Clinical Trial of TB511 in Advanced Solid Tumors

Prostate Cancer Clinical Trial

Official title:

Phase I/IIa Clinical Trial to Assess the Maximum Tolerated Dose (MTD), Safety, and the Anti-tumor Effect of TB511 Monotherapy and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06400160
• Other study ID #: TB001 Version 2.0_2023-12-12
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2024
• Est. completion date: October 2025

Study information

• Verified date: May 2024
• Source: Twinpig Biolab, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. Study population [TB511 Monotherapy Cohort for Phase I and Phase IIa Clinical Trial] Participants with an advanced solid tumor who are either refractory or intolerant to standard of care (SoC).

[Immune checkpoint inhibitors (ICIs) Combination Therapy Cohort for Phase IIa Clinical Trial] Participants with advanced solid tumor who have either not responded to or have relapsed after ICIs that are anti-PD-1 or PD-L1 inhibitors and who have no standard of care available.

2. Objectives of the Clinical Trial [Phase I Clinical Trial] 1) Primary Objective

• To evaluate the safety and tolerability of TB511 monotherapy in Participants with advanced solid tumor to determine maximum tolerated dose (MTD) and recommended Phase IIa dose (RP2D).

2) Secondary Objectives

• To evaluate the safety of TB511 monotherapy.

• To evaluate the objective response rate (ORR) and anti-tumor effect (based on Response Evaluation Criteria in Solid Tumors Version 1.1, RECIST v1.1) of TB511 monotherapy.

• To evaluate the pharmacokinetic characteristics of TB511 monotherapy. 3) Exploratory Objectives

• To compare the changes in biomarker levels of TB511 monotherapy.

• To evaluate immunogenicity by measuring anti-drug antibodies against TB511 [Phase IIa Clinical Trial]

1) Primary Objective

• To evaluate the ORR of TB511 monotherapy and combination therapy with Pembrolizumab in Participants with advanced solid tumors (based on RECIST v1.1).

2) Secondary Objectives

• To evaluate the disease control rate (DCR), duration of response (DoR), and progression-free survival (PFS) of TB511 monotherapy and combination therapy with Pembrolizumab.

• To evaluate the safety and tolerability of TB511 monotherapy and combination therapy with Pembrolizumab.

• To evaluate the pharmacokinetic characteristics of TB511 monotherapy and combination therapy with Pembrolizumab.

3) Exploratory Objectives

• To compare the changes in biomarker levels of TB511 monotherapy.

• To evaluate immunogenicity by measuring anti-drug antibodies against TB511

Description:

1. Number of participants

Phase I Clinical Trial: 3 to 6 participants per dose group Phase IIa Clinical Trial:

Approximately 20 participants per cohort (Cohort 1: Approximately 20 participants, Cohort 2: Approximately 20 participants)

2. Study Duration

Total clinical trial duration: Approximately 36 months from the IRB approval date (however, this may change depending on the time taken by participants to enroll.) Duration of participation of individual participants Screening period: Up to 4 weeks (28 days) Treatment period: 1 cycle consists of 3 weeks (21 days), and administration is continued until there are reasons to suspend administration.

Safety follow-up period: 6 weeks after the end of treatment (EOT)

3. Investigational Product

1. Study drug Product name or code: TB511 Injection (8 mg) Formulation and appearance:

White or off-white color of lyophilized powder Main ingredient: TB511 Storage method:

Store in a hermetic container in a freezer (-20℃); protect from light

2. Concomitant drug Product name or code: Keytruda Formulation and appearance: An injection comprised of clear to slightly opalescent, colorless to slightly yellow liquid contained in a colorless and transparent vial.

Main ingredient: Pembrolizumab Storage method: Store in a hermetic container, refrigerated at 2 to 8℃; protect from light; do not freeze

4. Dosage and method of administration

[Phase I Clinical Trial]

1. TB511 Initial dose: 4 mg Dose escalation: 4 mg, 8 mg, 16 mg, 24 mg Administration method: 1 cycle consists of 3 weeks (21 days). Administer subcutaneously into the abdomen once every 7 days for 3 weeks (21 days). Avoid repeat injection at the same site during subcutaneous injection, and administer injections while changing the location within the same area (abdomen). In addition, do not inject into the skin that is irritated or abnormal (scar, rash, redness, tenderness, etc.).

Administration plan: Administration is continued until intolerable toxicity, verification of progressive disease (PD) under RECIST v1.1 or other reasons for discontinuing administration occur.

[Phase 2a Clinical Trial]

1. TB511 Dose: Recommended dose for Phase IIa determined in Phase I Administration method:

1 cycle consists of 3 weeks (21 days). Administer subcutaneously into the abdomen once every 7 days for 3 weeks (21 days). Avoid repeat injection at the same site during subcutaneous injection, and administer injections while changing the location within the same area (abdomen). In addition, do not inject into the skin that is irritated or abnormal (scar, rash, redness, tenderness, etc.).

Administration plan: Administration is continued until intolerable toxicity, verification of progressive disease (PD) under RECIST v1.1 or other reasons for discontinuing administration occur.

2. Pembrolizumab Dose: 200 mg or dose adjusted in accordance with the label Administration method: Pembrolizumab is administered by continuous intravenous infusion for 30 minutes, once every 3 weeks (if pembrolizumab is administered with TB511, TB511 is administered at least 30 minutes after Pembrolizumab injection).

Administration plan: Administration is continued until intolerable toxicity, verification of progressive disease (PD) under RECIST v1.1 or other reasons for discontinuing administration occur.

5. Study Method

This clinical trial comprises a Phase I dose-escalation study to determine the maximum tolerated dose (MTD) of TB511 in participants with an advanced solid tumor who are either refractory or intolerant to standard of care and to determine the recommended Phase 2a dose (RP2D) and a Phase IIa study to verify the anti-tumor effect of TB511 monotherapy in dose determined in Phase I (Cohort 1) and in combination with Pembrolizumab (Cohort 2) in participants with an advanced solid tumor with no standard of care who have refractory or have relapsed after treatment with anti-PD-1 or PD-L1 ICIs.

Participants who have voluntarily signed the written informed consent form undergo a screening test to verify eligibility of participation in this clinical trial during the screening period. Participants who have been determined to be eligible in accordance with the inclusion and exclusion criteria are enrolled into this clinical trial and receive the determined dose of the investigational product. 1 cycle of administration of the investigational product is 3 weeks (21 days), and enrolled participants continue to receive the investigational product until intolerable toxicity, verification of progressive disease (PD) under RECIST v1.1 or other reasons for discontinuing administration occur. RECIST (CT/MRI) is performed on Day 1 of cycle 1 and every 2 cycles thereafter. Pharmacokinetic evaluation is performed on Day 1 and Day 21 of Cycle 1, and exploratory evaluation is conducted at the screening and Day 21 of Cycle 1.

[Phase I Clinical Trial] TB511 Monotherapy Phase I clinical trial is conducted on a 3 + 3 basis beginning with the lowest-dose cohort until MTD is determined. Depending on the method of determining MTD, 3 to 6 participants are enrolled in the order for each dose level (TB511: 4 mg, 8 mg, 16 mg, 24 mg) with a minimum interval of 3 days, and TB511 is administered for Cycle 1 in order to determine DLT. DLT assessment is conducted in Cycle 1, and whether to escalate dose is determined by the Safety Review Committee (SRC) after the Cycle 1 DLT assessment has been completed for the last participant. RP2D of Phase IIa clinical trial is determined through MTD and overall toxicity assessment.

[Phase IIa Clinical Trial] Phase IIa clinical trial is conducted in approximately 20 participants with an advanced solid tumor for which there is no standard of care, who is subject to TB511 monotherapy cohort (Cohort 1) and approximately 20 participants with advanced solid tumor who have refractory or have relapsed after treatment with anti-PD-1 or ICIs that are PD-L1 inhibitors and for whom there is no standard of care, who is subject to TB511 and Pembrolizumab combination therapy cohort (Cohort 2).

Cohort 1 (TB511 Monotherapy Cohort) For Cohort 1, participants are enrolled consecutively and treated with the RP2D dose of TB511 determined in the Phase I clinical trial.

Cohort 2 (TB511 and Pembrolizumab Combination Cohort) For Cohort 2, the first 3 participants are enrolled serially with a minimum interval of 3 days and administered in combination of the RP2D dose of TB511 and Pembrolizumab for Cycle 1 to evaluate DLT. If DLT occurs, the 3 + 3 design is applied, and the SRC, thereby evaluate the safety of a total of 6 participants. When DLT occurs in 2 out of 3 to 6 subjects, the safety of combination therapy of a TB511 dose lower than the RP2D determined in Phase I and Pembrolizumab may be evaluated by the SRC in the same manner as above. If the safety of combination therapy of TB511 and Pembrolizumab is determined per the decision of the SRC, the remaining participants are simultaneously enrolled and participate in the clinical trial.

[Phase IIa Study Scheme]

1) Definition and Assessment of Dose Limiting Toxicity (DLT) DLT is an adverse event or abnormal laboratory level unrelated to the progress of the disease or intercurrent disease that limits dose escalation and is consistent with one or more of the following criteria: DLT assessment is conducted only at Cycle 1 after completion of Cycle 1. However, even during Cycle 1, DLT can be immediately evaluated if toxicity is determined to be DLT. DLT assessment is conducted in accordance with NCI-CTCAE v5.0 based on individual assessment items on hematological/non-hematological toxicity and other toxicities.

6. Endpoints

1. Safety Endpoints Adverse Events Vital signs Physical examination Electrocardiogram Laboratory test

2. Primary endpoint (Response Evaluation Criteria in Solid Tumors - RECIST) [Phase I Clinical Trial] Solid tumor response is evaluated in accordance with RECIST v1.1. Objective response rate (ORR): Fraction of participants whose best overall response is Complete Response (CR) or Partial Response (PR) Disease control rate (DCR): Fraction of participants whose best overall response is CR, PR or Stable Disease (SD) Duration of response (DoR): From the point of time when response occurs to (CR or PR) PD or death due to any reason.

[Phase IIa Clinical Trial] Solid tumor response is evaluated in accordance with RECIST v1.1 and immune RECIST (iRECIST).

Objective response rate (ORR): Fraction of participants whose best overall response is CR or PR Disease control rate (DCR): Fraction of participants whose best overall response is CR, PR or SD Duration of response (DoR): From the point of time when response occurs to (CR or PR) PD or death due to any reason.

Progression-free survival (PFS) period: Period from the initial date of administration of the investigational product to the date when objective progressive disease (PD) is verified by the investigator, or the date of death, whichever occurs first.

3. Pharmacokinetic endpoint Blood is collected on Day 1 and Day 21 of Cycle 1 from available participants among the participants of this clinical trial for pharmacokinetic evaluation. In all clinical trials, blood collection for pharmacokinetic evaluation is performed prior to the administration of the investigational product (- 60 minutes), and after the administration of the investigational product, at 0.16 h (± 3 minutes), 0.5 h (± 3 minutes), 1 h (± 5 minutes), 2 h (± 10 minutes), 4 h (± 10 minutes), 8 h (± 30 minutes), and 24 h (± 30 minutes).

Cycle 1, Day 1: AUClast, AUCinf, Cmax, Tmax, t1/2, CL/F, Vd/F Cycle 1, Day 21:

AUClast,ss, AUCtau,ss, AUCinf,ss, Cmax,ss, Tmax,ss, t1/2,ss, CLss/F, Vd,ss/F

4. Exploratory endpoints Compare changes of the biomarker from the value before TB511 treatment (screening visit) to the post-treatment value (Day 21).

Category Analysis method Examination items Tumor tissue ELISA CD18, CD163, TGF-ß1, IL-10, VEGF, IFN-γ, Granzyme B Blood ELISA TGF-ß1, VEGF, TNF-α, IFN-γ, IL-2 Flow cytometer (Tcell, NK cell) CD45, CD3(CD45+CD3+: T cells), CD4, IFN-γ (Activation), CD25, CD8, Granzyme B(Activation), CD56 (CD45+CD3-CD19-CD56: NK), CD19(CD45+CD3-CD19+: B cell)

Anti-drug antibody (ADA) to TB511 is measured on Day 1 of Cycle 1 and every 2 cycles, both before and after the administration of TB511, end of study, and safety follow-up (if needed), to compare changes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: October 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

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 or evaluable 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 the use of interceptive birth-control methods (i.e., condoms) and must agree that appropriate contraception is used by himself and his partner for 6 months after the end of administration of the investigational product.

*Appropriate means of birth control: Complete abstinence, contraception hormonal agent of unknown drug interactions [levonorgestrel intrauterine system (IUS) (Mirena), medroxyprogesterone (Provera)], copper intrauterine device, and vasectomy by the male partner. Provided, however, that occasional abstinence (for example, abstinence based on ovulation time or symptomatic thermometry) is not considered an appropriate 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.

Exclusion Criteria:

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 = 450 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.

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 systemic corticosteroid administration (provided, however, that local use of corticosteroid, such as in joints, nasal cavity, eyes, or inhalation, and temporary systemic corticosteroid administration to treat and prevent the subject's contrast medium allergy or adverse event is permitted).

17. Patients who had been administered with live vaccine or attenuated live vaccine within 4 weeks prior to the screening.

Laboratory tests

18. Patients whose laboratory levels are as follows as of the screening.

• ANC < 1,500/mm³

• Platelet count < 100,000/mm³

• Hemoglobin < 9.0 g/dL (if hemoglobin level is recovered to over 9.0 g/dL during the screening period, the patient can be enrolled. Provided, however, that blood transfusion conducted 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 who are positive on a pregnancy test at the screening.

20. Patients whose remaining life expectancy is determined to be less than 12 weeks by the investigator.

21. Patients who have been treated with another investigational product within 4 weeks to the screening (patients who have not been treated with the investigational product or participated in a non-interventional study can be enrolled)

22. Patients with a history of drug or alcohol abuse

23. Patients whose participation in the clinical trial is deemed inappropriate by the investigator.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Colorectal Cancer
• Hepatocellular Carcinoma
• NSCLC
• Prostate Cancer

Intervention

Drug:
• TB511
TB511 is a peptide drug conjugate (PDC) which composed of TAMpep826 peptide. TB511 is a white amorphous powder used for subcutaneous injections. TB511 is a peptide drug conjugate that combines a transporter peptide with a specific targeting of M2 macrophages and an apoptosis-inducing peptide (dKLA). As a transporter, the M2 binding peptide acts as a drug conjugate, explicitly binding to M2 macrophages and inducing cell penetration. In the cells, the dKLA component of TB511 binds to the mitochondrial membrane, destroys the mitochondrial membrane, and induces apoptosis by causing cytochrome release, leading to the destruction of the mitochondria and subsequent death of M2 macrophages.
• Keytruda
KEYTRUDA binds to the PD - 1 receptor, blocking both immune-suppressing ligands, PD L1 and PD L2, from interacting with PD - 1 to help restore T-cell response and immune response.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Twinpig Biolab, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phase I clinical trial-Exploratory Objectives-Biomaker evaluation-class • To compare the changes in biomarker levels of TB511 monotherapy. • To evaluate immunogenicity by measuring anti-drug antibodies against TB511	Phase I Clinical Trial: 3 to 6 subjects per dose group : Compare changes of the biomarker from the value before TB511 treatment (screening visit) to the post-treatment value (Day 21).; Tumor tissue-ELISA-CD18, CD163, TGF-ß1, IL-10, VEGF, IFN-?, Granzyme B Blood-ELISA-TGF-ß1, VEGF, TNF-a, IFN-?, IL-2 Flow cytometer (Tcell, NK cell); -CD45, CD3(CD45+CD3+: T cells), CD4, IFN-? (Activation), CD25, CD8, Granzyme B(Activation), CD56 (neededCD45+CD3-CD19-CD56: NK), CD19(CD45+CD3-CD19+: B cell)	1 year
Other	Phase I clinical trial-Exploratory Objectives-Biomaker evaluation-method • To compare the changes in biomarker levels of TB511 monotherapy. • To evaluate immunogenicity by measuring anti-drug antibodies against TB511	From the blood collected, the serum will be separated and aliquoted into a tube and kept in a freezer below - 70°C until delivery to the analysis institution. Each tube will be labeled with a subject enrollment number, sampling date, etc; each label will be affixed with tape before storage in a freezer.; Tumor tissue biomarkers and blood biomarkers will be analyzed using ELISA and a flow cytometer. Tumor tissues will be placed in PBS and crushed using a homogenizer. After centrifuge, the supernatant will be used for ELISA analysis.; Blood samples will be divided into two: whole blood samples for the flow cytometer and plasma samples for ELISA analysis. Blood and tumor tissues will be analyzed by an external analysis institution. For sample handling and analysis methods, refer to the separately provided manual and the analysis protocol and SOPs of the analysis institution.	1 year
Other	Phase I clinical trial-Exploratory Objectives-Anti-drug antibody evaluation • To compare the changes in biomarker levels of TB511 monotherapy. • To evaluate immunogenicity by measuring anti-drug antibodies against TB511	From the blood collected, the serum will be separated and aliquoted into a tube and kept in a freezer below -70°C until delivery to the analysis institution. Each tube will be labeled with a subject enrollment number, sampling date, etc; each label will be affixed with tape before storage in a freezer.; ADA to TB511 will be analyzed using ELISA. For ADA analysis, ADA to TB511 will be obtained and sent to an external analysis institution (Bio Infra) together with TB511 capture antibody for analysis. For sample handling and analysis methods for ADA analysis, refer to the separately provided manual and the analysis protocol and SOPs of the analysis institution.	1 year
Other	Phase IIa clinical trial-Exploratory Objectives-Biomaker evaluation-class	Biomarker evaluation Phase IIa Clinical Trial: Approximately 20 subjects per cohort (Cohort 1: Approximately 20 subjects, Cohort 2: Approximately 20 subjects) : Compare changes of the biomarker from the value before TB511 treatment (screening visit) to the post-treatment value (Day 21).; Tumor tissue-ELISA-CD18, CD163, TGF-ß1, IL-10, VEGF, IFN-?, Granzyme B Blood-ELISA-TGF-ß1, VEGF, TNF-a, IFN-?, IL-2 Flow cytometer (Tcell, NK cell); -CD45, CD3(CD45+CD3+: T cells), CD4, IFN-? (Activation), CD25, CD8, Granzyme B(Activation), CD56 (CD45+CD3-CD19-CD56: NK), CD19(CD45+CD3-CD19+: B cell)	2 years
Other	Phase IIa clinical trial-Exploratory Objectives-Biomaker evaluation-method	From the blood collected, the serum will be separated and aliquoted into a tube and kept in a freezer below - 70°C until delivery to the analysis institution. Each tube will be labeled with a subject enrollment number, sampling date, etc; each label will be affixed with tape before storage in a freezer.; Tumor tissue biomarkers and blood biomarkers will be analyzed using ELISA and a flow cytometer. Tumor tissues will be placed in PBS and crushed using a homogenizer. After centrifuge, the supernatant will be used for ELISA analysis.; Blood samples will be divided into two: whole blood samples for the flow cytometer and plasma samples for ELISA analysis. Blood and tumor tissues will be analyzed by an external analysis institution. For sample handling and analysis methods, refer to the separately provided manual and the analysis protocol and SOPs of the analysis institution.	2 years
Other	Phase IIa clinical trial-Exploratory Objectives-Anti-drug antibody evaluation	From the blood collected, the serum will be separated and aliquoted into a tube and kept in a freezer below -70°C until delivery to the analysis institution. Each tube will be labeled with a subject enrollment number, sampling date, etc; each label will be affixed with tape before storage in a freezer.; ADA to TB511 will be analyzed using ELISA. For ADA analysis, ADA to TB511 will be obtained and sent to an external analysis institution (Bio Infra) together with TB511 capture antibody for analysis. For sample handling and analysis methods for ADA analysis, refer to the separately provided manual and the analysis protocol and SOPs of the analysis institution.	2 years
Primary	Phase I Clinical trial-Maximum tolerated dose (MTD).	Definition and Assessment of Dose Limiting Toxicity (DLT) DLT is an adverse event or abnormal laboratory level unrelated to the progress of the disease or intercurrent disease that limits dose escalation and is consistent with one or more of the following criteria: DLT assessment is conducted only at Cycle 1 after completion of Cycle 1. However, even during Cycle 1, DLT can be immediately evaluated if toxicity is determined to be DLT. DLT assessment is conducted in accordance with NCI-CTCAE v5.0 based on individual assessment items on hematological/non-hematological toxicity and other toxicities.; Definition and Determination of Maximum Tolerated Dose (MTD) When 2 out of 3 subjects or 2 out of 6 subjects experience DLTs, the dose is considered intolerable, the subsequent dose escalation is stopped, and a level lower than the dose is declared the maximum tolerable dose (MTD).	1 year
Primary	Phase I Clinical trial-Recommended Phase IIa dose (RP2D).	RP2D of Phase IIa clinical trial is determined through MTD and overall toxicity assessment.	1 year
Primary	Phase IIa Clinical trial-anti-tumor effect-to evaluate the Objective response rate (ORR) of TB511 monotherapy and combination therapy with Pembrolizumab in patients with advanced solid tumors (based on RECIST v1.1).	Solid tumor response is evaluated in accordance with RECIST v1.1 and immune RECIST (iRECIST).; Objective response rate (ORR): Fraction of subjects whose best overall response is Complete Response (CR) or Partial Response (PR)	2 years
Secondary	Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-the Objective response rate (ORR)	Solid tumor response is evaluated in accordance with RECIST v1.1. Objective response rate (ORR): Fraction of subjects whose best overall response is Complete Response (CR) or Partial Response (PR)	1 year
Secondary	Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Disease control rate (DCR)	Disease control rate (DCR): Fraction of subjects whose best overall response is CR, PR or Stable Disease (SD)	1 year
Secondary	Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Duration of response (DoR)	Duration of response (DoR): From the point of time when response occurs to (CR or PR) PD or death due to any reason.	1 year
Secondary	Phase I clinical trial-safety-adverse events of TB511 Monotherapy	Safety Assessment and Method of Assessment; 1) Adverse Events Adverse events are a general term for symptoms, signs, and abnormal values of laboratory tests that occur or worsen after the administration of an investigational product. The AE name, onset/end dates, severity, treatment and outcomes, and relationship to the investigational product should be documented in the AE pages of the eCRFs.	1 year
Secondary	Phase I clinical trial-safety-vital signs of TB511 Monotherapy	2) Vital signs Findings of vital signs that meet the definitions of AEs after the administration of the investigational product should be reported as AEs.	1 year
Secondary	Phase I clinical trial-safety-physical examination and ECG of TB511 Monotherapy	3) Physical examination and ECG After the administration of the investigational product, findings in physical examinations that meet the definitions of AEs or ECGs showing clinically significant changes should be reported as AEs.	1 year
Secondary	Phase I clinical trial-safety-laboatory test of TB511 Monotherapy	4) Laboratory test Laboratory test results will be categorized into normal or abnormal (NCS or CS). Any result after the administration of the investigational product showing clinically significant changes from baseline should be reported as AEs.	1 year
Secondary	PK parameters for TB511 (Area Under the Curve from 0 to 24 h (AUC)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 AUC	1 year
Secondary	PK parameters for TB511 (AUC to the Last Measurable Concentration from 0 to 24 h (AUClast)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 AUClast	1 year
Secondary	PK parameters for TB511 (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h (AUCinf)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 AUCinf	1 year
Secondary	PK parameters for TB511 (Peak Plasma Concentration from 0 to 24 h (Cmax)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 Cmax	1 year
Secondary	PK parameters for TB511 (Time to Obtain Maximum Plasma Concentration from 0 to 24 h (Tmax)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 Tmax	1 year
Secondary	PK parameters for TB511 from 0 to 24 h (half-life (t1/2)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 half-life (t1/2)	1 year
Secondary	PK parameters for TB511 (Clearance from 0 to 24 h (CL/F)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 CL/F	1 year
Secondary	PK parameters for TB511 (Volume of distribution from 0 to 24 h (Vd/F)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 Vd/F	1 year
Secondary	PK parameters for TB511 (Area Under the Curve from 0 to 24 h at steady-state (AUCss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 AUCss	1 year
Secondary	PK parameters for TB511 (AUC to the Last Measurable Concentration from 0 to 24 h at steady-state (AUClast ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 AUClast, ss	1 year
Secondary	PK parameters for TB511 (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h at steady-state (AUCinf, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 AUCinf, ss	1 year
Secondary	PK parameters for TB511 (Peak Plasma Concentration from 0 to 24 h at steady-state (Cmax ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 Cmax, ss	1 year
Secondary	PK parameters for TB511 (Time to Obtain Maximum Plasma Concentration from 0 to 24 h at steady-state (Tmax, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 Tmax, ss	1 year
Secondary	PK parameters for TB511 (half-life from 0 to 24 h at steady-state (t1/2, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 half-life (t1/2, ss)	1 year
Secondary	PK parameters for TB511 (Clearance from 0 to 24 h at steady-state (CL, ss/F)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 CL, ss/F	1 year
Secondary	PK parameters for TB511 (Volume of distribution from 0 to 24 h at steady-state (Vd, ss/F)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 Vd, ss/F	1 year
Secondary	Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Disease control rate (DCR)	Disease control rate (DCR): Fraction of subjects whose best overall response is CR, PR or SD	2 years
Secondary	Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Duration of response (DoR)	Duration of response (DoR): From the point of time when response occurs to (CR or PR) PD or death due to any reason.	2 years
Secondary	Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Progression-free survival (PFS) period	Progression-free survival (PFS) period: Period from the initial date of administration of the investigational product to the date when objective progressive disease (PD) is verified by the investigator, or the date of death, whichever occurs first.	2 years
Secondary	Phase IIa-the safety-adverse events of TB511 Monotherapy and TB511 & pembronizumab compination therapy	1) Adverse Events Adverse events are a general term for symptoms, signs, and abnormal values of laboratory tests that occur or worsen after the administration of an investigational product. The AE name, onset/end dates, severity, treatment and outcomes, and relationship to the investigational product should be documented in the AE pages of the eCRFs.	2 years
Secondary	Phase IIa-the safety-vital signs of TB511 Monotherapy and TB511 & pembronizumab compination therapy	2) Vital signs Findings of vital signs that meet the definitions of AEs after the administration of the investigational product should be reported as AEs.	2 years
Secondary	Phase IIa-the safety-Physical examination and ECG of TB511 Monotherapy and TB511 & pembronizumab compination therapy	3) Physical examination and ECG After the administration of the investigational product, findings in physical examinations that meet the definitions of AEs or ECGs showing clinically significant changes should be reported as AEs.; Findings of vital signs that meet the definitions of AEs after the administration of the investigational product should be reported as AEs.	2 years
Secondary	Phase IIa-the safety-Laboratory test of TB511 Monotherapy and TB511 & pembronizumab compination therapy	4) Laboratory test Laboratory test results will be categorized into normal or abnormal (NCS or CS). Any result after the administration of the investigational product showing clinically significant changes from baseline should be reported as AEs.	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Area Under the Curve from 0 to 24 h (AUC)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUC	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (AUC to the Last Measurable Concentration from 0 to 24 h (AUClast)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUClast	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h (AUCinf)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUCinf	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Peak Plasma Concentration from 0 to 24 h (Cmax)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Cmax	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Time to Obtain Maximum Plasma Concentration from 0 to 24 h (Tmax)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Tmax	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (half-life from 0 to 24 h (t1/2)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination half-life (t1/2)	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Clearance from 0 to 24 h (CL/F)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination CL/F	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Volume of distribution from 0 to 24 h (Vd/F)) [Time Frame: Day 1 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Vd/F	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Area Under the Curve from 0 to 24 h at steady-state (AUCss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUCss	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (AUC to the Last Measurable Concentration from 0 to 24 h at steady-state (AUClast ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUClast, ss	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h at steady-state (AUCinf, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination AUCinf, ss	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Peak Plasma Concentration from 0 to 24 h at steady-state (Cmax ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Cmax, ss	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Time to Obtain Maximum Plasma Concentration from 0 to 24 h at steady-state (Tmax, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Tmax, ss	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (half-life from 0 to 24 h at steady-state (t1/2, ss)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination half-life (t1/2, ss)	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Clearance from 0 to 24 h at steady-state (CL, ss/F)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination CL, ss/F	2 years
Secondary	PK parameters for TB511 and Pembrolizumab combination (Volume of distribution from 0 to 24 h at steady-state (Vd, ss/F)) [Time Frame: Day 21 of first 1 cycle]	Determine TB511 and Pembrolizumab combination Vd, ss/F	2 years