Solid Tumor Malignancies
Conditions
Keywords
GO321, Solid tumor malignancies, Oncolytic Viral Therapy
Brief summary
The goal of this clinical trial is to learn about the safety and tolerability of GO321 recombinant oncolytic virus injection, and if GO321 recombinant oncolytic virus injection works to treat advanced solid tumors in adults whose cancers have progressed after standard-of-care therapy. It will also learn about the pharmacokinetic features, viral shedding, immunogenicity of GO321, immune markers, and genomic and proteomic changes in patients. The main questions it aims to answer are: What safety issues and tolerability limitations do participants experience when receiving GO321 via intratumoral or intracavitary injection? Does GO321 have preliminary anti-tumor efficacy against advanced solid tumors resistant to standard treatment? What changes take place in viral distribution, viral shedding, immunity, blood immune markers, tumor or blood genomics and proteomics after GO321 administration? Researchers will assess different doses and dosing schedules of GO321 given by intratumoral or intracavitary injection across two study phases to find a suitable administration dose and regimen and verify the study endpoints. Participants will: Receive either a single injection of GO321 at different dose levels (in Part 1) or repeated GO321 injections at the recommended Phase 2 dose (in Part 2) by intratumoral or intracavitary routes; Complete scheduled hospital visits to undergo laboratory tests, imaging examinations and biological sample collection; Have their safety indicators, anti-tumor response, viral parameters, immune indicators and molecular profiles tracked throughout the study.
Detailed description
This study adopts a single-arm, open-label, dose-escalation design to investigate the safety, tolerability, and preliminary efficacy of GO321 recombinant oncolytic virus injection via intratumoral or intracavitary administration in patients with advanced solid tumors progressing after standard-of-care (SOC) therapy. The trial consists of two parts: a single-dose escalation phase and a multiple-dose expansion phase. Part 1: Single-Dose Escalation The primary Objectives: To evaluate the safety and tolerability of single intratumoral or intracavitary GO321 injection at varying dose levels in SOC-refractory advanced solid tumor patients, and identify the Recommended Dose (RD) of intratumoral/intracavitary administration for Phase 2.. The secondary Objectives: 1) To evaluate the pharmacokinetic (PK) profile and viral shedding of GO321 following single intratumoral/intracavitary administration; 2) To evaluate the preliminary efficacy of GO321; 3) To evaluate the immunogenicity of GO321; 4) To monitor peripheral blood pharmacodynamic immunological markers related to T-lymphocyte subsets and changes in plasma cytokines (as applicable). The exploratory Objectives: To assess changes in genomic or proteomic profiles in tumor tissue or peripheral blood (as applicable). Part 2: Multiple-Dose Expansion The Main Objectives is to evaluate the safety and tolerability of multiple intratumoral (or intracavitary) injections of GO321 at the RD level in SOC-refractory advanced solid tumor patients, and determine the optimal dosing regimen. The secondary Objectives: 1) To evaluate the pharmacokinetic (PK) profile and viral shedding of GO321 following multiple intratumoral/intracavitary administrations; 2) To evaluate the preliminary efficacy of GO321; 3) To evaluate the immunogenicity of GO321; 4) To monitor peripheral blood pharmacodynamic immunological markers related to T-lymphocyte subsets and changes in plasma cytokines (as applicable). The exploratory Objectives: To assess changes in genomic or proteomic profiles in tumor tissue or peripheral blood (as applicable).
Interventions
DRUGGO321
Part 1: 3+3 Single-Dose Escalation Phase： This phase adopts a standard 3+3 dose-escalation design. GO321 is administered via intratumoral or intracavitary single injection, with the dose escalating progressively within the range of 3.0E+07 PFU to 1.0E+09 PFU. Each dose cohort will enroll 3 subjects, and all enrolled subjects will receive a single initial administration of the study drug. Part 2: Multiple-Dose Expansion Phase： This expansion phase is conducted at the recommended dose (RD) level, aiming to explore the preliminary anti-tumor efficacy of GO321 in specific tumor types. A total of 9 subjects with specific tumor types will be enrolled in this cohort. GO321 is administered via intratumoral or intracavitary injection on a once-weekly (QW) or once-every-two-weeks (Q2W) dosing schedule.
Sponsors
GeneSail Biotech (Shanghai) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-arm, non-randomized study which comprises two parts: * Part 1: A 3+3 single-dose escalation phase to determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and Recommended Dose (RD) of the investigational product. * Part 2: A multiple-dose expansion phase at the RP2D level to explore preliminary efficacy in specific tumor types.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years old and above, regardless of gender. * Histologically or cytologically confirmed advanced malignant solid tumors that are refractory to or have failed standard therapy (including disease progression and/or intolerance to toxicity), or for which no standard therapy is available. * For patients with malignant ascites secondary to malignant tumors (e.g., ovarian cancer, gastrointestinal solid malignancies) who are planned to receive intracavitary injection, the following criteria must be met: * a. Malignant ascites is determined by the investigator to be caused by cancer cell dissemination, and not complicated by ascites due to other etiologies; * b. Recurrence of ≥ Grade 2 ascites within 4 weeks after at least one prior local therapy (including paracentesis, intraperitoneal chemotherapy, peritoneovenous shunt, hyperthermic intraperitoneal chemotherapy, etc.); * c. Large-volume peritoneal effusion confirmed by computed tomography (CT) or ultrasound, with a clinical indication for local therapeutic intervention targeting the ascites. * Patients scheduled for intratumoral injection must meet the following requirements: At least one evaluable lesion confirmed by local imaging per RECIST v1.1 that is amenable to intratumoral injection. A lesion suitable for intratumoral injection (with or without CT/ultrasound guidance) is defined as a palpable mass or a mass visible by CT/ultrasound that can be injected under CT/ultrasound guidance, located in the skin, subcutaneous tissue, or deep-seated regions, with a longest diameter ≥ 1.0 cm (or short axis ≥ 1.5 cm if a lymph node), and deemed appropriate for intratumoral injection by the investigator. If the injection site has been previously irradiated, eligibility may be considered after discussion with the sponsor. * Eastern Cooperative Oncology Group (ECOG) score ≤2. * Expected survival time ≥3 months. * Study participants had adequate organ function at screening/baseline, and the laboratory indicators met the following criteria: * a. Hematopoietic system (no previous blood transfusion or hematopoietic stimulating factor therapy within 14 days) : absolute neutrophil count (ANC) ≥1.5E+09/L; Hemoglobin (Hgb) ≥90g/L; Platelet count (Plt) ≥75E+09/L. * b. Liver function: serum total bilirubin (TBIL) ≤1.5×ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN, with liver metastasis TBIL≤3×ULN, ALT and AST≤5×ULN; Serum albumin ≥2.8 g/dL (Subjects may receive albumin supplementation to meet these laboratory criteria). * c. Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (according to Cockroft-Gault formula) \>50mL/min. * d. Coagulation: international normalized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN. * Study participants were willing and able to comply with protocol requirements for the duration of the trial, including but not limited to receiving treatment, use effective contraception throughout trial participation and for 6 months after the last study drug administration, and undergoing regular follow-up and examinations.
Exclusion criteria
* Female participants who were pregnant or lactating. * Presence of another malignancy within the previous 2 years, except for cancers with a low risk of metastasis and death (5-year survival rate, \>90%), such as adequately treated basal-cell or squamous-cell skin cancer or carcinoma in situ of the cervix and other cancers in situ. * Adverse events from prior anti-tumor therapy have not recovered to Grade ≤ 1 per CTCAE v6.0, or to the levels specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs | Up to 6 months after the last GO321 administration | Adverse events (AEs) will be graded according to the CTCAE Version 6.0 published by the U.S. National Cancer Institute. |
| SAEs | Up to 6 months after the last GO321 administration. | Serious Adverse events (SAEs) will be graded according to the CTCAE Version 6.0 published by the U.S. National Cancer Institute. |
| DLT | within 28 days after the first GO321 administration. | The Dose-Limiting Toxicities (DLTs) assessed using the NCI CTCAE v6.0. |
| RD | Through study of Part 1 completion, an average of 9 months. | The Recommended Dose (RD) will be determined based on the integrated analysis of Part 1 (3+3 dose-escalation phase) results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics/Viral Shedding | Within 28 Days after the last GO321 administration | Concentrations of GO321 (viral genome copy numbers ) in blood, throat swab, urine, saliva, stool, and injection-site samples collected at various time points after a single dose (in part 1) or multiple dose (in part 2), and concentrations of GO321 expression products in peripheral blood. |
| ORR | Up to 5 years after the last GO321 administration. | Objective Response Rate (ORR)(Basd on the RECIST V1.1and iRECIST): The proportion of trial participants achieving best overall response of Complete Response (CR) or Partial Response (PR) (i.e., CR+PR) from the first dose administration until study withdrawal. |
| DCR | Up to 5 years after the last GO321 administration. | Disease control rate (Basd on the RECIST V1.1and iRECIST): The proportion of trial participants achieving disease response or stable disease after treatment |
| PFS | Up to 5 years after the last GO321 administration. | Progression-Free Survival (PFS)(Basd on the RECIST V1.1and iRECIST): The time from the first dose administration to Progressive Disease (PD) or death from any cause, whichever occurs earlier |
| DOR | Up to 5 years after the last GO321 administration. | Duration of Response (DOR)(Basd on the RECIST V1.1and iRECIST): The time from the first documentation of CR or PR to PD or death from any cause, whichever occurs earlier. |
| OS | Up to 5 years after the last GO321 administration. | Overall Survival (OS)(Basd on the RECIST V1.1 and iRECIST): Time interval from the date of first study drug administration to the date of death due to any cause. |
| Pharmacodynamics/Immunological Markers | Within 28 days after the last GO321 administration | eripheral blood T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, CD19+, etc., as applicable); plasma cytokines (IL-2, IFN-γ, granzyme B, perforin, IL-10, TGF-β1, etc., as applicable) |
| Immunogenicity indicators | Within 28 days after the last GO321 administration. | Anti-GO321 antibodies, anti-GO321 expression product antibodies, and/or neutralizing antibodies (if applicable); |
Countries
China
Contacts
CONTACTNing Li, Doctor
Outcome results
None listed