Clinical Trial of TB511 in Advanced Solid Tumors

Inclusion Criteria:

\[Common\]

1. Male and female adults who are 19 years old or older at the time of obtaining informed consent form.
2. Patients with at least one measurable lesion by RECIST v1.1.
3. Patients whose Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or 1.
4. Female patients of childbearing potential who have not undergone sterilization surgery must agree to use appropriate contraception\* for 6 months after the end of administration of the investigational product and must satisfy one of the following conditions at the time of screening to establish that they are not pregnant.

   • Women over the age of 50 who have had amenorrhea for at least 12 months after the termination of all exogenous hormone treatment.
   * Documented irreversible surgical sterilization by hysterectomy, dual ovariectomy, or oophorectomy (tubal litigation does not satisfy this criteria)
   * Women under the age of 50 who have had amenorrhea for at least 12 months after the termination of all exogenous hormone treatment and whose luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the post-menopause range determined by the clinical trial institution.
5. Male patients who have not undergone vasectomy must agree to use a barrier method of contraception (i.e., condom) and agree that both they and their partners will use an appropriate method of contraception\* through 6 months after the end of administration of the investigational product.

   \*Appropriate methods of contraception include: complete abstinence, hormonal contraceptives not known to have drug interactions \[levonorgestrel-releasing intrauterine system (IUS) (e.g., Mirena), medroxyprogesterone (e.g., Provera)\], copper intrauterine device, and partner's vasectomy. Periodic abstinence (e.g., calendar-based, ovulation tracking, or basal body temperature methods) and withdrawal are not considered appropriate methods of contraception.
6. Patients who have been provided with sufficient explanations on this clinical trial, have voluntarily decided to participate in this clinical trial and have agreed in writing to faithfully comply with the requirements of the clinical trial.

\[Cohort of TB511 Monotherapy in Phase 1 and Phase 2a Clinical Trials\]

1\) Patients with cytologically or histologically confirmed advanced solid tumors who are either refractory or intolerant to standard of care (SoC).

\[Cohort of ICIs Combination Therapy in Phase 2a Clinical Trial\] 1) Patients with advanced solid tumors who, at the time of screening, are refractory to or have experienced disease progression during treatment with immune checkpoint inhibitors (ICIs) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents within their approved indications, and for whom no standard therapy is available.

\- This includes: melanoma, non-small cell lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, gastric cancer, esophageal cancer, renal cell carcinoma, endometrial cancer, microsatellite instability-high (MSI-H) cancer, MSI-H colorectal cancer, triple-negative breast cancer, cervical cancer, biliary tract cancer, and hepatocellular carcinoma.

Exclusion Criteria:

\[Common\] Current Disease and Medical History

1. Patients who have had other malignant tumors within 5 years prior to the screening (provided, however, that patients with basal cell carcinoma that requires only stable long-term follow-up without treatment can be enrolled).
2. Patients who had been subject to chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to the screening.
3. Patients who had undergone major surgery requiring general anesthesia within 4 weeks prior to the screening.
4. Patients with brain metastasis who have symptoms or required treatment (provided, however, that patients with asymptomatic metastasis that does not require treatment \[excluding anticonvulsants used in maintenance therapy\] can be enrolled).
5. Patients with systemic disease for which administration of anti-cancer drugs is deemed inappropriate by the investigator.
6. Patients with the following cardiovascular disease at the screening

   * Myocardial infarction, unstable angina, stroke, or transient ischemic within 6 months.
   * QTc interval ≥ 480 msec or clinically significant electrocardiographic change.
   * Congestive heart failure classified as New York Heart Association (NYHA) class III or above.
7. Patients who are HIV-positive.
8. Patients whose participation in the clinical trial is deemed inappropriate by the investigator based on their results of Hepatitis B virus and Hepatitis C virus test.(Not applicable to patients with hepatocellular carcinoma.)

   However, the following cases are allowed:
   * For patients positive for HBsAg or HBcAb: HBV DNA must be ≤ 2000 IU/mL or undetectable.
   * For patients positive for HCV Ab: HCV RNA must be negative or the patient must have completed antiviral treatment and be stabilized.
9. Patients with acute or severe hepatitis.
10. Patients with autoimmune disease or with history of chronic or recurrent autoimmune disease.
11. Patients with history of organ transplantation.
12. Patients with history of identical hematopoietic stem cell transplantation.
13. Patients with history of interstitial pneumonia requiring steroid treatment.
14. Patients with known hypersensitivity to recombinant drugs (drugs with active ingredients of peptide or protein).
15. Patients with history of hypersensitivity to the components of TB511.

    Prohibited Drugs
16. Patients who require continuous treatment with immunosuppressants or systemic corticosteroid administration (Note: Use of topical corticosteroids such as intra-articular, intranasal, ophthalmic, or inhaled formulations is permitted. Temporary use of systemic corticosteroids administration for the treatment or prevention of contrast agent allergies or adverse reactions is also allowed.)
17. Patients who have received live or attenuated live vaccines within 4 weeks prior to the screening.

    Laboratory tests
18. Patients with the following laboratory levels at the time of screening.

    * ANC \< 1,500/mm³
    * Platelet count \< 100,000/mm³ (for hepatocellular carcinoma: \< 75,000/mm³)
    * Hemoglobin \< 9.0 g/dL (Patients can be enrolled if hemoglobin level is recovered to ≥ 9.0 g/dL during the screening period; however, blood transfusion within 7 days prior to the screening to fulfill this criterion is not allowed.)
    * AST, ALT \> 3 × ULN (provided, however, that if liver metastasis is involved, AST, ALT \> 5 × ULN)
    * Total bilirubin \> 1.5 × ULN
    * Serum creatinine \> 1.5 × ULN

    Others
19. Pregnant, breastfeeding women, or patients with a positive pregnancy test at the time of screening.
20. Patients who, in the investigator's judgment, have an expected survival of less than 12 weeks.
21. Patients who have received other investigational drugs within 4 weeks prior to screening (Patients who did not receive investigational products or who participated only in non-interventional observational studies can be eligible).
22. Any patient deemed unsuitable for participation in this clinical trial at the discretion of the investigator.

\[Only applicable to the cohort of TB511 and ICIs combination therapy in Phase 2a Clinical Trial\]

1. Patients with thyroid-stimulating hormone (TSH) levels above the institutional upper limit of normal (ULN) at the time of screening (Note: patients with abnormal TSH levels may be eligible if free T4 and total T3 levels are within normal ranges).
2. Patients with a history of hypersensitivity to any component of pembrolizumab.