Clinical Trial of TB511 in Advanced Solid Tumors

NCT06400160 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: TB001 Version 2.1_2024-10-25
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

• To evaluate the safety and tolerability of TB511 monotherapy in patients with advanced solid tumors and to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D). \[Phase 2a Clinical Trial\]
• To evaluate the Objective Response Rate (ORR) of TB511 monotherapy and TB511 in combination with Pembrolizumab in patients with advanced solid tumors (based on Response Evaluation Criteria In Solid Tumors Version 1.1, RECIST v1.1). 2.2 Secondary Objectives \[Phase 1 Clinical Trial\]
• To evaluate the safety of TB511 monotherapy.
• To assess the Objective Response Rate (ORR) and anti-tumor activity of TB511 monotherapy (based on RECIST v1.1).
• To characterize the pharmacokinetic (PK) profile of TB511 monotherapy. \[Phase 2a Clinical Trial\]
• To evaluate the Disease Control Rate (DCR), Duration of Response (DoR), and Progression-Free Survival (PFS) of TB511 monotherapy and TB511 in combination with Pembrolizumab.
• To assess the safety and tolerability of TB511 monotherapy and TB511 in combination with Pembrolizumab.
• To characterize the pharmacokinetic (PK) profile of TB511 monotherapy and TB511 in combination with Pembrolizumab. 2.3 Exploratory Objectives
• To compare changes in biomarker levels of TB511 monotherapy.
• To assess immunogenicity of TB511 by measuring anti-drug antibodies (ADA).

Conditions

NSCLC; Prostate Cancer; Colorectal Cancer; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Phase I Clinical trial-Maximum tolerated dose (MTD).

  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. 2. 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

• 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

• 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 Outcomes (46)

• Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-the Objective response rate (ORR)

  1 year

• Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Disease control rate (DCR)

  1 year

• Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Duration of response (DoR)

  1 year

• Phase I clinical trial-safety-adverse events of TB511 Monotherapy

  1 year

• Phase I clinical trial-safety-vital signs of TB511 Monotherapy

  1 year

Other Outcomes (6)

• 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

  1 year

• 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

  1 year

• 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

  1 year

Study Arms (2)

TB511

EXPERIMENTAL

* 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

Drug: TB511

Concomitant drug

OTHER

* Product name or code: Keytruda ② Formulation and appearance: An injection comprised of clear to slightly opalescent, colorless to slightly yellow liquid contained in a colorless and transparent vial. ③ Main ingredient: Pembrolizumab * Storage method: Store in a hermetic container, refrigerated at 2 to 8℃; protect from light; do not freeze

Drug: Keytruda

Interventions

TB511 DRUG

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.

TB511

Keytruda DRUG

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.

Concomitant drug

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \[Common\]
• Male and female adults who are 19 years old or older at the time of obtaining informed consent form.
• Patients with at least one measurable lesion by RECIST v1.1.
• Patients whose Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or 1.
• 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.
• 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.
• 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.
• \[Cohort of TB511 Monotherapy in Phase 1 and Phase 2a Clinical Trials\]
• \) 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.

You may not qualify if:

• \[Common\] Current Disease and Medical History
• 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).
• Patients who had been subject to chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to the screening.
• Patients who had undergone major surgery requiring general anesthesia within 4 weeks prior to the screening.
• 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).
• Patients with systemic disease for which administration of anti-cancer drugs is deemed inappropriate by the investigator.
• 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.
• Patients who are HIV-positive.
• 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.

Sponsors & Collaborators

• Twinpig Biolab, Inc.: lead

MeSH Terms

Conditions

Prostatic Neoplasms; Colorectal Neoplasms; Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An Open-label, Multi-center, and Dose-escalation, Phase I/IIa Clinical Trial to Assess the Maximum Tolerated Dose (MTD), Safety, and the Anti-tumor Effect of TB511 Monotherapy in Patients with Advanced Solid Tumors Refractory or Intolerant to Standard of Care (SoC) and Pembrolizumab Combination Therapy in Patients with Advanced Solid Tumors Relapsed or Refractory

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: May 6, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share