Solid Tumor Malignancies
Conditions
Keywords
GO306, Solid tumor malignancies, Oncolytic Viral Therapy
Brief summary
This study employs a single-arm, open-label, non-randomized, dose-escalation design to investigate the safety, tolerability, and efficacy of GO306 Recombinant Oncolytic Vaccinia Virus Injection. * Part 1: Utilizes the 3+3 design principle to evaluate the safety and tolerability of a single administration of GO306 at different dose levels. The primary goal is to determine the Maximum Tolerated Dose (MTD), providing the basis for selecting the Recommended Phase 2 Dose (RP2D). * Part 2: Evaluates the safety and tolerability of repeated intratumoral (IT) or intracavitary administrations of GO306 in patients with specific tumor types.
Detailed description
This study employs a single-arm, open-label, non-randomized, dose-escalation design to investigate the safety, tolerability, and efficacy of GO306 Recombinant Oncolytic Vaccinia Virus Injection. The study has two parts. * Part 1 is a single-dose escalation phase. * The Main Objectives of part 1 is to evaluate the safety and tolerability of single intratumoral injection/intracavitary administration of GO306 at different dose levels in patients with advanced solid tumors who failed to respond to standard treatment, and explore the maximum tolerated dose (MTD), so as to provide a basis for the recommended dose in the second stage. * The secondary objectives of Part 1 is 1) To evaluate the pharmacokinetics (PK) and viral shedding of GO306 after single intratumoral injection/intracavitary administration; 2) evaluate the preliminary efficacy of a single dose of GO306; 3) To monitor the changes of immunological parameters related to GO306 pharmacodynamics. * The exploratory objectives of Part 1 is to correlation between PD-L1 expression in tumor tissue, microsatellite instability (MSI), tumor mutation burden (TMB) and efficacy (if applicable); * Part 2 Multiple dose exploration phase. * The primary objective of Part 2 is to evaluate the safety and tolerability of multiple intratumoral injection/intracavitary administration of GO306 in patients with specific tumors and to determine the optimal dosing regimen. * The secondary objectives of Part 2 is 1) To evaluate the pharmacokinetics (PK) and viral shedding of GO306 after multiple intratumoral injections/intracavitary administration; 2) evaluate the preliminary efficacy of multiple doses of GO306; 3) evaluate the immunogenicity of GO306; 4) To monitor the changes of immunological indicators related to GO306 pharmacodynamics. * The exploratory objectives of Part 2 is to correlation between PD-L1 expression in tumor tissue, microsatellite instability (MSI), tumor mutation burden (TMB) and efficacy (if applicable).
Interventions
DRUGGO306
Part 1: A 3+3 single-dose escalation phase: Low-dose cohort: 3.0E+07 PFU; Intratumoral or intracavitary injection of GO306; Cohort Size: 3 subjects; Dosing Schedule: Single initial administration. Medium-dose cohort: 3.0E+08 PFU; Intratumoral or intracavitary injection of GO306; Cohort Size: 3 subjects; Dosing Schedule: Single initial administration. High-dose cohort: 1.0E+09 PFU; Intratumoral or intracavitary injection of GO306; Cohort Size: 3 subjects; Dosing Schedule: Single initial administration. Part 2: A multiple-dose expansion phase at the RP2D level to explore preliminary efficacy in specific tumor type: RP2D; Intratumoral or intracavitary injection of GO306; Cohort Size: 20 subjects in specific tumor type; Dosing Schedule: QW or Q2W administration.
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 Phase II Dose (RP2D) 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. * Patients with histologically or cytologically confirmed advanced malignant solid tumors, including but not limited to breast cancer, bladder urothelial cancer, colorectal cancer, renal cancer, ovarian epithelial cancer, and neuroendocrine tumors, who have no response or failure to standard treatment (including disease progression and/or intolerable side effects), or no standard treatment. Examples are as follows: * a. Histologically or cytologically confirmed unresectable or metastatic bladder urothelial carcinoma: failure to or intolerance to prior platinum-based chemotherapy and PD-1/PD-L1 inhibitors or no available standard treatment options for unresectable or metastatic disease. * b. Patients with histologically or cytologically confirmed recurrent ovarian cancer with malignant ascites who have received at least one previous line of platinum-based chemotherapy-based therapy and no available standard treatment options, and those with germline or somatic BRCA mutations who failed or did not tolerate PARP inhibitors. * c. Histologically or cytologically confirmed unresectable or metastatic colorectal cancer with liver metastases: failure or intolerance to prior oxaliplatin, fluorouracil, and irinotecan based therapy (or PD-1/PD-L1 inhibitors if the patient is MSI-H/dMMR) or no standard treatment options are available. * d. Patients with histologically or cytologically confirmed unresectable or metastatic clear-cell renal carcinoma with prior failure to, or intolerance to, Tkis and PD-1/PD-L1 inhibitors or no available standard treatment options for unresectable or metastatic clear-cell renal carcinoma. * e. Histologically or cytologically confirmed, locally advanced or metastatic triple-negative breast cancer: failure to or intolerance to at least one previous line of standard chemotherapy, which must include a taxane (e.g., paclitaxel, docetaxel), or no standard treatment options available. * f. For patients with neuroendocrine tumors, one of the following criteria must be met: * (1) Patients with histologically confirmed advanced stage (inoperable locally advanced or distant metastasis) with Ki-67≥55% in G3 NET and NEC (including mixed neuroendocrine and non-neuroendocrine tumors \[at least 30% neuroendocrine carcinoma component\], excluding small cell lung cancer and Meckel cell carcinoma) : They have failed or are intolerant to at least one previous line of standard chemotherapy (EP or EC), or no standard treatment options are available. * (2) Histologically confirmed advanced NET G3 patients (unresectable locally advanced or distant metastasis) and atypical pulmonary and mediastinal carcinoid patients: patients who had received at least second-line standard treatment failed or could not tolerate it, and the treatment regimen must include CAPTEM regimen or no available standard treatment regimen. * g. Histologically or cytologically confirmed advanced solid tumors (other than the above, e.g., soft tissue sarcoma, etc.) : documented disease progression or intolerance during or after receiving previous standard therapy, or no standard treatment options are available. * Patients with ovarian cancer and solid malignant tumors of the digestive tract with malignant ascites who plan intracavitary injection should meet the following requirements: * a. Malignant ascites was pathologically diagnosed as caused by the spread of cancer cells. * b. Grade ≥2 ascites recurred within 4 weeks after receiving at least one local treatment (including paracentesis, intraperitoneal chemotherapy, intraperitoneal venous shunt, hyperthermic intraperitoneal perfusion, etc.). * c. Massive peritoneal effusion confirmed by computed tomography (CT) or B-ultrasound, which clinically requires local treatment for peritoneal effusion. * At least one lesion that could be evaluated, as confirmed by local imaging, according to RECIST 1.1 criteria. Intratumoral injectable lesion, with or without CT/ ultrasound guidance, was defined as a palpable or CT/ ultrasound visible skin, subcutaneous, or deep mass with a major diameter ≥1.5cm (in the case of a lymph node, a short diameter ≥1.5cm) amenable to CT/ ultrasound guidance for intratumoral injection, as judged by the investigator. The injection site was required to have not been treated with radiation. * Eastern Cooperative Oncology Group (ECOG) score ≤2. * Expected survival time ≥3 months. * The subjects had adequate organ function at the baseline of the screening period, 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) ≥1.5×109/L; Hemoglobin (Hgb) ≥90g/L; Platelet count (Plt) ≥75×109/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 could use albumin to meet 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. * Participants were willing and able to comply with protocol requirements for the duration of the trial, including but not limited to receiving treatment, using effective contraception (for 3 months after dose), and undergoing regular follow-up and examinations.
Exclusion criteria
* Female subjects who were pregnant or lactating. * Patients who had received a diagnosis 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. * The adverse effects of previous antitumor treatment have not returned to CTCAE v5.0 grade 1, baseline or lower, or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs | Within 6 Months After the Last Treatment | Adverse events (AEs) will be graded according to the CTCAE Version 5.0 published by the U.S. National Cancer Institute. |
| SAEs | Within 6 months after the last treatment. | Severe Adverse events (SAEs) will be graded according to the CTCAE Version 5.0 published by the U.S. National Cancer Institute. |
| DLT | Up to 21 days from the first GO306 injection. | The Dose-Limiting Toxicities (DLTs) assessed using the NCI CTCAE v5.0. |
| MTD | Up to 21 days from the first GO306 injection. | The maximum tolerated dose (MTD) of GO306 will be defined based on the DLT |
| RP2D | Through the Part 1 of this study, an average of 4 months | The Recommended Phase II Dose (RP2D) will be determined based on the integrated analysis of Part 1 (3+3 dose-escalation phase) results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics/immunological indicators | In Part 1&2: Within 28 Days After the Last Dose | Including but not limited to: peripheral blood T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, CD19+, etc.), plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-α, IFN-γ, TNF-α, etc.) |
| Pharmacokinetics/viral shedding indicators | Part 1&2: Within 28 Days After the Last Dose | GO306 concentration (viral genome copy number) in blood, throat swabs, urine, saliva, feces, and injection site samples at different time points after a single dose, and the concentration of GO306 expression products in serum |
| Immunogenicity indicators | Part 1&2: Within 6 Months After the Last Dose | Anti-GO306 antibodies, and antibodies against GO306 expression products. |
| OS | Up to 5 years after the last treatment. | Overall Survival (OS)(Basd on the RECIST V1.1): Time interval from the date of first study drug administration to the date of death due to any cause. |
| PFS | Up to 5 years after the last treatment. | Progression-Free Survival (PFS)(Basd on the RECIST V1.1): Time from first dose to the earlier occurrence of disease progression per RECIST 1.1 or death from any cause. |
| ORR | Up to 5 years after the last treatment. | Objective Response Rate (ORR)(Basd on the RECIST V1.1): Proportion of subjects achieving a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST 1.1, assessed from first dose until treatment discontinuation. |
| DOR | Up to 5 years after the last treatment. | Duration of Response (DOR)(Basd on the RECIST V1.1): Time from the first documented CR or PR until PD or death from any cause, whichever occurs first, as assessed per RECIST 1.1 criteria. |
Countries
China
Contacts
Primary ContactZhenrui Shi
Outcome results
None listed