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
Overview
- Phase
- Phase 1
- Intervention
- GH21
- Conditions
- Non-Small Cell Lung Cancer With EGFR Mutation
- Sponsor
- Suzhou Genhouse Bio Co., Ltd.
- Enrollment
- 94
- Locations
- 6
- Primary Endpoint
- Number of Participants with Dose Limiting Toxicities
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects or their legal representatives can understand and voluntarily sign the written ICF (before the start of screening and any study procedures);
- •Male or female subjects aged ≥18 years;
- •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.).
- •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);
- •Consent to provide samples for genetic testing;
- •Life expectancy of ≥ 3 months;
- •ECOG PS score of 0-1;
- •The subjects must have adequate organ functions;
Exclusion Criteria
- •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;
- •Subjects who have had another investigational new drug or therapy within 4 weeks prior to the first dose of the investigational product;
- •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;
- •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;
- •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;
Arms & Interventions
'GH21+Osimertinib'Group
GH21 Capsules Combined with Osimertinib Mesylate Tablets
Intervention: GH21
'GH21+Osimertinib'Group
GH21 Capsules Combined with Osimertinib Mesylate Tablets
Intervention: Tagrisso
Outcomes
Primary Outcomes
Number of Participants with Dose Limiting Toxicities
Time Frame: 2 years
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle. (phase Ib)
Progression-Free Survival (PFS) Based on RECIST 1.1 Criteria
Time Frame: 2 years
PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first. (phase IIb)
Number of Participants with Adverse Events
Time Frame: 2 years
All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments (phase Ib/ IIa)
Secondary Outcomes
- Objective Response Rate (ORR) Based on RECIST 1.1 Criteria(2 years)
- Overall Survival (OS)(2 years)
- Plasma Peak Concentration (Cmax)(2 years)
- Duration of Response (DOR) Based on RECIST 1.1 Criteria(2 years)
- Disease Control Rate (DCR) Based on RECIST 1.1 Criteria(2 years)
- Time to Cmax (Tmax)(2 years)
- Area under the Plasma Concentration-Time Curve (AUC)(2 years)