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

NCT05367778 | Recruiting Phase 1

• 1 other identifier: HS-10370-101
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; KRAS G12C mutation; HS-10370

Outcome Measures

Primary Outcomes (2)

• Phase Ia：To determine the maximum tolerated dose (MTD)

  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

  Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

  up to 24 months

Secondary Outcomes (8)

• Incidence and severity of treatment-emergent adverse events

  From baseline until 28 days after the last dose

• Observed maximum plasma concentration (Cmax) after single dose of HS-10370

  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

  From pre-dose to 120 hours after single dose on Day 1

• Apparent terminal half-life (T1/2) after single dose of HS-10370

  From pre-dose to 120 hours after single dose on Day 1

• Duration of response (DOR)

  24 months

Study Arms (3)

HS-10370（Phase 1a：Dose Escalation）

EXPERIMENTAL

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（Phase 1b：Dose Expansion ）

EXPERIMENTAL

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（Phase 2 ）

EXPERIMENTAL

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

Interventions

HS-10370 DRUG

HS-10370 will be administered orally once daily in a continuous regimen

HS-10370（Phase 1a：Dose Escalation）; HS-10370（Phase 1b：Dose Expansion ）; HS-10370（Phase 2 ）

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women greater than or equal to 18 years
• Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable
• Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b subjects.
• At least one measurable lesion in accordance with RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status: 0\~1
• Estimated life expectancy \>12 weeks
• 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.
• Females must have the evidence of non-childbearing potential
• Signed and dated Informed Consent Form

You may not qualify if:

• Treatment with any of the following:
• Previous or current treatment with KRAS G12C inhibitors
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370
• Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370
• 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
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370
• Inadequate bone marrow reserve or serious organ dysfunction
• Uncontrolled pleural, ascites or pericardial effusion
• Known and untreated, or active central nervous system metastases
• Active autoimmune diseases or active infectious disease
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
• 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
• The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator
• The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator
• Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Study Officials

• Xiaorong Dong, PhD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaorong Dong, PhD

CONTACT

13986252286; xhzzdxr@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 10, 2022
• Study Start: June 3, 2022
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)