solid tumor
Conditions
Sponsors
Affiliated Cancer Hospital of Shandong First Medical University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. According to the investigator's judgment, the subject is capable of understanding and complying with the protocol requirements 2. Subject signs and dates written informed consent and any required privacy authorization prior to the commencement of any study procedure. 3. Sign a written ICF voluntarily and be at least 18 years old at the time of signing the ICF, regardless of gender. 4. Dose escalation stage: Subjects with histologically or cytologically confirmed advanced malignant solid tumors (including but not limited to ovarian cancer, TNBC, NSCLC, head and neck cancer, etc.), subjects who have failed standard treatment, or subjects who have no standard treatment options, or subjects who are not eligible for standard treatment at this stage. Subjects with certain known specific mutations or genetic abnormalities (e.g. EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS) must have previously received standard treatment for the target (based on the latest local guideline recommendations), Subjects are excluded if the investigator determines that standard treatment is not applicable, the benefit is limited, or intolerance (the cause of intolerance should be documented). Subjects with refractory PD-1 who have received anti-PD-1 standard therapy, or subjects who have not received anti-PD-1 therapy and do not have PD-1 standard therapy will be eligible for enrollment. Dose expansion phase: Cohort 1: Subjects with histologically or cytologically confirmed unresectable recurrent or metastatic head and neck squamous cell carcinoma. Subjects were required to have failed or been intolerant to previous anti-PD-1 monoclonal antibody and platinum-containing chemotherapy. Cohort 2: Histologically or cytologically confirmed subjects with advanced ovarian cancer who had received platinum-containing chemotherapy and were a) platinum-refractory (persistent disease after completing the first platinum-containing chemotherapy) and had failed at least the first platinum chemotherapy; b) Platinum resistance: (disease progression within 6 months of the last platinum-containing chemotherapy) failure in at least one second-line chemotherapy regimen. Subjects with platinum-resistant or refractory disease should receive bevacizumab in combination with chemotherapy and monotherapy maintenance. Subjects with serous or high-grade endometrial ovarian cancer, clear cell cancer, fallopian tube cancer, or primary peritoneal cancer with BRCA mutations should develop disease progression following maintenance therapy with PARP inhibitors. Cohort 3: Subjects with histologically or cytologically confirmed unresectable advanced or metastatic NSCLC. Subjects must have advanced disease after receiving standard therapy or be intolerant to clinically appropriate standard therapy. Participants had received at least first-line standard systemic therapy and had disease progression within the previous 6 months. NSCLC subjects with active EGFR mutations or ALK translocations who are expected to respond to available tyrosine kinase inhibitor therapy must have been treated with an applicable tyrosine kinase inhibitor prior to enrollment. Cohort 4: Dose escalation phase for other similarly sensitive tumor species, such as subjects with unresectable recurrent or metastatic TNBC. 5. Subjects with recurrent, refractory and locally advanced diseases were eligible for inclusion; However, subjects with curable and resectable diseases were not eligible to be enrolled. 6. Subjects had injectable tumo
Exclusion criteria
Exclusion criteria: 1. Subjects received chemotherapy or antibody therapy within 21 days prior to study day 1 and molecular targeted therapy, hormone therapy, therapeutic or palliative radiotherapy within 14 days prior to study day 1. 2. The subjects had systemic diseases that were not under stable control after treatment, such as diabetes mellitus, severe organic cardiovascular and cerebrovascular diseases, cardiac insufficiency, hypertension, heart block above grade II, myocardial infarction within the past 6 months, or cerebral infarction within the past 6 months, etc. 3. The maximum diameter of the lesion for injection is >100 mm. 4. The subject has an uncontrolled infectious disease, active hepatitis B (positive anti-hepatitis B core [HBc] antibody and hepatitis B virus [HBV]-DNA> Center detection limit [LLOD] within the previous 6 months); Active hepatitis C (positive for antibodies against hepatitis C virus [HCV] and HCV RNA load >LLOD within the previous 6 months); Positive antibodies against human immunodeficiency virus (HIV) -1 or HIV-2 and CD4+ T cells =300 /uL within the previous 3 months. 5. Subject had an uncontrolled = grade 3 active infection with significant clinical relevance according to CTCAE (Common Terminology Standard for Adverse Events) v5.0. 6. Subjects with other active malignancies within the previous 5 years. Subjects who have been completely cured and do not require follow-up treatment are excluded, and subjects whose malignant tumors are within the indications are excluded. 7. Subjects have tumors located at a high risk (including in the mucosal area, or near the airway, large blood vessels, or spinal cord) that may lead to occlusion or compression by tumor enlargement, or erosion of major blood vessels by necrosis, or enveloping major vascular structures (such as the carotid artery), adjacent to important neurovascular structures. Or other tumors deemed unsuitable for intratumoral injection. 8. Subjects had or had a history of an active autoimmune disease with the potential for recurrence, such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, or Wegener's granulomatosis, but subjects were admitted with: autoimmune hypothyroidism requiring hormone replacement therapy; Skin conditions that do not require systemic treatment (e.g. eczema, a rash that accounts for less than 10% of the body surface). 9. The subject is allergic to any component of the investigational drug, immunotherapy, or related drug. 10. People with organ dysfunction. Cardiovascular system: History or findings of congestive heart failure at NYHA level III or above; Or hypertension controlled by standard therapy (systolic blood pressure of 150mmHg and diastolic blood pressure of 90 mmHg), and a history of myocarditis or myocardial infarction within the past year; Urinary system: proteinuria grade 3; Pulmonary system: a history of pneumonia (non-infectious) requiring steroid treatment, or a history of pneumonia present; Central nervous system: symptomatic metastasis, active bleeding, thrombotic disease requiring treatment. Subjects with asymptomatic and stable brain metastases were eligible for inclusion. 11. Subjects received a systemic corticosteroid (equivalent to >10 mg prednisone/day) for 14 days prior to enrollment or during the study period. Subjects were eligible for inclusion in the cohort with topical or inhaled corticosteroid use, or short-term (=7 days) corticosteroid use for the prevent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and characteristics of adverse events/serious adverse events;Incidence and characteristics of dose-limiting toxicity;Maximum tolerable dose;Pharmacokinetic indicators;Pharmacodynamic indicators;Indicators of immunogenicity; | — |
Countries
China
Contacts
Public ContactYanqiu Liu
Affiliated Cancer Hospital of Shandong First Medical University
Outcome results
None listed