t1/2 is defined as the apparent terminal-phase disposition half-life.
- AUC0-t of HS-10386 [Approximately 1 month]
AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
- CL/F of HS-10386 [Approximately 1 month.]
CL/F is defined as the apparent oral dose clearance.
- ORR defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Dose Escalation Phase) [Every 6 weeks for the duration of study participation; estimated to be 12 months.]
ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression.
- Disease Control Rate (DCR) [Every 6 weeks for the duration of study participation; estimated to be 12 months.]
The DCR is defined as the percentage of patients with a best overall response of CR, PR, or SD.
- Duration of Response (DoR) [Every 6 weeks for the duration of study participation; estimated to be 12 months.]
DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
- Progression-Free Survival (PFS) [Every 6 weeks for the duration of study participation; estimated to be 12 months.]
PFS was defined as the time from random assignment (dose expansion stage) or first dose (dose escalation stage) to PD or death from any cause.
- Overall Survival (OS) (Dose Expansion Phase) [From the time of randomization to death due to any cause, approximately 3 years.]
OS is defined as the time from randomization to death due to any cause.
- The correlation between PD-L1 expression and efficacy of HS-10386 [Approximately 3 years.]
The study will collect tumor tissue samples during screening period and after the treatment. Stratified analysis of the efficacy endpoint of HS-10386 (such as object response, DoR, PFS, etc.) by PD-L1 expression level will be performed to assess the correlation between PD-L1 expression as biomarker and study dose and effeicacy of HS-10386.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female, 18-75 years old.
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Histologically or cytologically documented, incurable or metastatic solid tumors for which standard treatment either does not exist or has proven ineffective or unavailable or intolerable.
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At least one measurable lesion per RECIST v1.1.
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Willingness to provide fresh or archival tumor biopsy sample.
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An Eastern Cooperative Oncology Group (ECOG) performance status equal to 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
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Willingness to use adequate contraceptive measures throughout the study.
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Ability to comprehend and willingness to sign a written ICF for the study.
Exclusion Criteria:
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Treatment with any of the following:
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Previous or current treatment with systemic immunotherapy.
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Treatment with anticancer medications or investigational drugs within protocol-defined intervals prior to the first scheduled dose of HS-10386.
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Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 except for alopecia.
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Known additional malignancy.
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History or risk of autoimmune disease.
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Known primary CNS malignancy or symptomatic CNS metastases. Patients with asymptomatic CNS metastases may be enrolled after consultation.
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Inadequate bone marrow reserve or organ function.
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Clinically significant cardiac disease.
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Any evidence of severe or uncontrolled systemic diseases
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Severe infections within 4 weeks prior to the first scheduled dose or symptoms of infection within 2 weeks prior to prior to the first scheduled dose.
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History of organ transplantation or any medical condition requiring the use of systemic immunosuppressive medications.
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Active HBV or HCV infection that requires treatment.
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Known history of HIV.
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Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.
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Administration of a live, attenuated vaccine within 4 weeks prior to the first scheduled dose or anticipation that such a live attenuated vaccine will be required during the study.
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History of severe anaphylaxis or allergic to any of the components of HS-10386.
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Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Shanghai Chest Hospital | Shanghai | Shanghai | China | 200030 |
Sponsors and Collaborators
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
Investigators
- Principal Investigator: Shun Lu, Dr., Shanghai Chest Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HS-10386-101