Testing HS-10376 for advanced non-small cell lung cancer

A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10376 Monotherapy in Patients With Advanced Non-small-Cell Lung Cancer

This study is testing a new oral medication called HS-10376 to see if it can help people with advanced non-small cell lung cancer that has specific genetic mutations.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 380 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Tianjin, Tianjin)
• Trial ID: NCT05435274 on ClinicalTrials.gov

What this trial studies

This phase 1/2 study evaluates HS-10376, an oral small molecular inhibitor targeting EGFR/HER2 Exon 20 insertion mutations in patients with advanced non-small cell lung cancer (NSCLC). The study is divided into two parts: the first part focuses on dose escalation and safety assessment, while the second part aims to evaluate the efficacy of HS-10376 in patients with locally advanced or metastatic NSCLC. Participants will be monitored for safety, tolerability, pharmacokinetics, and clinical activity of the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with locally advanced or metastatic NSCLC who have an EGFR/HER2 Exon 20 insertion mutation and for whom standard treatments are not suitable.

Not a fit: Patients who have previously received treatment with EGFR inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new targeted therapy option for patients with advanced NSCLC harboring specific mutations.

How similar studies have performed: While this approach is novel in targeting the specific mutation with HS-10376, similar studies targeting other mutations in NSCLC have shown promising results.

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, tumor tissue samples can be used to test EGFR/HER2 Exon 20 insertion mutation by central laboratory for 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 Exon 20 insertion inhibitors, HER2 Exon 20 insertion inhibitors or EGFR/HER2 Exon 20 insertion inhibitors
   * Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10376
   * Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10376
   * Local radiotherapy for palliation within 2 weeks of the first dose of HS-10376, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10376
   * Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10376
2. Inadequate bone marrow reserve or serious organ dysfunction
3. Uncontrolled pleural, ascites or pericardial effusion
4. Untreated, symptomatic or active central nervous system metastases
5. Severe or poorly controlled hypertension
6. Immunodeficiency disease and active infectious disease
7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
8. History of hypersensitivity to any active or inactive ingredient of HS-10376 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10376
9. The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator
10. The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator
11. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study
12. History of neuropathy or mental disorders, including epilepsy and dementia

Where this trial is running

Tianjin, Tianjin

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin, China (RECRUITING)

Study contacts

• Study coordinator: Dingzhi Huang

Conditions: Advanced Non-Small-Cell Lung Cancer, NSCLC, Non-Small Cell Lung Cancer, HS-10376, EGFR/HER2 Exon 20 insertion mutation