An Open-Label, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 in Combination With Anti-PD-1 Monoclonal Antibody in Patients With Advanced NSCLC and Other Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- HBM4003 and pembrolizumab
- Conditions
- Solid Tumor
- Sponsor
- Harbour BioMed (Guangzhou) Co. Ltd.
- Enrollment
- 66
- Primary Endpoint
- Part 1a: Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration
- Last Updated
- 5 years ago
Overview
Brief Summary
This is an open-label, multi-center phase 1 study. The trial, consisting of Part 1a dose confirmation and Part 1b dose expansion, is designed to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with pembrolizumab in patients with advanced NSCLC and other solid tumors.
Detailed Description
subjects will be treated with HBM4003 in combination with pembrolizumab for up to 2 years or until confirmed disease progression, unacceptable tolerability or treatment discontinuation through withdrawal of consent occurs, whichever happens first. This trial consists of : * A screening period: 28 days * A treatment period: * Part 1a dose confirmation study * Part 1b dose expansion study * A post-treatment follow-up period, including * A safety follow-up period: 28 days after the last dose of study drug; * Post-treatment follow-up visit: day 84 after the last dose of study drug; * Survival follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients ≥18 years old at the time of signing the informed consent and ≤ 75 years old at the time of enrollment.
- •Patients for Part 1a: patients diagnosed with advanced or recurrent solid tumors.
- •Patients for Part 1b: patients diagnosed with metastatic NSCLC and confirmed with negative tumor PD-L1 expression (TPS\<1%).
- •Patients for Part 1b dose expansion study: have never received systemic therapies as primary therapy for advanced or metastatic diseases.
- •Patients must be able to provide fresh tumor tissues or archived tumor tissues.
- •Patients whose estimated survival time is more than 3 months.
- •Patients with at least one measurable lesion at baseline according to RECIST (version 1.1).
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status score ≤
- •Patients whose organ function must meet the study requirements.
- •Males or females with childbearing potential need to use an effective contraceptive method.
Exclusion Criteria
- •NSCLC patients with EGFR-sensitive mutations or an ALK translocation based on diagnosis results.
- •Patients who are simultaneously participating in another clinical study, unless the study is an observational (non-interventional) clinical study or the patient is already in the survival follow-up period of the interventional study.
- •Patients with a medical history of severe allergic diseases, a history of severe drug allergies, and are known or suspected allergy to macromolecular protein preparations or HBM4003 or pembrolizumab excipients.
- •Previous and concomitant drugs or treatments to be excluded like CTLA4, PD-1,PD-L
- •Insufficient completely recovery from previous treatments.
- •Diseases that may affect the efficacy and safety of the investigational product.
- •A history of other malignant diseases within 5 years before the first dose.
- •Active brain metastasis or leptomeningeal metastasis during screening or previous with imaging evidence (based on CT or MRI assessment).
- •Patients who have received palliative radiotherapy for non-central nervous system lesions within 2 weeks before the first dose.
- •Patients who have received more than 30 Gy of lung radiation therapy within 6 months before the first dose.
Arms & Interventions
HBM4003+pembrolizumab
HBM4003 combined with pembrolizumab in subjects with advanced NSCLC and other solid tumors
Intervention: HBM4003 and pembrolizumab
Outcomes
Primary Outcomes
Part 1a: Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration
Time Frame: approximate 21 days
DLT observation period was defined as one treatment cycles with a total of 21 days
Part 1b: ORR
Time Frame: maximum 2 years
Proportion of subjects with complete response (CR) and partial response (PR)
Secondary Outcomes
- Part 1b: DCR(maximum 2 years)
- Part 1a: Disease Control Rate, DCR(maximum 2 years)
- Part 1a: ORR(maximum 2 years)
- t1/2(maximum 2 years)
- Part 1a: Duration of Response, DOR(maximum 2 years)
- Part 1a: Duration of Disease Control, DDC(maximum 2 years)
- Cmax(maximum 2 years)
- Tmax(maximum 2 years)
- AUC0-last(maximum 2 years)
- AUC0-tau(maximum 2 years)
- UC0-inf(maximum 2 years)
- Vss(maximum 2 years)
- CL(maximum 2 years)
- Part 1a: Immunogenicity of HBM4003 and pembrolizumab(maximum 2 years)
- Part 1b: Number of subjects experiencing at least one treatment-related AE(maximum 2 years)
- Part 1b: DOR(maximum 2 years)
- Part 1b: DDC(maximum 2 years)
- Part 1b: Overall survival (OS)(maximum 2 years)
- Part 1b: Progression-free survival (PFS)(maximum 2 years)
- Part 1b: Immunogenicity of HBM4003 and pembrolizumab(maximum 2 years)