JY016 Injection in Patients With Advanced Solid Tumors Expressing EGFR

Official title

A Phase I/II Clinical Study on the Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of JY016 Injection in Patients With Advanced Solid Tumors Expressing EGFR

Overview

This study is a single-arm, open-label, multi-center Phase I/II clinical trial, consisting of Part A: the Phase I dose escalation stage, and Part B: the Phase II expansion stage. The objective of the Phase I dose escalation stage is to evaluate the safety, pharmacokinetic characteristics, and preliminary efficacy of JY016 injection in patients with advanced solid tumors expressing EGFR (immunohistochemistry 1+, 2+, or 3+). In the Phase II stage, the efficacy of JY016 in pancreatic cancer, non-small cell lung cancer, esophageal cancer, colorectal cancer, and squamous cell carcinoma of the head and neck with EGFR expression will be further evaluated.

Interventions

• Drug JY016
  0.08μg/kg\~30μg/kg,QW

Primary outcome measures

• MTD [Time frame: from baseline up to 4 weeks]
• Incidence of AEs [Time frame: through study completion, an average of 1 year]

Secondary outcome measures (2)

• Cmax [Time frame: from baseline up to 4 weeks]
• ORR [Time frame: From date of enrollment until the date of first documented progression, assessed up to 24 months]

Eligibility criteria

Inclusion criteria

• 1\. Age ≥ 18 years and ≤ 75 years;
• 2\. Tumor diagnosis and previous anti-tumor treatment: Phase I dose escalation stage: Subjects with advanced solid tumors with EGFR expression (immunohistochemistry 1+, 2+ or 3+) who have undergone standard treatment failure, or lack effective treatment options, or are unable to tolerate standard treatment, diagnosed by histological or cytological methods; Phase II expansion stage: Several tumor types with confirmed EGFR expression (initially determined as immunohistochemistry 1+, 2+ or 3+, and can be adjusted based on the exploratory results of EGFR expression in the dose escalation stage) confirmed by the central laboratory.
• 3\. ECOG physical condition score is 0-1 point;
• 4\. Expected survival exceeds 12 weeks;
• 5\. The bone marrow reserve and organ function levels must meet the following requirements 4 weeks before the first administration:(1) Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; hemoglobin ≥ 90 g/L; (no blood transfusion or hematopoietic stimulating factor treatment within 14 days before the first administration);(2) Liver and kidney function: serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if there is liver metastasis, ALT and AST ≤ 5 × ULN; creatinine clearance rate ≥ 50 mL/min (using the Cockcroft-Gault formula) or serum creatinine ≤ 1.5 × ULN;(3) Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal; international normalized ratio (INR) ≤ 1.5 × ULN;(4) Cardiac function: cardiac ultrasound examination, left ventricular ejection fraction ≥ 50%; QT interval (QTcF) ≤ 450 milliseconds.
• 6\. At least one measurable lesion defined by RECIST v1.1 must exist at the baseline period;
• 7\. Reproductive-capable subjects (male and female) must agree to use reliable contraceptive methods (hormonal or barrier methods or abstinence) with their partners during the trial period and for at least 3 months after the last administration; for pregnant women of childbearing age, a negative blood pregnancy test must be obtained within 14 days before the first use of the trial drug.
• 8.I have fully understood this study and voluntarily signed the informed consent form, willing and able to follow the research procedures.

Exclusion criteria

• 1\. The time interval between the last anti-tumor treatment and the first administration: for cytotoxic drugs and small molecule targeted drugs, ≤ 3 weeks; for large molecule monoclonal antibodies, ≤ 4 weeks; for radiotherapy (except for local radiotherapy for relieving pain) ≤ 4 weeks; for traditional Chinese medicine with anti-tumor indications approved by NMPA, ≤ 2 weeks;
• 2\. Known to be allergic to injectable JY016 or any of its excipient components; or having a history of allergy to drugs containing monoclonal components; other drug-induced liver toxicity or allergy history; or having a specific allergic reaction history (asthma, rubella, eczematous dermatitis); the subjects who have undergone previous anti-tumor treatment with central nervous system metastasis cancer, cancerous meningitis, or other central nervous system diseases or abnormalities;
• 3\. Have received targeted CD3 drug treatment before;
• 4\. Known to have central nervous system metastatic cancer, cancerous meningitis, or other central nervous system diseases or abnormalities;
• 5\. Human immunodeficiency virus (HIV) antibody positive, syphilis antibody positive or having other acquired or congenital immune deficiency diseases; active hepatitis C, antibody positive and HCV RNA test positive; active hepatitis B, for HBsAg positive, HBV DNA needs to be detected, and HBV DNA is higher than the upper limit of the normal value;
• 6\. Have received any anti-tumor treatment that was effective through T-cell recruitment therapy before, including but not limited to CAR-T and other in vitro cell therapies, CD3+ monoclonal antibodies, CD3+ dual antibodies, etc.;
• 7\. Have had a subject who experienced cytokine release syndrome (CRS) after any treatment;
• 8\. Have had anti-tumor treatment-related toxicity that has not been relieved to grade 1 or below (CTCAE v5.0) (excluding alopecia, pigmentation, and other toxicities determined by the investigator not affecting the safety of the study drug);
• 9\. Have other malignant tumors (excluding skin basal cell carcinoma and carcinoma in situ that underwent radical treatment and no disease recurrence within 5 years before screening);
• 10\. Have used other clinical trial test drugs within 4 weeks before the first administration of the test drug;
• 11\. Have used live virus vaccines within 4 weeks before the first administration of the test drug or during the expected study period, and within 4 weeks after the expected cessation of the study treatment;
• 12\. Have had active or requiring treatment bacterial, viral or fungal infections within 4 weeks before the first administration of the test drug;
• 13\. History of active tuberculosis;
• 14\. Have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• 15\. Have active autoimmune diseases (including but not limited to immune-related myocarditis, immune-related pneumonia, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, multiple sclerosis, vasculitis or glomerulonephritis, etc.) within 1 year of receiving systemic treatment;
• 16\. Have undergone major organ surgery (excluding biopsy and minimally invasive surgeries that have recovered well) or had significant trauma within 4 weeks before the first administration of the test drug, or need to undergo elective surgery during the study period;
• 17\. Have had severe non-healing wounds/ulcers/fractures within 4 weeks before the first administration of the test drug;
• 18\. Have a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: 1) Severe cardiac rhythm or conduction abnormalities; 2) Congestive heart failure (NYHA classification ≥ III); 3) Acute coronary syndrome, aortic dissection, stroke or other grade 3 or above cardiovascular events within 6 months before the first administration;
• 19\. Uncontrolled third space effusion (pleural effusion, pericardial effusion or abdominal effusion, etc.);
• 20\. Known to have a history of drug abuse;
• 21\. Pregnant or lactating women;
• 22.The investigator believes that the subject has other systemic diseases or other reasons that make them unsuitable to participate in this clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07510841 · BPL-JY016-ST-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗