Clinical trial NCT05367778: Phase 1/2 Study of HS-10370 in Patients with Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: Advanced Solid Tumor
KRAS G12C mutation
HS-10370
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-10
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase Ia：To determine the maximum tolerated dose (MTD)
timeFrame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).
measure: 2. Phase Ib/II: To evaluate clinical activity/efficacy of HS-10370 by assessment of objective response rate
timeFrame: up to 24 months
Secondary outcomes:
measure: Incidence and severity of treatment-emergent adverse events
timeFrame: From baseline until 28 days after the last dose
measure: Observed maximum plasma concentration (Cmax) after single dose of HS-10370
timeFrame: From pre-dose to 120 hours after single dose on Day 1
measure: Time to reach maximum plasma concentration (Tmax) after single dose of HS-10370
timeFrame: From pre-dose to 120 hours after single dose on Day 1
measure: Apparent terminal half-life (T1/2) after single dose of HS-10370
timeFrame: From pre-dose to 120 hours after single dose on Day 1
measure: Duration of response (DOR)
timeFrame: 24 months
measure: Disease Control Rate (DCR)
timeFrame: 24 months
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Xiaorong Dong, PhD
role: PRINCIPAL_INVESTIGATOR
References: