Phase 1/2 Study of HS-10370 in Patients With Advanced Solid Tumors

June 7, 2023 updated by: Jiangsu Hansoh Pharmaceutical Co., Ltd.

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10370 Monotherapy in Patients With Advanced Solid Tumors

HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.

Study Type

Interventional

Enrollment (Estimated)

176

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xiaorong Dong, PhD
  • Phone Number: 13986252286
  • Email: xhzzdxr@126.com

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

  1. Men or women greater than or equal to 18 years
  2. Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable
  3. Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b subjects.
  4. At least one measurable lesion in accordance with RECIST 1.1
  5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1
  6. Estimated life expectancy >12 weeks
  7. Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
  8. Females must have the evidence of non-childbearing potential
  9. Signed and dated Informed Consent Form

Exclusion Criteria:

  1. Treatment with any of the following:

    1. Previous or current treatment with KRAS G12C inhibitors
    2. Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370
    3. Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370
    4. Local radiotherapy for palliation within 2 weeks of the first dose of HS-10370, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10370
    5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370
  2. Inadequate bone marrow reserve or serious organ dysfunction
  3. Uncontrolled pleural, ascites or pericardial effusion
  4. Known and untreated, or active central nervous system metastases
  5. Active autoimmune diseases or active infectious disease
  6. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
  7. History of hypersensitivity to any active or inactive ingredient of HS-10370 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10370
  8. The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator
  9. The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator
  10. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study
  11. History of neuropathy or mental disorders, including epilepsy and dementia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HS-10370（Phase 1a：Dose Escalation）
Subjects with advanced solid tumors will be enrolled in dose escalation cohorts. Dose escalation of HS-10370 will be done to determine maximum tolerated dose.
Drug: HS-10370
HS-10370 will be administered orally once daily in a continuous regimen
Experimental: HS-10370（Phase 1b：Dose Expansion ）
Depending on data obtained from the dose escalation part, dose expansion may proceed with multiple cohorts in subjects with advanced solid tumors having a KRAS G12C mutation.
Drug: HS-10370
HS-10370 will be administered orally once daily in a continuous regimen
Experimental: HS-10370（Phase 2 ）
Subjects with locally advanced or metastatic KRAS G12C mutant NSCLC will be enrolled in phase 2 part to evaluate the efficacy and sufficient safety of HS-10370 as monotherapy.
Drug: HS-10370
HS-10370 will be administered orally once daily in a continuous regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ia：To determine the maximum tolerated dose (MTD)
Time Frame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).
Number of participants with dose limiting toxicity
From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).
2. Phase Ib/II: To evaluate clinical activity/efficacy of HS-10370 by assessment of objective response rate
Time Frame: up to 24 months
Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (DOR)
Time Frame: 24 months
DOR assessed by RECIST 1.1 criteria
24 months
Disease Control Rate (DCR)
Time Frame: 24 months
DCR assessed by RECIST 1.1 criteria
24 months
Progression-free survival (PFS)
Time Frame: 24 months
PFS assessed by RECIST 1.1 criteria
24 months
Overall survival (OS)
Time Frame: 24 months
24 months
Incidence and severity of treatment-emergent adverse events
Time Frame: From baseline until 28 days after the last dose
Number of participants with treatment related adverse events.
From baseline until 28 days after the last dose
Observed maximum plasma concentration (Cmax) after single dose of HS-10370
Time Frame: From pre-dose to 120 hours after single dose on Day 1
In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6
From pre-dose to 120 hours after single dose on Day 1
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10370
Time Frame: From pre-dose to 120 hours after single dose on Day 1
In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6.
From pre-dose to 120 hours after single dose on Day 1
Apparent terminal half-life (T1/2) after single dose of HS-10370
Time Frame: From pre-dose to 120 hours after single dose on Day 1
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.
From pre-dose to 120 hours after single dose on Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jiangsu Hansoh Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Xiaorong Dong, PhD, Union Hospital,Tong Ji Medical College,Huazhong University of Science and Technology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 3, 2022

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

May 5, 2022

First Submitted That Met QC Criteria

May 5, 2022

First Posted (Actual)

May 10, 2022

Study Record Updates

Last Update Posted (Actual)

June 9, 2023

Last Update Submitted That Met QC Criteria

June 7, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-10370-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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