Combining GH21 Capsules with Osimertinib for Non-Small Cell Lung Cancer

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Oral Administration of GH21 Capsules Combined With Osimertinib Mesylate Tablets in Patients With Advanced NSCLC With EGFR Mutations

This study is testing if combining GH21 capsules with Osimertinib can help people with advanced Non-Small Cell Lung Cancer that has specific genetic changes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 94 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Suzhou Genhouse Bio Co., Ltd. (Academic / other)
• Drugs / interventions: Osimertinib, Furmonertinib, Almonertinib, chemotherapy
• Locations: 6 sites (Hefei, Anhui and 5 other locations)
• Trial ID: NCT06306456 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of GH21 capsules in combination with Osimertinib mesylate tablets for patients with advanced Non-Small Cell Lung Cancer (NSCLC) harboring EGFR mutations. The study is structured in three phases: Phase Ib focuses on determining the recommended dose escalation using a classic '3+3' design, while Phase IIa assesses two different dosing cohorts. Phase IIb will further evaluate the safety and efficacy based on data collected from the earlier phases to finalize the dosing strategy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced NSCLC and confirmed EGFR mutations who have previously progressed on third-generation EGFR-TKIs.

Not a fit: Patients who have not been previously treated with third-generation EGFR-TKIs or those with non-EGFR mutated NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced NSCLC who have limited treatment alternatives.

How similar studies have performed: Other studies combining targeted therapies for NSCLC have shown promising results, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Subjects or their legal representatives can understand and voluntarily sign the written ICF (before the start of screening and any study procedures);
2. Male or female subjects aged ≥18 years;
3. Advanced NSCLC patients with EGFR mutations confirmed by cytological or histological assessments, and meet the following requirement:

   * Phase Ib： patients with disease progression previously at least treated with third-generation EGFR-TKIs and platinum-containing chemotherapy;
   * Phase IIa and IIb：patients with disease progression previously at least treated with a third-generation EGFR-TKIs (Osimertinib, Furmonertinib Almonertinib etc.).
4. Patients have at least one measurable lesion as defined by RECIST v1.1 (a tumor lesion in the area that has undergone radiotherapy or other loco-regional therapies, is generally not considered as measurable unless there is a disease progression in the lesion);
5. Consent to provide samples for genetic testing;
6. Life expectancy of ≥ 3 months;
7. ECOG PS score of 0-1;
8. The subjects must have adequate organ functions;
9. Male and female of reproductive potential must agree to take reliable contraceptive measures (hormone or barrier methods or abstinence) from signing the ICF until 30 days after the last dose. Pregnancy test results must be negative for female of reproductive potential within 7 days prior to the first dose of the investigational product.

Exclusion Criteria:

1. Subjects who receive any chemotherapy or antitumor biologics within 3 weeks, or antitumor therapies such as radiotherapy and endocrine therapy within 4 weeks prior to the first dose of the investigational product, except for the following:

   * Use of nitrosoureas or mitomycin C within 6 weeks prior to the first dose of the investigational product;
   * Oral administration of fluorouracils, small molecule targeted drugs, and Chinese herbal medicines or Chinese patent medicines with antitumor indications within 5 half-lives or 2 weeks before the first dose of the investigational product (whichever is shorter);
   * Small molecule TKI inhibitors within 5 half-lives or 2 weeks prior to the first dose of the investigational product (whichever is shorter);
   * Local palliative radiotherapy within 2 weeks prior to the first dose of the investigational product;
2. Subjects who have had another investigational new drug or therapy within 4 weeks prior to the first dose of the investigational product;
3. Subjects who have had a major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose of the investigational product, or require an elective surgery during the study;
4. Subjects who have received strong CYP3A4 inhibitors or inducers and strong P-gp inhibitors or inducers within 2 weeks or within 5 half-lives (whichever is longer) prior to the first dose of the investigational product;
5. Subjects with evidence of the following heart conditions:

   * Acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, cerebrovascular accident, or transient ischemic attack within 6 months prior to the first dose of the investigational product;
   * Grade III-IV heart failure diagnosed according to the cardiac function classification of the New York Heart Association at screening;
   * Echocardiography (ECHO) shows the left ventricular ejection fraction (LVEF) ≤ 50% at screening;
   * QT interval corrected by Fridericia method (QTcF) is ≥ 450 ms (male) or ≥ 470 ms (female) at screening;
   * Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) despite of medication treatment at screening;
6. Subjects with dysphagia, gastrointestinal disorders that affect drug absorption, or other malabsorption conditions, such as intestinal obstruction, Crohn's disease, ulcerative colitis, short bowel syndrome, delayed gastric emptying, or severe gastrointestinal toxicities that have not resolved to Grade 2 or lower prior to the first dose of the investigational product; or subjects are diagnosed with a clinically significant or acute gastrointestinal disease;
7. Subjects with poorly controlled clinical pleural ascites assessed by the investigator;
8. Subjects with active central nervous system metastasis and/or carcinomatous meningitis (e.g., brain metastases accompanied by central nervous system symptoms, including headache, vomiting and dizziness, etc.);
9. Subjects with interstitial pneumonia, or any evidence of clinically active interstitial lung disease within 6 months before the first dose of the investigational product;
10. Subjects with a history of other malignancies (excluding those deemed eligible by the investigator, such as skin squamous cell carcinoma in situ, basal cell carcinoma, and cervical cancer in situ that have been cured and have not relapsed for 5 years; or subjects deemed eligible by the investigator in Phase Ib);
11. Subjects with a history of severe allergies, a history of allergies to Osimertinib, or to multiple drugs;
12. Subjects with hepatitis B virus infection (HBsAg positivity and DNA copies \< 100 IU/mL); or hepatitis C virus infection (HCV antibody positivity, and HCV RNA \> ULN); or human immunodeficiency virus infection (HIV antibody positivity);
13. Subjects with active infections requiring anti-infective treatment (Grade ≥ 2) or fever \> 38°C of unknown etiology within 28 days prior to the first dose of the investigational product;
14. Subjects with any toxicity caused by a previous antitumor therapy that has not resolved to Grade ≤ 1 according to CTCAE 5.0 (except for alopecia, Grade 2 peripheral neuropathy, and/or other Grade ≤ 2 AEs of insignificant safety risks) before the first dose of the investigational product;
15. Female subjects who are pregnant or breastfeeding;
16. Subjects who are not suitable for this study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator.

Where this trial is running

Hefei, Anhui and 5 other locations

• The Second Hospital of Anhui Medical University — Hefei, Anhui, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (Recruiting)
• Shanghai Pulmonary Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Taizhou Hospital of Zhejiang Province — Linhai, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Caicun Zhou, Doctorate — （86）021-65115006
• Study coordinator: Yiming Zhou, Bachelor

Conditions Non-Small Cell Lung Cancer With EGFR Mutation