A Study to Evaluate Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 Combined With Anti-PD-1 Antibody
- Registration Number
- NCT04866485
- Lead Sponsor
- Harbour BioMed (Guangzhou) Co. Ltd.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 66
- 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 ≤ 1.
- Patients whose organ function must meet the study requirements.
- Males or females with childbearing potential need to use an effective contraceptive method.
- Willing and able to comply with study-specified visits schedule, treatment plan, laboratory examination and other study procedures.
- 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-L1.
- 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.
- A history of interstitial lung disease or non-infectious pneumonia.
- Patients with pleural effusion, pericardial effusion, or ascites.
- Patients that may have other conditions that affect the efficacy or safety evaluation of this study (such as mental disorder, alcoholism, drug abuse, etc.) .
- Women who are pregnant or breastfeeding, or who plan to become pregnant during the study period and within 3 months after the last dose of study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HBM4003+pembrolizumab HBM4003 and pembrolizumab HBM4003 combined with pembrolizumab in subjects with advanced NSCLC and other solid tumors
- Primary Outcome Measures
Name Time Method Part 1a: Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration approximate 21 days DLT observation period was defined as one treatment cycles with a total of 21 days
Part 1b: ORR maximum 2 years Proportion of subjects with complete response (CR) and partial response (PR)
- Secondary Outcome Measures
Name Time Method Cmax maximum 2 years Peak Plasma Concentration
Part 1a: Disease Control Rate, DCR maximum 2 years including proportion of subjects with complete response (CR) and partial response (PR) and stable disease (SD)
Part 1a: ORR maximum 2 years including proportions of subjects with complete response (CR) and partial response (PR)
t1/2 maximum 2 years Terminal half-life
Part 1a: Duration of Response, DOR maximum 2 years Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason)
Part 1a: Duration of Disease Control, DDC maximum 2 years For subjects with Cr, PR or SD, the duration from the time of initial administration to the date of disease progression or death (for any reason) was calculated
Tmax maximum 2 years Time to reach maximum serum concentration
AUC0-last maximum 2 years Area under the plasma concentration versus time curve from time zero to last
AUC0-tau maximum 2 years Area under the serum concentration versus time curve from time zero to the dosing interval tau
UC0-inf maximum 2 years Area under the serum concentration versus time curve from time zero to infinity
Vss maximum 2 years Volume of distribution at steady state
CL maximum 2 years Clearance
Part 1a: Immunogenicity of HBM4003 and pembrolizumab maximum 2 years including the occurrence of positive anti-drug antibodies (ADA). The occurrence of neutralizing antibodies for subjects with positive ADA
Part 1b: Number of subjects experiencing at least one treatment-related AE maximum 2 years Evaluate safety
Part 1b: DCR maximum 2 years including proportion of subjects with CR, PR and SD
Part 1b: DOR maximum 2 years calculate the duration from the first confirmed CR or PR to the date of disease progression or (for any reason) death.
Part 1b: DDC maximum 2 years for subjects with CR, PR or SD, calculate the duration from the time of initial medication to the day of disease progression or (for any reason) death
Part 1b: Overall survival (OS) maximum 2 years the length of time from the start of treatment to the death of the subject (for any reason)
Part 1b: Progression-free survival (PFS) maximum 2 years the length of time from the beginning of treatment to the beginning of disease progression or death (for any reason)
Part 1b: Immunogenicity of HBM4003 and pembrolizumab maximum 2 years including the occurrence of positive anti-drug antibodies (ADA). The occurrence of neutralizing antibodies for subjects with positive ADA.