Pancreatic Cancer
Conditions
Keywords
RASG12V, HLA, T-cell engager
Brief summary
ESSIGHT-HJG-ES502-01 is a dose-escalation study of ES502 in patients with advanced pancreatic cancer. The study will enroll patients with advanced, RAS G12V positive pancreatic cancer who have no effective treatment options available (HLA genotyping required).
Detailed description
The study will adopt the standard "3+3" design., with a first-in-human (FIH) dose of 20 μg administered once every four weeks (Q4W). Subsequent dosing frequency will be adjusted based on pharmacodynamics and pharmacokinetics data. The primary objectives of this study are to evaluate the safety and tolerability of ES502 and to determine its maximum tolerated dose (MTD). The secondary objectives are to evaluate its antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD).
Interventions
DRUGES502 Injection
Bispecific soluble HLA-DP restricted RASG12V specific T-cell receptor fused to anti-CD3 with Fc
Sponsors
Ruijin Hospital
Shanghai Essight Bio Co.,Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation will proceed through 4 predetermined dose levels following the traditional "3+3" trial design. The dose will be escalated sequentially from the starting level. The study may proceed to the next higher dose cohort following confirmation by the Safety Monitoring Committee (SMC) that all subjects in the current cohort have safely passed the 28-day dose-limiting toxicity (DLT) observation period after the first dose. The starting dose cohort will utilize an accelerated titration design with 1-6 subjects, followed by subsequent cohorts of 3-6 subjects each, for a total of 10-24 participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- To be enrolled in this study, participants must meet all of the following inclusion criteria: 1. Age ≥18 years, regardless of gender; 2. Available fresh or archived tumor tissue samples (within the past 5 years) for testing at screening; 3. Individuals with histologically or cytologically confirmed advanced solid tumors for whom no standard therapy exists, who are refractory to standard therapy, or who are deemed unsuitable for standard therapy by the investigator. Tumor types include but are not limited to: pancreatic cancer, colorectal cancer, non-small cell lung cancer, intrahepatic cholangiocarcinoma, gallbladder cancer, ovarian cancer, endometrial cancer, and intestinal cancer; 4. RAS G12V mutation (KRAS/NRAS/HRAS) and positivity for HLA-DPB1\*03:01, \*14:01, \*25:01, or \*104:01; 5. Individuals with at least one measurable lesion (defined per RECIST v1.1 as a lesion with the longest diameter ≥10 mm, or a lymph node with a short axis of ≥15 mm); lesions that have undergone radiotherapy or other local therapies are not considered target lesions unless they demonstrate clear progression; 6. ECOG score: 0-1; 7. Expected survival greater than 3 months; 8. Adequate hematological and organ function, as evidenced by the following laboratory tests (the individual must not have received a blood transfusion, long-acting EPO or long-acting G-CSF within 14 days before study treatment, or not have received short-acting EPO or short-acting G-CSF within 7 days before study treatment): 1) hematology: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (Hb) ≥90 g/L; 2) liver function test: both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN), total bilirubin (TBIL) ≤1.5 × ULN. Exceptions: liver metastasis, AST and/or ALT ≤5 × ULN; Gilbert's syndrome, TBIL ≤3 × ULN; pancreatic head cancer or biliary obstruction, TBIL ≤3 × ULN; 3) kidney function test: creatinine clearance (CrCL) ≥50 mL/min (by Cockcroft-Gault formula); 4) coagulation function test: activated partial thromboplastin time (APTT) ≤1.5 × ULN and international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN; 5) echocardiography: left ventricular ejection fraction (LVEF) ≥50%; eligibility for enrollment of individuals with out-of-range laboratory results should be determined at the investigator's discretion. 9. Women of childbearing potential who agree to use at least one medically recognized method for contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study treatment and for 1 year after the last treatment, and have a negative pregnancy test result at screening; 10. Prior antitumor treatment-related adverse events (AEs) (per NCI-CTCAE v6.0) have resolve to ≤ Grade 1 at screening, except for alopecia, Grade 2 hypothyroidism, and non-clinically significant or asymptomatic laboratory abnormalities; 11. Individuals who fully understand the informed consent information, agree to participate in this clinical study, and voluntarily sign the Informed Consent Form (ICF).
Exclusion criteria
\- To be enrolled in this study, participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of ES502 in subjects with advanced solid tumors | 2 years | DLT, and incidence and severity of adverse effects. |
| To determine the maximum tolerated dose (MTD) | 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary antitumor activity | 2 years | Objective response rate (ORR),% |
| To evaluate the immunogenicity of ES502 in subjects with advanced solid tumors | 2 years | Immunogenicity: Seropositivity rates of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) |
| Pharmacokinetic (PK) | 2 years | Maximum plasma concentration (Cmax), ng/mL |
Countries
China
Contacts
CONTACTChenlei Wen
CONTACTBaiyong Shen
STUDY_DIRECTORBaiyong Shen
Ruijin Hospital
Outcome results
None listed