Clinical trial NCT05435248: Phase 1/2 Study of HS-10375 in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)
Official title: A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10375 Monotherapy in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic NSCLC
Keywords: Advanced or metastatic NSCLC
EGFR C797S mutation
HS-10375
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-06-28
Enrollment: 354
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: HS-10375 is an oral, highly selective, small molecular inhibitor of EGFR C797S. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10375 in Chinese advanced or metastatic NSCLC.


Eligibility criteria: Inclusion Criteria:

1. Men or women greater than or equal to 18 years.
2. Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .
3. Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II 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:

   * Previous or current treatment with EGFR C797S inhibitors.
   * Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10375.
   * Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10375.
   * Local radiotherapy for palliation within 2 weeks of the first dose of HS-10375, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10375.
   * Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10375.
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-10375 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10375.
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: To determine the maximum tolerated dose (MTD)-Part Ia
timeFrame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days)
measure: To evaluate clinical activity/efficacy of HS-10375 by assessment of objective response rate-Part Ib/II
timeFrame: Time Frame: up to 24 months
Secondary outcomes:
measure: Number of participants with treatment related adverse events
timeFrame: From baseline until 28 days after the last dose
measure: Observed maximum plasma concentration (Cmax) after single dose of HS-10375
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-10375
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-10375
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: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: