Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of IPM514 in Patients with Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply withthe requirements of the study and the schedule of assessments.

2. Male or female, aged ≥ 18 years.

3. Histologically confirmed diagnosis of esophageal squamous cell carcinoma.

4. Dose escalation and dose expansion stages: After at least one line of systemictreatment (PD-1 antibody combined with platinum-based chemotherapy) has progressedor is intolerable. The following situations are regarded as the failure of thefirst-line standard treatment:

• Tumor recurrence/progression during neoadjuvant/adjuvant immunotherapy combinedwith platinum-containing chemotherapy.

• Patients with disease recurrence within 6 months after completingneoadjuvant/adjuvant treatment, and this neoadjuvant/adjuvant treatment is alsodefined as first-line treatment.

5. Dose escalation and dose expansion stages :At least one measurable lesion by RECISTv1.1, that is, the long diameter of non-lymph node lesions shown by CT or MRI is ≥10mm or the short diameter of lymph node lesions is ≥15 mm. If the CT scan slicethickness is >5 mm, the minimum diameter of the lesion is twice the slice thickness (acceptable examination results within 28 days before signing the ICF).

6. Neoadjuvant treatment cohort: Have not received any anti-tumor treatment foresophageal cancer, including radiotherapy, chemotherapy, surgery, etc.; and plan toreceive surgical treatment after the completion of neoadjuvant treatment.

7. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 or 1.

8. The expected survival period is ≥12 weeks.

9. The HLA typing is HLAA: 0201 and/or HLAA: 1101.

10. The organ function level in the screening period must meet the followingrequirements (no blood transfusion or blood products, no use of hematopoieticstimulating factors and other drugs to correct the number of blood cells before theexamination):

• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;

• Platelet count (PLT) ≥ 100 × 109/L;

• Hemoglobin (Hb) ≥ 90 g/L;

• Total bilirubin (TBIL) ≤ 1.5 × ULN;

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ×ULN, ≤ 5 × ULN for those with liver metastasis;

• Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate (Cockcroft-Gault formula) ≥ 45 mL/min;

• International normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN;

• QTc interval calculated according to the Fridericia standard, ≤ 450 ms for menand ≤ 470 ms for women;

• Urine routine/24-hour urine protein quantification: Urine protein qualitative ≤ 1+ (if urine protein qualitative ≥ 2+, then 24-hour urine protein < 1 g can beenrolled);

• Cardiac function: Left ventricular ejection fraction ≥ 50%.

11. Eligible patients (male or female) with fertility must agree to adopt a medicallyapproved physical contraceptive measure (such as an intrauterine device, condom,tubal or vas deferens ligation, etc.) during the trial and within 6 months after thelast administration; Serum or urine HCG tests of women of childbearing age must benegative in the screening period.

Exclusion Criteria:

1. After stent implantation in esophagus; Patients who are at high risk of bleeding orperforation due to significant tumor invasion of adjacent organs (aorta or trachea).

2. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequentdrainage.

3. Known allergy to the components of the study drug.

4. Prior treatment with an mRNA vaccine.

5. Subjects received major surgery within 4 weeks before the first administration orare expected to receive major surgery during the study (as judged by theinvestigator).

6. Dose escalation and dose expansion stages: Subjects received any anti-tumor therapy,such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, and biologicaltherapy, or any investigational therapy within 28 days or 5 half-lives (whichever isshorter but at least 14 days) of the first study drug administration:

7. Expected to use immunosuppressant drugs during the 4-week period before the firstadministration and during the study, except for corticosteroid nasal sprays,inhalants or systemic prednisone ≤ 10 mg/day and equivalent drugs of the same kind.

8. With a history of organ transplantation, bone marrow transplantation orhematopoietic stem cell transplantation.

9. Received live attenuated vaccines within 28 days before the first administration.

10. Dose escalation and dose expansion stages: Subjects with symptomatic, untreated orrequiring continuous treatment (including corticosteroids and antiepileptic drugs)of central nervous system (CNS) metastasis (for those who have received treatment inthe past, those who have been clinically stable for at least 4 weeks beforeenrollment, have excluded evidence of new or expanded metastasis and havediscontinued steroid treatment can be enrolled; those with asymptomatic brainmetastasis and do not require treatment can be enrolled.

11. 10 Dose escalation and dose expansion stages: The toxicity after previous anti-tumortreatment has not returned to the baseline or grade 0-1 as stipulated in NCI-CTCAEv5.0 (except for hair loss and pigmentation). Those with irreversible toxicitiesthat are not expected to be aggravated by the investigational drug and can beenrolled after confirmation with the investigator.

12. With a history of autoimmune diseases, such as systemic lupus erythematosus,psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory boweldiseases, etc. Type 1 diabetes mellitus, hypothyroidism that can only be controlledby replacement therapy, and skin diseases (such as vitiligo, psoriasis) that do notrequire systemic treatment can be enrolled.

13. With a history of immediate allergic reaction, eczema that cannot be controlled bytopical corticosteroids or asthma.

14. With concomitant diseases that cannot be controlled, including but not limited to:unexplained fever > 38.5°C (subjects with tumor fever are judged by the investigatorwhether to include in the study), symptomatic congestive heart failure with New YorkHeart Association (NYHA) cardiac function classification ≥ grade 2, left ventricularejection fraction (LVEF) < 50%, poorly controlled hypertension (systolic bloodpressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg after treatment, andthe investigator assesses that it is of clinical significance), unstable anginapectoris or acute myocardial infarction occurred within 3 months before the firstadministration, poorly controlled arrhythmia; patients with chronic obstructivepulmonary disease, asthma, interstitial lung disease and those with decreasedpulmonary function.

15. With active infection and currently require systemic anti-infective treatment; thosewith active tuberculosis.

16. Known history of HIV, active Treponema pallidum infection; HBsAg positive andHBV-DNA > 500 IU/L; HCV-RNA positive.

17. Other situations judged by the investigator not suitable for participating in thisstudy, including but not limited to having any diseases or histories that mayconfuse the study results or interfere with the patient's compliance.