A Phase Ib/II Clinical Study of GH21 Capsules Combined With Osimertinib Mesylate Tablets in Patients With NSCLC

NCT ID: NCT06306456

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-05
• Study Completion Date: 2026-12-31

Brief Summary

This study, including phase Ib , phase IIa and phase IIb, aims to evaluate the safety, tolerability, PK profile, efficacy and to determine the RP2D of GH21 capsules combined with Osimertinib mesylate tablets in NSCLC patients with EGFR mutations.

Detailed Description

Phase Ib: Classic "3+3" design used for Phase 1b to select the putative RDEs. Four dose groups are preset in phase Ib of this study, which including QD groups and BIW groups. Subjects will be enrolled in parallel cross into the group.

Phase IIa: Two cohorts are preset in this stage, Cohort 1: GH21 RDE1 QD + Osimertinib 80 mg QD, Cohort 2: GH21 RDE2 D1D2-BIW + Osimertinib 80 mg QD, Cohort 1 and Cohort 2 are enrolled in parallel.

Phase IIb: Phase IIb preset 1 cohort. The investigator and sponsor will comprehensively evaluate safety, efficacy, and PK data from Phases Ib and IIa to determine the dose level for Phase IIb.

Conditions

Non-Small Cell Lung Cancer With EGFR Mutation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

'GH21+Osimertinib'Group

GH21 Capsules Combined with Osimertinib Mesylate Tablets

Group Type: EXPERIMENTAL

GH21

Intervention Type: DRUG

Oral, 15mg BIW/6mg QD

Tagrisso

Intervention Type: DRUG

Oral, 80mg QD

Interventions

GH21

Oral, 15mg BIW/6mg QD

Intervention Type: DRUG

Tagrisso

Oral, 80mg QD

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suzhou Genhouse Bio Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Caicun Zhou, Doctorate

Role: PRINCIPAL_INVESTIGATOR

（86）021-65115006

Haidan Wang, Doctorate

Role: STUDY_DIRECTOR

（86）0512-86861608

Locations

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Site Status: NOT_YET_RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status: NOT_YET_RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status: RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Taizhou Hospital of Zhejiang Province

Linhai, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yiming Zhou, Bachelor

Role: CONTACT

zhouyiming@genhousebio.com

（86）0512-86861608

Facility Contacts

Mingjun Zhang, Doctorate

Role: primary

mjzhang2010@outlook.com

(86)0551-63869420

Sanxing Guo, Doctorate

Role: primary

sanxing134@hotmail.com

(86)0371-67966266

Yongchang Zhang, Doctorate

Role: primary

zhangyongchang@csu.edu.cn

(86)0731-88651900

Yongsheng Wang, Doctorate

Role: primary

dolphin8012@yahoo.com

（86）025-83304616

Caicun Zhou, Doctorate

Role: primary

caicunzhoudr@163.com

（86）021-65115006

Dongqing Lv, Master's degree

Role: primary

lvdq@enzemed.com

（86）0576-85120120

Other Identifiers

GH21C201

Identifier Type: -

Identifier Source: org_study_id