Treatment for advanced thyroid cancers using sacituzumab govitEcan

A Multicenter, Open Label, Two Cohort, Single Arm, Phase II Study to Evaluate the Efficacy and Safety of the Anti-TROP2 Antibody-drug Conjugate Sacituzumab Govitecan in Patients With Advanced Differentiated and Anaplastic Thyroid Neoplasms.

This study is testing a new drug called sacituzumab govitEcan to see if it can help people with advanced thyroid cancers that don't respond to traditional treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Grupo Espanol de Tumores Neuroendocrinos (Academic / other)
• Drugs / interventions: sacituzumab, Lenvatinib, Cabozantinib, chemotherapy, immunotherapy, sunitinib
• Locations: 11 sites (Barcelona and 10 other locations)
• Trial ID: NCT06235216 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of sacituzumab govitEcan, an antibody-drug conjugate targeting TROP-2, in patients with advanced or metastatic radioactive-iodine refractory differentiated thyroid carcinoma (DTC) and anaplastic thyroid carcinoma (ATC). The study is designed as a multicohort, single-arm trial where patients will receive the treatment intravenously on specific days of a 21-day cycle. The trial aims to enroll up to 21 patients per cohort, monitoring for treatment responses to determine the efficacy of the drug in these specific cancer types.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced radioactive-iodine refractory DTC or ATC who have progressed on prior systemic therapies.

Not a fit: Patients who have not received prior chemotherapy or those with early-stage thyroid cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced thyroid cancers that are resistant to standard therapies.

How similar studies have performed: While this approach is novel for these specific cancer types, similar studies using antibody-drug conjugates have shown promise in other malignancies.

Eligibility criteria

Inclusion Criteria:

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent.
2. Patient is ≥ 18 years of age.
3. Patient has histologically confirmed metastatic or locally advanced unresectable radioactive-iodine refractory differentiated thyroid cancer (cohort A) or anaplastic thyroid carcinoma (cohort B).
4. Prior therapy in each cohort:

   1. Cohort A: Patients must have experienced progression on at least one previous treatment line with approved systemic therapies (Sorafenib, Lenvatinib or Cabozantinib) and a maximum of 3 prior systemic therapies.
   2. Cohort B: Patients should be included in first-line setting or after failure of any systemic therapy (up to 1 prior treatment lines).
5. Patient has radiographically documented and measurable metastatic or locally advanced disease at baseline.
6. An archival tumor tissue sample should be available for submission to the central laboratory for translational studies. If an archival tumor tissue sample is not available, a new biopsy tissue sample should be provided. No central pathological review will be needed to include the patient in the trial.
7. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. The following baseline laboratory data without transfusional support:

   1. Neutrophil count (ANC) ≥ 1,500/mm3.
   2. Platelet count ≥ 100 × 109/L.
   3. Hemoglobin ≥ 9 g/dL.
   4. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN). Note: patients with Gilbert's disease are excluded.
   5. Serum albumin \> 3 g/dL.
   6. Creatinine clearance (CrCl) ≥ 60 mL/min as estimated by the Cockroft-Gault formula or as measured by 24 hour urine collection (GFR can also be used instead of CrCl).
   7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 xULN for patients with liver metastases.
9. Female patients must either:

   1. Be of nonchildbearing potential:

      I)Postmenopausal \*(defined as at least 1 year without any menses) prior to screening , or II) Documented surgically sterile (e.g.hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral tubal occlusion).

      \*Those who are amenorrheic due to an alternative medical cause are not considered postmenopausal and must follow the criteria for childbearing potential subjects.

      OR
   2. If of childbearing potential:

   I) Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, II) And have a negative urine or serum pregnancy test within 7 days prior to Day 1 (females with false positive results and documented verification of negative pregnancy status are eligible for participation), III) And if heterosexually active, agree to abstinence (if in line with the usual preferred lifestyle of the patient) or consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting at screening and throughout the study period and for at least 6 months after the final study drug administration.
10. Female patients must agree not to breastfeed or donate ovules starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
11. Male patients must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
12. Male patients with a partner with childbearing potential, or who is pregnant or breastfeeding must agree to abstinence or use a condom plus 1 form of highly effective birth control throughout the study period and for at least 6 months after the final study drug administration.
13. Patient agrees not to participate in another interventional study while on treatment in the present study.

Exclusion Criteria:

1. Patient has central nervous system (CNS) metastases.
2. Patient has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).

   Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
3. Patient has a history of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.

   Note: Patients with non melanoma skin cancer, curatively treated localized prostate cancer, or carcinoma in situ of any type (if complete resection was performed) are allowed.
4. Patient has known active Hepatitis B or active hepatitis C:

   1. Patients who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
   2. Patients who test positive for HCV antibody. Patients who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Patients with a known history of HCV or a positive HCV antibody test will not require a HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
   3. Patients who test positive for HIV antibody.
5. Patient has a known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
6. Patient has documented history of a cerebral vascular event (stroke or transient ischemic attack), or the following criteria for cardiac disease:

   1. Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
   2. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
   3. New York Heart Association (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction of \< 40%.
7. Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months prior to the first dose of study drug.
8. Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and patients with a history of gastrointestinal obstruction or perforation within 6 months of enrollment.
9. Patient has uncontrolled hypertension or diabetes.
10. Patient has radiotherapy or major surgery within 4 weeks prior to the first dose of study drug.
11. Patients has received a live vaccine within 30 days, or antibiotics within one week prior to the first dose of study drug.
12. Patient has had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to the first dose of study drug.

    Note: Patients participating in observational studies are eligible.
13. Patient has previously received topoisomerase 1 inhibitors.
14. Patient has known hypersensitivity to sacituzumab govitecan or to any excipient contained in the drug formulation.
15. Patient has other underlying medical conditions that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up.

Where this trial is running

Barcelona and 10 other locations

• Hospital Universitari Vall d'Hebron — Barcelona, Spain (Recruiting)
• Complexo Hospitalario Universitario de Ferrol — Ferrol, Spain (Not_yet_recruiting)
• Institut Catala d´Oncologia (ICO) -Hospitalet — Hospitalet de Llobregat (Barcelona), Spain (Recruiting)
• Hospital Clínico San Carlos — Madrid, Spain (Recruiting)
• Hospital Universitario la Paz — Madrid, Spain (Recruiting)
• Hospital Universitario Ramón y Cajal — Madrid, Spain (Not_yet_recruiting)
• MD Anderson Cancer Center Madrid — Madrid, Spain (Recruiting)
• Hospital General Universitario Morales Meseguer — Murcia, Spain (Recruiting)
• Hospital Universitario Central de Asturias — Oviedo, Spain (Recruiting)
• H.U. Marqués de Valdecilla — Santander, Spain (Recruiting)
• Hospital Universitario Miguel Servet — Zaragoza, Spain (Recruiting)

Study contacts

• Study coordinator: A responsible person Designated by the Sponsor

Conditions Differentiated Thyroid Cancer; Anaplastic Thyroid Cancer; TROP-2; sacituzumab govitecan; Antibody-drug conjugate; SN-38