A Phase I/II, First-in-Human, Open-Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Preliminary Efficacy, and Immunogenicity of TJ102 in Participants With Advanced or Metastatic Ovarian Cancer and Other Solid Tumors.
Study Identifier:
TJ102-I-II-001-G
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Recruiting
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Study Summary
The goal of this clinical trial is to evaluate whether TJ102, an investigational antibody-drug conjugate (ADC), can safely and effectively treat patients with advanced ovarian or other solid tumors. The main objectives of this study are : • To Determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of TJ102 • to show preliminary antitumor activity in patients with advanced ovarian or other solid tumors. Participants will: • Receive intravenous (IV) infusions of TJ102 at escalating dose levels (during dose escalation) or at the selected expansion dose. • Undergo regular tumor imaging to assess response. • Provide blood samples for pharmacokinetics (PK) and biomarker analysis. • Be monitored for side effects and overall tolerability. This study is being conducted in adult patients with advanced or metastatic ovarian or other solid tumors who have exhausted standard treatment options.
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.
Ovarian
Fallopian Tube
Primary Peritoneal
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/II
Sex
Female
Age
18+ years
Study Drug
Drug: EXPERIMENTAL: TJ102
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Drug: TJ102 will be infused intravenously once every 3 weeks. Participants will receive TJ102 at escalating dose levels (during dose escalation) or at the selected expansion dose
Drug: Drug: TJ102
Drug: TJ102 is a CDH6/FRa directed antibody conjugate with dual payloads
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- 1. Has histologically or cytologically documented locally advanced or metastatic high-grade serous epithelial ovarian cancer, including ovarian, fallopian tube, or primary peritoneal carcinoma, that is not amenable to curative surgery or radiotherapy, and has demonstrated radiographic disease progression on the most recent line of systemic therapy.
- 2. Prior exposure to a platinum-containing regimen is mandatory. Platinum-resistant disease is defined as disease progression during or within 6 months following completion of the most recent platinum-containing regimen. Patients with platinum-sensitive disease may be eligible during Phase 1 if they have received at least 2 prior lines of platinum-containing systemic therapy.
- 3. Prior Lines of therapy:
- Subjects must have received at least one (≥1) and no more than four (≤4) prior lines of systemic therapy in the advanced or metastatic setting and have progressed on, been intolerant to, or be ineligible for standard therapies available in their local region. Prior treatment with mirvetuximab soravtansine and/or bevacizumab is permitted but not required, reflecting regional differences in standard of care, regulatory approval status, availability, or access.
- Hormonal therapy and maintenance therapy, including PARP inhibitors or bevacizumab maintenance, are not counted as prior lines of systemic therapy unless administered for treatment of progressive disease.
- 4. Have at least one measurable lesion by RECIST v1.1 (Eisenhauer et al., 2009) for solid tumors;
- 5. ≥18 years old;
- 6. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) of 0 to 1;
- 7. Life expectancy of ≥12 weeks;
- 8. Patients with adequate organ function and the laboratory test criteria specifically defined as follows within 7 days prior to the first dosing;
- Main Patients with locally advanced or metastatic high-grade serous epithelial ovarian cancer (including ovarian cancer, fallopian tube cancer, or primary peritoneal cancer) confirmed by histology or cytology, who are not suitable for radical surgery or radiation therapy, and who show radiographic disease progression after the most recent line of systemic treatment.
- Patients must have previously received platinum-based therapy. Platinum-resistant disease is defined as disease progression occurring during or within 6 months of the completion of the most recent platinum-based therapy. For patients with platinum-sensitive disease, prior to at least two lines of platinum-based systemic therapy may qualify them for enrollment in a Phase I study.
- Prior line of treatment: Phase I study: Subjects must have received at least one first-line (≥1) prior systemic therapy in advanced or metastatic disease and have experienced disease progression, intolerance, or ineligibility for locally available standard treatment. Prior treatment with mirvetuximab soravtansine and/or bevacizumab is permitted but not required, reflecting regional differences in standard treatment, regulatory approval status, availability, or accessibility.
- Age ≥ 18 years old.
- According to RECIST 1.1, the subject must have at least one measurable lesion.
- Eastern Cooperative Oncology Group (ECOG) Performance Status Scale: 0-1.
- Expected survival time ≥ 12 weeks;
- Patients with adequate vital organ function and meeting the following laboratory criteria defined specifically for the 7 days prior to the first dose: a) Liver function: ● AST and ALT ≤ 2.5 × Upper Limit of Normal (ULN); if liver metastasis, AST and ALT ≤ 5 × ULN. ● Total bilirubin (TBIL) ≤ 1.5 × ULN or, for subjects with confirmed Gilbert's syndrome, TBIL ≤ 3 × ULN. ● Albumin ≥ 3 g/dL. b) Coagulation function: ● International Normalized Ratio (INR) ≤ 1.5 × ULN, or ≤ 3 × ULN for patients receiving anticoagulant therapy; ● APTT ≤ 1.5 × ULN. c) Renal function: ● eGFR ≥ 50 mL/min/1.73m2 calculated according to CKD-EPI 2021 (Appendix 2) d) Hematopoietic function: ● Hemoglobin (HGB) ≥ 90 g/L; ● Platelet count (PLT) ≥ 100 × 10⁹/L; ● Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
- Female subjects of reproductive age must have a negative blood pregnancy test within 7 days prior to the first use of the investigational drug. Patients of childbearing potential (both men and women) must agree to use a reliable method of contraception with their partner from the start of the ICF and for 6 months after the last use of the investigational drug.
- I voluntarily participate in this drug clinical trial, understand and sign the informed consent form, and comply with research visits and research-related procedures.
Exclusion criteria
- 1. Has know hypersensitivity to any component of TJ102 or has a history of severe hypersensitivity reactions to other monoclonal antibodies.
- 2. Has received more than two (2) prior antibody-drug conjugate (ADC) therapies in the advanced or metastatic disease setting, including ADCs containing topoisomerase I inhibitor payloads (e.g., SN-38, DXd, exatecan derivatives) or antimicrotubule payloads (e.g., MMAE, DM1/DM4, auristatins, maytansinoids).
- 3. Prior therapy with any antibody-drug conjugate (ADC) whose cytotoxic payload is eribulin or a structural derivative thereof is prohibited in the advanced/metastatic disease setting.
- 4. 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, 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 TJ102; Has received anti-tumor herbal medicine within 14 days prior to first dose of TJ102;
- 5. Has received a strong or moderate CYP3A4 inhibitor within 3 half-lives prior to first dose of TJ102;
- 6. Received an investigational drug within 28 days or 2 half-lives (whichever is shorter) prior to first dose of TJ102; Current participation in other interventional clinical studies (participation in survival follow-up is allowed);
- 7. Toxic effects of prior anti-tumor therapy have not recovered to NCI-CTCAE V6.0 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 per the discretion of the Investigator;
- 8. 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;
- 9. 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;
- 10. Presence of Grade ≥2 or history of Grade ≥3 peripheral neuropathy.
- 11. Uncontrolled or significant cardiovascular disease
- 12. For patients with documented positive virology status, as confirmed by Screening hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) 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+), should 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.
- 13. 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 and who received prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease) within two weeks prior to starting study treatment.
- 14. 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 (i.e., 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). Subjects with untreated CNS metastases are excluded.
- 15. Other malignancies within 3 years prior to initiation of study treatment (Note: does not include tumors with a negligible risk for metastasis or death, eg, 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 without evidence of disease recurrence);
- 16. Female patients who are lactating or breastfeeding;
- 17. 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. Known allergy to any component of TJ102 formulation, or a history of severe allergic reactions to other monoclonal antibodies;
- Patients who have previously received two (2) or more antibody-drug conjugates (ADCs) in the context of advanced or metastatic disease, including ADCs containing topoisomerase I inhibitor payloads (e.g., SN-38, DXd, ethiotecan derivatives) or antimicrotubule payloads (e.g., MMAE, DM1/DM4, olritamines, maytansines).
- In the context of advanced/metastatic disease, any antibody-drug conjugate (ADC) therapy with a cytotoxic payload of eribulin or a structural derivative thereof is contraindicated.
- Patients who have received mitomycin C and nitrosoureas within 6 weeks prior to the first dose of TJ102; patients who have received oral Fluorouracil(such as S-1, capecitabine) or palliative radiotherapy within 2 weeks prior to the first dose of TJ102; patients who have received other chemotherapy, biotherapy, immunotherapy, major surgery, radical radiotherapy, targeted therapy (including small molecule tyrosine kinase inhibitors), or other antitumor treatments within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of TJ102; and patients who have received antitumor herbal treatments within 14 days prior to the first dose of TJ102.
- Received potent or moderate CYP3A4 inhibitors within 3 half-lives;
- Those who have received other unmarketed investigational drugs within 28 days or two half-lives (whichever is shorter) before the first dose of TJ102, or who are currently participating in other interventional clinical studies (excluding those in the survival follow-up phase);
- Students whose toxicities from previous anti-tumor treatments have not recovered to grade 1 (excluding alopecia and hyperpigmentation) according to the National Cancer Institute Common Terminology of Adverse Events (NCI CTCAE) version 6.0. Students with irreversible toxicities from previous anti-tumor treatments (such as hearing impairment) may be enrolled if, in the investigator's judgment, they do not increase the safety risk.
- Those with a history of (non-infectious) interstitial lung disease (ILD) requiring steroid treatment, currently suffering from or whose imaging studies at the time of screening could not rule out ILD/non-infectious pneumonia.
- The patient presented with severe dry eye syndrome, severe keratitis, severe conjunctivitis, and other serious conditions that researchers determined could increase the risk of corneal epithelial damage.
- The patient has grade 2 or higher peripheral neuropathy, or has a history of grade 3 or higher peripheral neuropathy.
- Uncontrolled or clinically significant cardiovascular disease, including but not limited to: ● Prolonged mean corrected QT interval, QTc > 470 ms in men or women. ● Occurrence of unstable angina, acute myocardial infarction, or congestive heart failure (NYHA class II to IV heart disease) within the 6 months prior to study treatment. ● Clinically significant arrhythmias or other risk factors for torsades de pointes (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 medications.
- For patients with a confirmed virological status positive by screening tests for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), the following patients may be eligible for enrollment in the study, as evaluated by the sponsor and investigators: ● Patients with active hepatitis B: HBV DNA ≤ 500 IU/mL during screening. ● Patients with positive hepatitis C virus antibodies (HCV Ab+) whose infection should be controlled (PCR showing HCV RNA ≤ ULN at screening, either in spontaneous remission or in response to previously successful anti-HCV therapy). Patients with controlled infection must have their HCV RNA monitored regularly, as advised by their attending physician.
- Comorbid severe infections, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia within 4 weeks prior to the start of study treatment; or receiving therapeutic oral or intravenous antibiotics or prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease) within 2 weeks prior to the start of study treatment.
- Active central nervous system (CNS) or meningeal metastases. Subjects with CNS metastases who have received adequate local treatment, have maintained clinical stability for at least 4 weeks (imaging showing no progression of brain lesions and stable neurological symptoms), and have a prednisone dose ≤20 mg/day (or equivalent dose) are eligible to participate in the study. Subjects with untreated CNS metastases are excluded.
- Having other malignancies within 3 years prior to starting TJ102 treatment (Note: This excludes tumors with negligible risk of metastasis or death, such as non-melanoma basal cell carcinoma or squamous cell carcinoma of the skin, breast/cervical carcinoma in situ, and superficial bladder cancer that has received radical treatment and has no evidence of disease recurrence).
- Women who are lactating or breastfeeding.
- Researchers assessed that the subjects had other factors that could affect the research results or interfere with their participation in the entire research process, including past or present physical conditions, treatments or abnormal laboratory test results, and the subjects might not be able to comply with the various procedures, restrictions and requirements of the research.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal
Location
START New York (Long Island)
Lake Success, NY, United States, 11042
Investigator
Geraldine O'Sullivan Coyne
Status
Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Jose Pacheco
Status
Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal