Using sacituzumab govitecan for advanced esophageal squamous cell carcinoma

A Phase II Study of Sacituzumab Govitecan for Advanced Esophageal Squamous Cell Carcinoma Patients

This study is testing a new treatment called sacituzumab govitecan for people with advanced esophageal squamous cell carcinoma whose previous treatments didn’t work, to see if it can help them.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Taiwan University Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation, sacituzumab
• Locations: 1 site (Taipei)
• Trial ID: NCT06329869 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of sacituzumab govitecan in patients diagnosed with advanced esophageal squamous cell carcinoma (ESCC). The study focuses on patients whose tumors overexpress Trop-2, a protein that is believed to play a role in the progression of ESCC. Participants will receive the treatment after failing prior platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. The trial will assess measurable disease outcomes based on established RECIST criteria.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed advanced esophageal squamous cell carcinoma who have previously failed standard therapies.

Not a fit: Patients with early-stage esophageal cancer or those who have not received prior chemotherapy 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 esophageal squamous cell carcinoma who have limited treatment choices.

How similar studies have performed: While the approach of targeting Trop-2 is promising, it is relatively novel in the context of esophageal squamous cell carcinoma, and previous studies have shown varying degrees of success with similar therapies.

Eligibility criteria

Inclusion Criteria:

1. Female or male patients, 18 years of age or older, able to understand and give written informed consent.
2. Histologically proven squamous cell carcinoma of esophagus.
3. Patients with advanced ESCC, defined as those with unresectable locally advanced, recurrent, or metastatic disease, failed prior platinum-based chemotherapy and anti-PD-1/PD-L1 therapy (adjuvant anti-PD-1 therapy considered as prior exposure of anti-PD-1/PD-L1 therapy; progression or recurrence within 6 months of platinum-based chemoradiotherapy for localized disease considered as failed prior platinum-based chemotherapy).
4. Measurable disease as determined by RECIST 1.1. Lesions in previously irradiated areas should not be considered measurable unless they have progressed since the radiotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Archival tumor tissue for Trop-2 expression and optional fresh biopsy if feasible.
7. Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/µL).
8. Adequate hepatic function (bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases, and serum albumin \> 3 g/dL).
9. Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976}.
10. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendices.
11. Willing and able to comply with the requirements and restrictions in this protocol.

Exclusion Criteria:

1. Positive serum pregnancy test or women who are breastfeeding.
2. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
3. Requirement for ongoing therapy with or prior use of any prohibited medications.
4. Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs at the time of study entry.
5. Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent. Patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study. If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
6. Have previously received topoisomerase 1 inhibitors.
7. Have an active second malignancy. Patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed.
8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment.
9. Have active serious infection requiring antibiotics.
10. Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load or taking medications that may interfere with SN-38 metabolism.
11. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.

    1. Patients who test positive for hepatitis B surface antigen (HBsAg) will not be eligible. 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 will require HCV RNA by quantitative PCR for confirmation of active disease.
12. Patients who test positive for HIV antibody.
13. Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
14. Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study.
15. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.
16. No adequate archival or fresh ESCC tumor tissues for characterization of Trop-2 expression.
17. Active central nervous system metastases.
18. Adenocarcinoma of esophagus or gastroesophageal junction

Where this trial is running

Taipei

• National Taiwan University Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Principal investigator: Chih-Hung Hsu, M.D., Ph.D. — National Taiwan University Hospital
• Study coordinator: Chih-Hung Hsu, M.D., Ph.D.

Conditions Esophageal Squamous Cell Carcinoma; sacituzumab govitecan; Trop-2