A Study of Dose Escalation of ES502 in Patients With Advanced Pancreatic Cancer

NCT07649928 | Recruiting Early Phase 1

• 1 other identifier: ESSIGHT-HJG-ES502-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Pancreatic Cancer

Keywords

RASG12V; HLA; T-cell engager

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of ES502 in subjects with advanced solid tumors

  DLT, and incidence and severity of adverse effects.

  2 years

• To determine the maximum tolerated dose (MTD)

  2 years

Secondary Outcomes (13)

• Preliminary antitumor activity

  2 years

• Preliminary antitumor activity

  2 years

• Preliminary antitumor activity

  2 years

• Preliminary antitumor activity

  2 years

• Preliminary antitumor activity

  2 years

Other Outcomes (7)

• Pharmacodynamic (PD)

  2 years

• Pharmacodynamic (PD)

  2 years

• Pharmacodynamic (PD)

  2 years

Study Arms (1)

Dose escalation cohort

EXPERIMENTAL

A dose-escalation study will be conducted following the standard 3+3 design, with doses of 20, 60, 180, and 540 μg. A total of 10-24 subjects are planned to be enrolled. Depending on the subject's conditions (including but not limited to safety results, pharmacokinetic and pharmacodynamic data, etc.), and under the premise of ensuring subject safety, the investigator and/or ethics committee may decide to increase the dose or add new dose groups.

Drug: ES502 Injection

Interventions

ES502 Injection DRUG

Bispecific soluble HLA-DP restricted RASG12V specific T-cell receptor fused to anti-CD3 with Fc

Dose escalation cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, regardless of gender;
• Available fresh or archived tumor tissue samples (within the past 5 years) for testing at screening;
• 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;
• RAS G12V mutation (KRAS/NRAS/HRAS) and positivity for HLA-DPB1\*03:01, \*14:01, \*25:01, or \*104:01;
• 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;
• ECOG score: 0-1;
• Expected survival greater than 3 months;
• 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.
• 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;
• 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;
• Individuals who fully understand the informed consent information, agree to participate in this clinical study, and voluntarily sign the Informed Consent Form (ICF).

You may not qualify if:

• Individuals with the following tumors:
• Malignant tumors other than those under investigation in this study (except for cured thyroid cancer, skin basal cell carcinoma, or cervical carcinoma in situ) within the past 5 years;
• Meningeal metastases;
• Brain metastases, except for individuals who have received systematic and radical therapy (radiotherapy or surgery) for brain metastases, demonstrated radiologically stable disease for at least 4 weeks, discontinued systemic corticosteroids for more than 2 weeks, and remain asymptomatic.
• Individuals with the following conditions:
• Received prior targeted therapy targeting RAS-G12V within 4 weeks before the first dose, or within 5 half-lives of the therapeutic agent, whichever is longer;
• Participation in other clinical studies involving an investigational product within 4 weeks before the first dose;
• Use of systemic antitumor therapy (including but not limited to chemotherapy, radiotherapy, biotherapy, immunotherapy, and cell therapy) within 4 weeks or 5 half-lives (whichever is shorter) before the first dose;
• Receipt of major surgery without complete recovery within 4 weeks before the first dose, or planning to undergo major surgery during the study;
• Receipt of systemic immunosuppressants or systemic corticosteroids within 1 week before the first dose;
• Receipt of live-attenuated vaccines within 4 weeks before the first dose, or planning to receive such vaccines during the study;
• Planning to receive any other systemic antitumor therapy (chemotherapy, radiotherapy, biotherapy, immunotherapy, cell therapy, etc.) during the study;
• Symptomatic ascites, pleural effusion or pericardial effusion requiring drainage at screening, or history of drainage for serous effusion within 4 weeks before the first dose;
• History of clinically significant cardiovascular disorders at screening, including but not limited to congestive heart failure (NYHA Class ≥ II), unstable angina, myocardial infarction, stroke or transient ischemic attack (TIA), severe arrhythmias (including but not limited to atrial fibrillation or paroxysmal supraventricular tachycardia, complete left bundle branch block or third-degree atrioventricular block with clinical significance and requiring clinical intervention), or poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) within 6 months before enrollment;
• QT interval corrected by Fridericia's formula (QTcF) ≥470 ms;

Sponsors & Collaborators

• Ruijin Hospital: lead
• Shanghai Essight Bio Co.,Ltd: collaborator

Study Sites (1)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Baiyong Shen

  Ruijin Hospital

  STUDY DIRECTOR

Central Study Contacts

Chenlei Wen

CONTACT

+86-13761638756; wcl12161@rjh.com.cn

Baiyong Shen

CONTACT

+86-(021)-64370045-678801; shenby@shsmu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief physician

Model Details: 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.

Study Record Dates

• First Submitted: June 5, 2026
• First Posted: June 16, 2026
• Study Start: May 18, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)