Trial Title:
A Phase Ib/II Clinical Study of GH21 Capsules Combined With Osimertinib Mesylate Tablets in Patients With NSCLC
NCT ID:
NCT06306456
Condition:
Non-Small Cell Lung Cancer With EGFR Mutation
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Osimertinib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GH21
Description:
Oral, 15mg BIW/6mg QD
Arm group label:
'GH21+Osimertinib'Group
Intervention type:
Drug
Intervention name:
Tagrisso
Description:
Oral, 80mg QD
Arm group label:
'GH21+Osimertinib'Group
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Hospital of Anhui Medical University
Address:
City:
Hefei
Zip:
230601
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Mingjun Zhang, Doctorate
Phone:
(86)0551-63869420
Email:
mjzhang2010@outlook.com
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Zip:
450000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Sanxing Guo, Doctorate
Phone:
(86)0371-67966266
Email:
sanxing134@hotmail.com
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongchang Zhang, Doctorate
Phone:
(86)0731-88651900
Email:
zhangyongchang@csu.edu.cn
Facility:
Name:
Nanjing Drum Tower Hospital
Address:
City:
Nanjing
Zip:
210008
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongsheng Wang, Doctorate
Phone:
(86)025-83304616
Email:
dolphin8012@yahoo.com
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Zip:
200433
Country:
China
Status:
Recruiting
Contact:
Last name:
Caicun Zhou, Doctorate
Phone:
(86)021-65115006
Email:
caicunzhoudr@163.com
Facility:
Name:
Taizhou Hospital of Zhejiang Province
Address:
City:
Linhai
Zip:
317099
Country:
China
Status:
Recruiting
Contact:
Last name:
Dongqing Lv, Master's degree
Phone:
(86)0576-85120120
Email:
lvdq@enzemed.com
Start date:
March 5, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Suzhou Genhouse Bio Co., Ltd.
Agency class:
Other
Source:
Suzhou Genhouse Bio Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06306456