Solid Tumor Malignancies
Conditions
Brief summary
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of GKL-006Allo Injection in participants with advanced solid tumors.
Detailed description
This Phase 1 study will evaluate GKL-006Allo Injection in participants with advanced or metastatic solid tumors who have failed or are intolerant to standard therapy. The study includes single-dose and multiple-dose treatment, with a potential dose-expansion stage to further evaluate selected dose level according to protocol-specified criteria. The single-dose and multiple-dose stages are designed to characterize safety, tolerability, and biological activity across protocol-specified dose levels. Participants will receive GKL-006Allo Injection according to the study protocol and will undergo scheduled safety monitoring, tumor assessments, pharmacokinetic and pharmacodynamic sampling, and immunogenicity testing during treatment and follow-up.
Interventions
BIOLOGICALGKL-006Allo Injection
GKL-006Allo Injection is an allogeneic invariant natural killer T (iNKT) cell therapy. It will be administered according to the dose level, dosing schedule, and treatment stage specified in the protocol.
Sponsors
Beijing Gene Key Life Technology Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. Participants, investigators, and study personnel will be aware of the treatment administered.
Intervention model description
Participants will be assigned to sequential study stages, including a single-dose escalation stage, a multiple-dose treatment stage, and, if conducted, dose-expansion stages according to protocol-specified safety review and dose-escalation rules.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Able to understand and voluntarily sign the informed consent form. * Aged 18 to 75 years. * Histologically, cytologically or clinical confirmed unresectable locally advanced or metastatic solid tumor that has failed standard therapy. * At least one measurable tumor lesion during screening according to RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and life expectancy of at least 3 months. * Adequate hematologic and organ function. * Participants of childbearing potential must agree to use at least one medically accepted contraceptive method during study treatment and for 6 months after the end of study treatment. * Able to communicate with the investigator, comply with study visits, and understand and follow study requirements.
Exclusion criteria
* Recently received radical radiotherapy or other anti-tumor therapy. * Known hypersensitivity to any component of the study treatment. * Prior history or concurrent malignancy that has not been cured. * Active infection, known or suspected autoimmune disease. * Last anti-tumor treatment toxicity not yet recovered to suitable status. * Other organ dysfunction or situations deemed inappropriate by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) | From the first dose through the end of the DLT observation period, assessed up to 28 days. | Dose-limiting toxicities will be assessed according to protocol-defined DLT criteria. |
| Incidence and Severity of Adverse Events | From the first dose of study treatment until 28 days after the pointed dose of study treatment. The safety monitor will be continued until the end of the study, up to 18 months. | Safety will be assessed by the incidence and severity of adverse events, serious adverse events, laboratory abnormalities, electrocardiogram abnormalities, physical examination findings, and vital sign abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From the first dose of study treatment until disease progression or death from any cause, whichever occurs first, assessed up to 18 months. | Progression-free survival is defined as the time from the first dose of study treatment to the first documented disease progression or death from any cause, whichever occurs first, according to RECIST v1.1. |
| Overall Survival (OS) | From the first dose of study treatment until death from any cause, assessed up to 18 months. | Overall survival is defined as the time from the first dose of study treatment to death from any cause. |
| Change From Baseline in EORTC QLQ-C30 Scale Scores | Baseline and scheduled post-baseline assessments, up to 18 months. | Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores for each scale range from 0 to 100. Higher scores on the functional scales and global health status/quality-of-life scale indicate better functioning or quality of life. |
| Immunogenicity | From baseline through protocol-specified immunogenicity sampling time points, assessed up to 180 days. | GKL-006 Alloantibodies (ADA) and their titers, anti-GKL-006 Allo neutralizing antibodies (Nab) and their titers, anti-HLA antibodies, etc. will be tested. |
| Disease Control Rate (DCR) | From the first dose of study treatment through scheduled tumor assessments, assessed up to 18 months. | Disease control rate is defined as the proportion of participants with a best overall response of complete response, partial response, or stable disease according to RECIST v1.1. |
| Objective Response Rate (ORR) | From the first dose of study treatment through scheduled tumor assessments, assessed up to 18 months. | Objective response rate is defined as the proportion of participants with a best overall response of complete response or partial response according to RECIST v1.1. |
| Pharmacokinetic characterization of maximum observed plasma concentration (Cmax) | From 60 minutes before the first dose through 150 days. | Maximum observed plasma concentration of GKL-006 following intravenous administration according to protocol. |
| Pharmacokinetic characterization of time to maximum observed plasma concentration (Tmax) | From 60 minutes before the first dose through 150 days. | Time to reach the maximum observed plasma concentration of GKL-006 following intravenous administration. |
| Pharmacokinetic characterization of area under the plasma concentration-time curve (AUC) | From 60 minutes before the first dose through 150 days. | Area under the plasma concentration-time curve of GKL-006 following intravenous administration. |
| Pharmacokinetic characterization of terminal elimination half-life (t½) | From 60 minutes before the first dose through 150 days. | Terminal elimination half-life of GKL-006 calculated from plasma concentration-time data following intravenous administration. |
| Pharmacodynamic Biomarkers of NK cells | From 60 minutes before the first dose through 150 days. | Immune cell subsets |
| Pharmacodynamic Biomarkers of Peripheral blood TNF-α | From 60 minutes before the first dose through 150 days. | Immune-related cytokines |
| Pharmacodynamic Biomarkers of Peripheral blood IFN-γ | From 60 minutes before the first dose through 150 days. | Immune-related cytokines |
Countries
China
Contacts
CONTACTCancer Hospital Chinese Academy of Medical Sciences
PRINCIPAL_INVESTIGATORNing Li, MD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed