A Phase I, First in Human (FIH), Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Preliminary Efficacy and Immunogenicity of TJ101 for Injection in Patients With Advanced/Metastatic Solid Tumors

Study Identifier:
TJ101-I-001
CT.gov Identifier:
NCT07181473
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

Considering participating in a START clinical trial?

Get Started

Study Summary

To evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of TJ101, a bispecific antibody-drug conjugate (ADC) targeting EGFR and B7-H3, in patients with advanced or metastatic solid tumors.

To evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of TJ101 for injection in subjects with advanced solid tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bladder
Non-Small Cell Lung Cancer
Prostate
Small Cell Lung
Head & Neck
Solid Tumor
Digestive & Intestinal
Neuroendocrine
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: TJ101
Read More
Drug: Chinese common name: TJ101 injection
Drug: Dosage form: Lyophilized powder for injection
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
Inclusion criteria
  • 1. Histological and/or cytological diagnosis of advanced/metastatic solid tumors, who have failed standard treatment, or have no standard therapy.
  • 2. Have at least one measurable lesion by RECIST v1.1 (Eisenhauer et al., 2009) for solid tumors.
  • 3. Men or women ≥18 years old.
  • 4. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) of 0 to 1.
  • 5. Life expectancy of ≥ 12 weeks;
  • 6. Patients with adequate organ function and the laboratory test criteria specifically defined as follows within 7 days prior to the first dosing.
  • 1. Hepatic function AST and ALT ≤ 2.5 x upper limit of normal (ULN); if liver metastases, then ≤ 5 x ULN. Total bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome.
  • Albumin ≥3g/dL.
  • 2. Coagulation function:
  • International normalized ratio (INR) ≤ 1.5×ULN; APTT≤1.5×ULN.
  • 3. Renal function Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft and Gault equation) (Cockcroft DW, 1976)
  • 4. Hematopoietic function (without infusion of blood product, use of G-CSF or other treatments to correct blood count within 14 days) Hemoglobin (HGB) ≥ 90 g/L; Platelet count (PLT) ≥ 100×109/L Absolute neutrophil count (ANC) ≥ 1.5×109/L;
  • 7. Serum pregnancy test (for female of childbearing potential) negative within 7 days prior to first dosing of study treatment. Male and female patients of childbearing potential must agree to use effective methods of contraception from the time of informed consent, throughout the study and for 6 months after the last dose of the investigational product.
  • 8. Willing to participate in the clinical trial, understand and sign the informed consent, and comply with the study visits and procedures.
  • CFDA
  • Tumor types that meet the following criteria: Subjects with histologically or cytologically confirmed recurrent or metastatic advanced malignant solid tumors that have failed or are intolerant to standard treatment or have no standard treatment options. Priority is given to non-small cell lung cancer (NSCLC), small cell lung cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, prostate cancer, or bladder cancer.
  • 2 The subject had at least one measurable lesion according to RECIST 1.1.
  • 3 Male or female aged ≥18 years.
  • 4 Eastern Cooperative Oncology Group (ECOG) performance status score (Appendix 1) is 0-1.
  • 5 The expected survival time is ≥12 weeks.
  • 6 Adequate vital organ function and laboratory indicators must be present at screening, as defined below: a) Liver function: ? For subjects without liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); for subjects with liver metastasis, ALT or AST ≤ 5 × ULN; ? Total serum bilirubin (TBIL) ≤ 1.5 × ULN; for subjects with liver metastasis or confirmed Gilbert's syndrome, TBIL ≤ 3 × ULN. b) Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN; c) Renal function: creatinine clearance (CLCr) calculated according to the Cockcroft-Gault method (Appendix 3) ≥ 60 mL/min; d) Bone marrow function (no blood product transfusion, G-CSF, or other treatment to correct blood cell counts within 14 days): ? Hemoglobin (HGB) ≥90 g/L (9 g/dL); Platelet count (PLT) ≥100×109/L; Absolute neutrophil count (ANC) ≥1.5×109/L;
  • 7 Female subjects of childbearing age must have a negative blood pregnancy test within 7 days before the first use of the trial drug. Subjects of childbearing potential (male and female) must agree to use reliable contraception with their partners during the trial and for at least 6 months after the last dose, starting from the signing of the ICF. Women of childbearing age are defined as those who have not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) and are premenopausal (amenorrhea ≤ 12 months).
  • 8 Volunteer to participate in this drug clinical trial, be able to understand and sign the informed consent, and comply with study visits and study-related procedures and assessments.
Exclusion criteria
  • 1. Has received treatment of topoisomerase 1 inhibitors (TOP1i), including topotecan, irinotecan, belotecan, and TOP1i-based antibody-drug conjugates (ADCs, eg, sacituzumab govitecan, trastuzumab deruxtecan, zalontamab brengitecan, sacituzumab tirumotecan etal);
  • 2. Has known hypersensitivity to any component of TJ101 or has a history of severe hypersensitivity reactions to other monoclonal antibodies;
  • 3. Has received mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks prior to the first administration; Has received other chemotherapy, biological therapy, immunotherapy, major surgery, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase) and other anti-tumor therapy within 5 half-lives or 28 days, whichever is shorter, prior to the first administration of TJ101; Has received anti-tumor herbal medicine within 14 days prior to first dose of TJ101;
  • 4. Has received a strong or moderate CYP3A4 inhibitor within 3 half-lives;
  • 5. Received an investigational drug within 28 days or 2 half-lives (whichever is shorter) prior to first dose of TJ101; Current participation in other interventional clinical studies (participation in survival follow-up is allowed);
  • 6. Toxic effects of prior anti-tumor therapy have not recovered to NCI-CTCAE V5.0 Grade ≤1 (excluding alopecia and skin pigmentation). Subject with irreversible toxicities caused by prior anti-tumor therapy (eg, hearing loss) that will not increase the safety risk may be eligible at the discretion of the Investigator.
  • 7. Has a history of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis can't be ruled out by imaging at screening.
  • 8. Presence of severe dry eye syndrome, severe keratitis, severe conjunctivitis, or other severe conditions that may increase the risk of corneal epithelial damage at the discretion of investigator.
  • 9. Uncontrolled or significant cardiovascular disease, including:
  • Prolongation of the average Corrected QT interval (QTc, Fridericia's correction formula used) (> 470 ms regardless of sex).
  • Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (class II-IV of New York Heart Association [NYHA]) or acute myocardial infarction within preceding 6 months.
  • History of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  • Uncontrolled hypertension defined as systolic BP ≥160 mm Hg or diastolic BP ≥100 mm Hg while receiving more than one kind of antihypertensive drug.
  • 10. For patients with documented positive virology status of hepatitis, as confirmed by Screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests, only the following patients may be eligible as evaluated by the sponsor and investigator:
  • Patients with active hepatitis B: HBV DNA ≤500 IU/mL during Screening. Patients who are hepatitis C virus antibody positive (HCV Ab+), who have controlled infection (HCV RNA≤ULN by polymerase chain reaction [PCR] either spontaneously or in response to a successful prior course of anti-HCV therapy at Screening). Patients with controlled infections must undergo periodic monitoring of HCV RNA as per treating physician.
  • 11. Known HIV infection;
  • 12. Severe infection, including but not limited to hospitalization due to infection, bacteraemia, or severe pneumonia complications, occurs within 4 weeks prior to initiation of study treatment; Or patients who received therapeutic oral or intravenous antibiotics within two weeks prior to starting study treatment, and who received prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease);
  • 13. Active central nervous system (CNS) metastases or meningeal metastases. Subjects may be enrolled in the study if their CNS metastases have received adequate local therapy and have been clinical stable for at least 4 weeks (ie, imaging shows no progression of the brain lesion and neurologically relevant symptoms are stable), and require a dose of prednisone of ≤20 mg/day (or equivalent dose).
  • 14. Other malignancies within 3 years prior to initiation of TJ101 treatment (other than non-melanoma basal cell carcinoma or squamous cell carcinoma of the skin, breast/cervical carcinoma in situ, superficial bladder carcinoma that have received radical treatment and no evidence of disease recurrence) will confound safety/efficacy of this trial or pose a risk to the participants;
  • 15. Female patients who are lactating or breastfeeding.
  • 16. The investigator believes that the subject may have other factors that may affect the results of the study and interfere with the subject's participation in the entire study process, including previous or existing physical conditions, abnormal treatment or laboratory tests, and the subject's unwillingness to comply with all procedures, restrictions, and requirements of the study.
  • CFDA
  • Previous treatment with topoisomerase I inhibitors, including chemotherapy drugs such as topotecan, irinotecan, belotecan, or antibody-drug conjugates containing topoisomerase I inhibitors (e.g., gosatuzumab, trastuzumab, BL-B01D1, SKB264, etc.);
  • 2Hypersensitivity to the investigational drug TJ101 and its formulation components, or severe allergy to other monoclonal antibodies;
  • 3Major surgery (craniotomy, thoracotomy, laparotomy, or other major surgery assessed by the investigator), chemotherapy, or radiotherapy within 28 days prior to the first dose of TJ101 for injection; Receipt of anti-tumor Chinese medicine within 14 days prior to the first dose of TJ101; Receipt of other anti-tumor drugs within 28 days or within 5 half-lives (whichever is shorter) prior to the first dose of TJ101;
  • 4Use of strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors within three half-lives prior to the first dose of TJ101 for injection (Appendix 4);
  • 5Received other unapproved clinical research drugs or treatments within 28 days before the first dose, or is participating in other interventional clinical studies (except those in the survival follow-up stage);
  • 6Toxicity caused by previous anti-cancer therapy has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 ≤ Grade 1 (excluding alopecia and hyperpigmentation). Patients with irreversible toxicity caused by previous anti-cancer therapy (such as hearing loss) can be enrolled if the investigator determines that it will not increase the safety risk.
  • 7History of (non-infectious) interstitial lung disease (ILD) requiring steroids and current ILD/pneumonia.
  • 8The presence of severe dry eye syndrome, severe keratitis, severe conjunctivitis, and other conditions that the investigators determined may increase the risk of corneal epithelial damage.
  • 9Uncontrolled or clinically significant cardiovascular disease, including but not limited to: Prolonged corrected QT interval (QTc, using Fridericia's correction formula), QTc > 470 ms in males or females; Unstable angina, acute myocardial infarction, congestive heart failure (New York Heart Association NYHA class II to IV heart disease) within 6 months prior to study treatment; Severe arrhythmias, other risk factors for Torsade de Pointes (TdP) (such as heart failure, hypokalemia, hypomagnesemia, family history of long QT syndrome, etc.); Uncontrolled hypertension, defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg even with multiple antihypertensive drug treatment.
  • 10Active hepatitis B or C. Active hepatitis B is defined as: hepatitis B surface antigen (HBsAg) positive and HBV DNA > 500 IU/ml; active hepatitis C is defined as: hepatitis C antibody positive and HCV RNA above the upper limit of normal value of the study center;
  • 11Known HIV infection;
  • 12Concurrent serious infection, including but not limited to hospitalization for infection, bacteremia or severe pneumonia complications within 4 weeks before the start of study treatment; or receiving therapeutic oral or intravenous antibiotics within 2 weeks before the start of study treatment;
  • 13Active central nervous system (CNS) metastases or meningeal metastases. Subjects with CNS metastases limited to the supratentorial and/or cerebellum (i.e., no midbrain, pons, medulla oblongata, or spinal cord metastases), who have received adequate local treatment and have been clinically stable for at least 4 weeks (imaging shows no progression of brain lesions and stable neurological symptoms), and who do not require glucocorticoid therapy or a prednisone dose ≤ 10 mg/day (or equivalent), may participate in the study.
  • 14Patients with other malignant tumors within 3 years before the start of study treatment (excluding non-melanoma skin basal cell carcinoma or squamous cell carcinoma, breast/cervical carcinoma in situ, superficial bladder cancer and other carcinomas in situ that have been radically treated and have no evidence of disease recurrence);
  • 15Pregnant or breastfeeding women.
  • 16The researcher assesses that the subject has other factors that may affect the study results and interfere with his/her participation in the entire study process, including previous or current physical conditions, treatments or laboratory test abnormalities, and the subject may be unable to comply with the various procedures, restrictions and requirements of the study.

Clinical Study Information for Healthcare Providers

By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

View Study Information

Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Will Be Recruiting
Condition(s) Treated at Site
Bladder
Non-Small Cell Lung Cancer
Prostate
Small Cell Lung
Head & Neck
Solid Tumor
Digestive & Intestinal
Neuroendocrine
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Will Be Recruiting
Condition(s) Treated at Site
Bladder
Non-Small Cell Lung Cancer
Prostate
Small Cell Lung
Head & Neck
Solid Tumor
Digestive & Intestinal
Neuroendocrine