A Phase I Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of GO306 Recombinant Oncolytic Vaccinia Virus Injection in Patients With Advanced Refractory Solid Tumors.
A Phase I Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of GO306 Recombinant Oncolytic Vaccinia Virus Injection in Patients With Advanced Refractory Solid Tumors.
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.
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.
Part 2 Multiple dose exploration phase.
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:
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:
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:
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/exclusion criteria (except for alopecia, hyperpigmentation and other adverse events judged by the investigator as no safety risk). Subjects with chronic grade 2 toxicity were eligible after discussion with the sponsor if they were asymptomatic or adequately controlled with stable medications.
Antineoplastic therapy, including chemotherapy, radiotherapy, biotherapy, endocrine therapy, or immunotherapy, was received within 4 weeks or five half-lived periods (whichever was less) before the first use of the investigational drug, except for the following drugs: nitrosourea or mitomycin C within 6 weeks before the first use of the investigational drug; For oral fluorouracil and small molecule targeted drugs, 2 weeks before the first use of the investigational drug or within the 5 half-lives of the drug, whichever is longer; The Chinese herbal medicine or Chinese patent medicine with anti-tumor indication was within 2 weeks before the first use of the investigational drug.
Presence of any of the following infections or diseases:
Have a history of active autoimmune disease requiring systemic therapy such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or have been receiving long-term systemic steroids (prednisone >10mg/ day or equivalent dose of the same drug) or any other form of immunosuppressive therapy within 14 days before the first use of the investigational drug. Patients with clinically stable autoimmune thyroid disease were excluded. The patients were treated with topical and inhaled corticosteroids, such as ocular, intra-articular, nasal, etc. Short-term use of glucocorticoids (not more than 3 days) for prophylaxis (e.g., to prevent contrast allergy); Physiological doses of hormone replacement therapy.
Received allogeneic tissue or solid organ transplantation.
A history of severe cardiovascular and cerebrovascular disease, including but not limited to:
Patients with grade 3 or above bleeding events in the previous 6 months; Or patients with > grade 2 bleeding, hemangioma/vascular malformation, tumor stroke, tumor invasion of blood vessels, active gastrointestinal ulcer, and esophageal varices, who were judged by the investigators to have a significant risk of bleeding.
A history of severe skin disease requiring systemic treatment within the previous 2 years, such as eczema, atopic dermatitis, burns, seborrheic dermatitis, psoriasis, severe acne, etc.
Patients with severe allergy or hypersensitivity reaction after using any drug or biological product in the past.
Anticoagulants or antiplatelet drugs should be used before intratumoral injection and should not be interrupted, including aspirin within 7 days before injection; Coumarin that cannot be stopped within 7 days before injection; Direct thrombin inhibitors (e.g., dabigatran) or direct factor Xa inhibitors (e.g., rivaroxaban, apixaban and endoixaban) that cannot be stopped within 4 days before injection; "Low-molecular-weight heparin (e.g., low-molecular-weight heparin [LMWH]), which cannot be discontinued within 24 hours before injection, and unfractionated heparin (e.g., unfractionated heparin [UFH]), which cannot be discontinued more than 4 hours before injection."
Use of systemic immunomodulatory drugs within 14 days before the first use of the investigational drug, including but not limited to thymosin, IL-2, IFN, etc.
Other circumstances requiring systemic anti-infective treatment within 4 weeks prior to the first administration of the investigational product, including but not limited to hospitalization for infectious complications, bacteremia, severe pneumonia, or active tuberculosis.
Within 4 weeks before the first use of the investigational drug: receiving other unmarketed investigational drugs or treatments, and receiving live vaccines or live attenuated vaccines.
Subjects who had undergone major surgery requiring hospitalization within 4 weeks before the first use of the investigational drug, or who were expected to undergo major surgery during the trial.
Concomitant use of sensitive substrate drugs metabolized by CYP450 enzymes with a narrow therapeutic window that cannot be stopped within the first 5 half-lives of the investigational drug is recommended after discussion with the sponsor.
Any known mental illness or substance abuse that may interfere with the subject's ability to cooperate with the trial.
According to the evaluation of the investigators, the treatment risks are high, including but not limited to the high risk of bleeding, possible damage to the surrounding important tissue structures, the risk of shock caused by dizzy with blood and needles, and the risk of aggravating local infection.
If the participant plans to participate in another clinical trial during the trial period, plans to leave the trial site, or otherwise is not suitable for participation in the trial as assessed by the investigator.
shizhenrui@genesailbiotech.com+86 21 20975454-1081
Hefei, Anhui, China