A Phase I Study of HS-10386 in Participants With Advanced Solid Tumors

Official title

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10386 in Participants With Advanced Solid Tumors

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Maximum Tolerated Dose (MTD) or Maximum Applicable Dose (MAD) (Dose Escalation Phase) [Time frame: Up to 21 days from the first dose]
• Objective Response Rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Dose Expansion Phase) [Time frame: Every 6 weeks for the duration of study participation; estimated to be 12 months.]

Secondary outcome measures (12)

• Incidence and Severity of Adverse Events (AEs) [Time frame: From Informed consent until the end of the follow-up period which is defined as 28 days (+7 days) after study treatment is discontinued.]
• Cmax of HS-10386 [Time frame: Approximately 1 month.]
• Tmax of HS-10386 [Time frame: Approximately 1 month.]
• λz of HS-10386 [Time frame: Approximately 1 month.]
• t1/2 of HS-10386 [Time frame: Approximately 1 month.]
• AUC0-t of HS-10386 [Time frame: Approximately 1 month]
• CL/F of HS-10386 [Time frame: Approximately 1 month.]
• ORR defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Dose Escalation Phase) [Time frame: Every 6 weeks for the duration of study participation; estimated to be 12 months.]
• Disease Control Rate (DCR) [Time frame: Every 6 weeks for the duration of study participation; estimated to be 12 months.]
• Duration of Response (DoR) [Time frame: Every 6 weeks for the duration of study participation; estimated to be 12 months.]
• Progression-Free Survival (PFS) [Time frame: Every 6 weeks for the duration of study participation; estimated to be 12 months.]
• Overall Survival (OS) (Dose Expansion Phase) [Time frame: From the time of randomization to death due to any cause, approximately 3 years.]

Eligibility criteria

Inclusion criteria

• Male or female, 18-75 years old.
• 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.
• At least one measurable lesion per RECIST v1.1.
• Willingness to provide fresh or archival tumor biopsy sample.
• 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.
• Willingness to use adequate contraceptive measures throughout the study.
• Ability to comprehend and willingness to sign a written ICF for the study.

Exclusion criteria

• Treatment with any of the following:

• Previous or current treatment with systemic immunotherapy.
• Treatment with anticancer medications or investigational drugs within protocol-defined intervals prior to the first scheduled dose of HS-10386.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 except for alopecia.
• Known additional malignancy.
• History or risk of autoimmune disease.
• Known primary CNS malignancy or symptomatic CNS metastases. Patients with asymptomatic CNS metastases may be enrolled after consultation.
• Inadequate bone marrow reserve or organ function.
• Clinically significant cardiac disease.
• Any evidence of severe or uncontrolled systemic diseases
• 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.
• History of organ transplantation or any medical condition requiring the use of systemic immunosuppressive medications.
• Active HBV or HCV infection that requires treatment.
• Known history of HIV.
• Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.
• 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.
• History of severe anaphylaxis or allergic to any of the components of HS-10386.
• Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Chest Hospital — Shanghai

Identifiers

NCT: NCT05911464 · HS-10386-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗