Advanced Solid Tumors
Conditions
Keywords
Engineered Red Blood Cells, Immunotherapy, Phase I, Solid Tumor, Allogeneic Engineered Red Blood Cell, uRBC
Brief summary
This is a multicenter, open-label, single-arm Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of allogeneic WTX-212C, an investigational allogeneic engineered red blood cell (RBC)-based product, in patients with advanced solid tumors who have failed standard therapies or have no available standard treatment options. The study consists of a dose-escalation phase using a 3+3 design followed by a dose-expansion phase. Participants will receive allogeneic WTX-212C via intravenous infusion. Tumor assessments will be performed every 6 weeks according to RECIST 1.1.
Detailed description
This Phase I study aims to characterize the safety profile, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics, immunogenicity, and preliminary efficacy of allogeneic WTX-212C in patients with advanced solid tumors. The dose-escalation phase will follow a traditional 3+3 design with predefined dose levels. The dose-expansion phase will further evaluate safety, PK, and antitumor activity at selected dose levels. Exploratory analyses will include immune profiling, tumor microenvironment assessment, and evaluation of biomarkers such as PD-1/PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI) status.
Interventions
DRUGallogeneic WTX-212C
allogeneic WTX-212C is an investigational allogeneic engineered red blood cell-based injectable product administered intravenously.
Sponsors
Zhejiang Provincial People's Hospital
Westlake Therapeutics
First People's Hospital of Hangzhou
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a sequential assignment study consisting of a dose-escalation phase followed by a dose-expansion phase. The dose-escalation phase will follow a standard 3+3 design with predefined dose levels. Dose escalation decisions will be based on the occurrence of dose-limiting toxicities (DLTs) observed during the first treatment cycle. Upon identification of a tolerable dose level, one or more dose-expansion cohorts may be opened to further characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of allogeneic WTX-212C.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years * Histologically or cytologically confirmed advanced solid tumors * At least one measurable lesion per RECIST 1.1 * ECOG performance status ≤1 * Adequate organ function * Life expectancy ≥12 weeks
Exclusion criteria
* Uncontrolled serious medical conditions * Active or uncontrolled infections * Symptomatic or unstable CNS metastases * History of severe hypersensitivity to biologic agents * Autoimmune diseases requiring systemic treatment * Prior severe immune-related adverse events * Conditions affecting red blood cell integrity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | Within 21 days after the first dose | Incidence of Dose-Limiting Toxicities (DLTs) |
| Incidence and Severity of Treatment-Related Adverse Events (TRAEs) | Up to 12 months | Incidence of Dose-Limiting Toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Within 21 days after the first dose | MTD is defined as the highest dose level at which no more than 1 out of 6 participants experiences a dose-limiting toxicity (DLT) during the first treatment cycle, based on a standard 3+3 dose-escalation design. |
| Pharmacokinetic Parameters (Cmax) | From first dose up to 12 months | Plasma pharmacokinetic parameters of allogeneic WTX-212C, including maximum observed concentration (Cmax）will be estimated using non-compartmental analysis methods. |
| Objective Response Rate (ORR) | Up to 12 months | ORR is defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria, based on investigator assessment. |
| Disease Control Rate (DCR) | Up to 12 months | DCR is defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST version 1.1 criteria. |
| Progression-Free Survival (PFS) | Up to 12 months | PFS is defined as the time from the first dose of allogeneic WTX-212C to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. |
| Incidence of Anti-Drug Antibodies (ADA) | From baseline up to 12 months | The incidence of anti-drug antibodies (ADA) against allogeneic WTX-212C will be assessed using validated immunoassays. |
| Pharmacokinetic Parameters (AUC) | From first dose up to 12 months | Plasma pharmacokinetic parameters of allogeneic WTX-212C，area under the concentration-time curve (AUC), will be estimated using non-compartmental analysis methods. |
| Pharmacokinetic Parameters (Tmax) | From first dose up to 12 months | Plasma pharmacokinetic parameters of allogeneic WTX-212C, time to maximum concentration (Tmax) will be estimated using non-compartmental analysis methods. |
| Pharmacokinetic Parameters (T1/2) | From first dose up to 12 months | Plasma pharmacokinetic parameters of allogeneic WTX-212C, and terminal elimination half-life (t1/2) will be estimated using non-compartmental analysis methods. |
Countries
China
Contacts
CONTACTYang Liu, PhD
Outcome results
None listed