1. Number of participants
\[Phase 1 Clinical Trial\] 3 to 6 patients per dose group
\[Phase 2a Clinical Trial\] Approximately 20 patients per cohort (Cohort 1: Approximately 20 patients, Cohort 2: Approximately 20 patients)
2. Study Duration
* Total clinical trial duration: Approximately 36 months from the date of IRB approval (however, this may be adjusted depending on the enrollment rate of participants.)
* Participation duration for individual participants
* Screening period: Up to 4 weeks (28 days)
* Treatment period: Each cycle consists of 3 weeks (21 days), and administration will continue until a reason for discontinuation occurs.
* 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 ③ Main ingredient: TB511 ④ 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 solution contained in a colorless and transparent vial.
* Main ingredient: Pembrolizumab ④ Storage method: Store in a hermetic container, refrigerated at 2 to 8℃; protect from light; do not freeze
4\. Dosage and method of administration
\[Phase 1 Clinical Trial\]
1. TB511
* Starting Dose group: 4 mg
* Dose Escalation groups: 4 mg, 8 mg, 16 mg, 24 mg
③ Dose De-escalation: 12 mg, 20 mg
④ Administration method: 1 cycle consists of 3 weeks (21 days). TB511 will be administered subcutaneously into the abdomen once every 7 days for 3 weeks (21 days). Repetitive injections at the same site should be avoided; instead, rotate injection sites within the abdominal area. Do not inject into sensitive or abnormal skin areas (e.g., wounds, rashes, redness, induration, etc.).
⑤ Administration Plan: Administration will continue until unacceptable toxicity, disease progression (PD) per RECIST v1.1, or other reasons requiring discontinuation occur.
\[Phase 2a Clinical Trial\]
1. TB511
* Dose: Recommended dose for Phase 2a determined in Phase 1.
② Administration method: 1 cycle consists of 3 weeks (21 days). TB511 will be administered subcutaneously into the abdomen once every 7 days for 3 weeks (21 days). Repetitive injections at the same site should be avoided; instead, rotate injection sites within the abdominal area. Do not inject into sensitive or abnormal skin areas (e.g., wounds, rashes, redness, induration, etc.).
③ Administration Plan: Administration will continue until unacceptable toxicity, disease progression (PD) per RECIST v1.1, or other reasons requiring discontinuation occur.
2. Pembrolizumab
* Dose: 200 mg or dose adjusted according to the approved labeling.
② Administration Method: Pembrolizumab is administered by continuous intravenous infusion for 30 minutes, once every 3 weeks (When used in combination with TB511, Pembrolizumab should be administered first, followed by TB511 at least 30 minutes later).
* Administration Plan: Administration will continue until unacceptable toxicity, disease progression (PD) per RECIST v1.1, or other reasons requiring discontinuation occur.
5\. Study Method
This clinical trial consists of a Phase 1 dose-escalation study to determine the maximum tolerated dose (MTD) of TB511 and establish the recommended Phase 2a dose (RP2D) in patients with advanced solid tumors who are refractory or intolerant to standard of care, and a Phase 2a study to evaluate the anti-tumor effect of TB511 monotherapy in dose determined in Phase 1 (Cohort 1) and TB511 in combination with Pembrolizumab (Cohort 2) in patients with advanced solid tumors for whom no standard of care is available, including those who are refractory to immune checkpoint inhibitors (ICIs) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents or who have experienced disease progression.
Participants who voluntarily sign the written informed consent form will undergo screening tests to assess eligibility during the screening period. Subjects who meet all inclusion and none of the exclusion criteria will be enrolled in this clinical trial and receive the investigational product at the assigned dose level. 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) as defined by RECIST v1.1, or any other reason for discontinuing administration occur. Tumor response assessments (CT/MRI) will be conducted on Day 1 of Cycle 1 and every 2 cycles thereafter. Pharmacokinetic (PK) evaluation will be performed on Day 1 and Day 15 of Cycle 1, and exploratory evaluation will be performed during screening, and on Day 8 and Day 15 of Cycle 1.
\[Phase 1 Clinical Trial - TB511 Monotherapy\] The Phase I clinical trial will follow a 3+3 design, starting from the lowest dose cohort and continuing until the maximum tolerated dose (MTD) is determined. Depending on the MTD determination method, 3 to 6 participants will be sequentially enrolled in each dose-escalation level (TB511: 4 mg, 8 mg, 16 mg, 24 mg) with at least a 3-day interval and TB511 is administered for 1 cycle to determine dose limiting toxicity(DLT). DLT assessment will be conducted in Cycle 1. Dose escalation or de-escalation will be decided by the Safety Review Committee (SRC) after the completion of DLT evaluation of the last participant in each dose level. If no DLT is observed, the study will proceed to the next higher dose level. If DLT occurs, the trial may proceed with an intermediate dose level, as defined below. After completion of dose escalation or de-escalation, the Recommended Phase 2a Dose (RP2D) will be determined based on the MTD and overall toxicity evaluation. The SRC will also decide whether to continue or discontinue the trial.
\<Dose De-escalation Scheme\>
If DLT is observed at a given dose level, the dose will be de-escalated to an intermediate dose\* as follows:
\- If toxicity occurs at 24 mg, the intermediate dose will be 20 mg.
* If toxicity occurs at 16 mg, the intermediate dose will be 12 mg.
* Intermediate dose: An intermediate dose between the given dose level and one-step lower dose level.
