Sacituzumab Govitecan-Hziy for the Treatment of Patients with Advanced Thymoma or Thymic Carcinoma
This phase II trial tests how well sacituzumab govitecan-hziy works to treat patients with thyroma or thymic carcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP 2 receptors, and delivers govitecan to kill them.
Inclusion Criteria
- Age ≥ 18 years at time of signing informed consent form (ICF)
- Ability to understand and the willingness to sign a written informed consent document
- Patients with histologically confirmed advanced thymoma or thymic carcinoma
- Patients who have experienced disease progression after treatment with at least one prior systemic therapy
- Measurable disease per RECIST v 1.1
- Availability of pre-treatment tumor tissue (archival or fresh); If archival tissue is not available and a fresh biopsy is not considered safe and medically feasible by the Investigator, the patient may be approved for enrollment after consultation with the principal investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/uL) without filgrastim support (obtained within 14 days prior to initiation of study treatment)
- Platelet count ≥ 100 x 10^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
- Hemoglobin (Hgb) ≥ 80 g/L (8 g/dL). Patients may be transfused to meet this criterion (obtained within 14 days prior to initiation of study treatment)
- Aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions (obtained within 14 days prior to initiation of study treatment): * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
- Serum bilirubin ≤ 1.5 x ULN with the following exception (obtained within 14 days prior to initiation of study treatment): * Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN
- Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula) (obtained within 14 days prior to initiation of study treatment)
- For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (obtained within 14 days prior to initiation of study treatment)
- Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below: * Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of study treatment. Women must refrain from donating eggs during this same period. * A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. * Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: * With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 90 days after the final dose of sacituzumab govitecan-hziy. Men must refrain from donating sperm during this this same period. * With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and 90 days after the final dose of sacituzumab govitecan-hziy to avoid potential exposure to the embryo. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the view of the investigator, contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study treatment
- Symptomatic brain metastasis requiring corticosteroids. Patients with treated brain metastases are eligible
- No concurrent therapy with approved or investigational anticancer therapeutics
Additional locations may be listed on ClinicalTrials.gov for NCT06248515.
Locations matching your search criteria
United States
California
Palo Alto
District of Columbia
Washington
PRIMARY OBJECTIVE:
I. To evaluate the clinical efficacy of sacituzumab govitecan (sacituzumab govitecan-hziy) by overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in adult patients with advanced thymoma and thymic carcinoma after progressing on at least one prior line of therapy.
SECONDARY OBJECTIVES:
I. To estimate the progression-free survival (PFS) and overall survival (OS) and to describe the duration of response (DOR), for patients with a response, in thymic epithelial tumor (TET) treated with sacituzumab govitecan-hziy.
II. To assess the safety of sacituzumab govitecan-hziy in TET patients using treatment-emergent adverse events assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
CORRELATIVE OBJECTIVE:
I. To assess Trop-2 expression from archival tissue using immunohistochemistry (IHC) and the association between ORR, PFS, OS, and DOR.
EXPLORATORY OBJECTIVES:
I. To assess for the presence of emerging surface proteins (Surfaceome) for antibody drug conjugates (ADCs) via imaging mass cytometry (IMC) in patients with advanced TET who are treated with sacituzumab govitecan (e.g. HER3, B7-H3, CEACAM5, EGFR, MET).
II. To evaluate Trop-2 expression on circulating tumor cells (CTCs) at baseline, during treatment (cycle 3 day 1 [C3D1]), and at time of progression.
OUTLINE:
Patients receive sacituzumab govitecan-hziy intravenously (IV) over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and collection of blood samples at screening and on study. Patients may undergo biopsy at screening and/or on study.
After completion of study treatment, patients are followed up every 6 months for 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMedStar Georgetown University Hospital
Principal InvestigatorChul Kim
- Primary IDCO-US-979-6770-NCT06248515
- Secondary IDsNCI-2024-06009
- ClinicalTrials.gov IDNCT06248515