Clinical trial NCT04866485: A Study to Evaluate Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 Combined With Anti-PD-1 Antibody
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 ≤ 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.

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-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.

Primary outcomes:
measure: Part 1a: Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration
timeFrame: approximate 21 days
measure: Part 1b: ORR
timeFrame: maximum 2 years
Secondary outcomes:
measure: Part 1a: ORR
timeFrame: maximum 2 years
measure: Part 1a: Disease Control Rate, DCR
timeFrame: maximum 2 years
measure: Part 1a: Duration of Response, DOR
timeFrame: maximum 2 years
measure: Part 1a: Duration of Disease Control, DDC
timeFrame: maximum 2 years
measure: Cmax
timeFrame: maximum 2 years
measure: Tmax
timeFrame: maximum 2 years
measure: AUC0-last
timeFrame: maximum 2 years
measure: AUC0-tau
timeFrame: maximum 2 years
measure: UC0-inf
timeFrame: maximum 2 years
measure: Vss
timeFrame: maximum 2 years
measure: CL
timeFrame: maximum 2 years
measure: t1/2
timeFrame: maximum 2 years
measure: Part 1a: Immunogenicity of HBM4003 and pembrolizumab
timeFrame: maximum 2 years
measure: Part 1b: Number of subjects experiencing at least one treatment-related AE
timeFrame: maximum 2 years
measure: Part 1b: DCR
timeFrame: maximum 2 years
measure: Part 1b: DOR
timeFrame: maximum 2 years
measure: Part 1b: DDC
timeFrame: maximum 2 years
measure: Part 1b: Overall survival (OS)
timeFrame: maximum 2 years
measure: Part 1b: Progression-free survival (PFS)
timeFrame: maximum 2 years
measure: Part 1b: Immunogenicity of HBM4003 and pembrolizumab
timeFrame: maximum 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun LU, Doctor
role: PRINCIPAL_INVESTIGATOR
References: