A Clinical Study of SHR-9839 as Monotherapy or in Combination With Chemotherapy Plus Adebrelimab Versus Chemotherapy Plus Adebrelimab in Patients With Advanced Esophageal Squamous Cell Carcinoma

Official title

A Randomized, Controlled, Open-label, Multicenter Phase II Clinical Study of SHR-9839 as Monotherapy or in Combination With Chemotherapy Plus Adebrelimab Versus Chemotherapy Plus Adebrelimab in Patients With Advanced Esophageal Squamous Cell Carcinoma

Overview

An open-label, multicenter, randomized, phase II clinical trial to evaluate the safety, tolerability and efficacy of SHR-9839(sc) as monotherapy or in combination with chemotherapy plus adebelimab in patients with advanced esophageal squamous cell carcinoma (ESCC).

Interventions

• Drug SHR-9839(sc) for Injection
  SHR-9839(sc) for Injection，dose level 1
• Drug SHR-9839(sc) for Injection、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion
  Safety run-in Stage: SHR-9839(sc) for Injection ,dose level 1 or lower dose、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion; Dose extension Stage: SHR-9839(sc) for Injection,dose according to Safety run-in Stage、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion or Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion

Primary outcome measures

• ORR：Objective Response Rate [Time frame: First administration to end of treatment visit about 1year]

Secondary outcome measures (8)

• DOR：Duration of relief [Time frame: First administration to disease progression about 1 year]
• DCR：Disease Control Rate [Time frame: First administration to disease progression about 1 year]
• PFS：progression-free survival [Time frame: First administration to disease progression about 1 year]
• OS：Overall Survival [Time frame: First administration until participant's death about 2 years]
• DLT：The Dose-Limiting Toxicity [Time frame: Post-dose at day 1 to Day21]
• MTD： The Maximum Tolerated Dose [Time frame: Post-dose at day 1 to Day21]
• AE：Incidence and severity of adverse events [Time frame: Sign the informed consent form until Safety follow-up completed about 1 year]
• ADA ：Anti-Drug Antibody [Time frame: Day1 pre-dose to 30 days after the last dose about 1 year]

Eligibility criteria

Inclusion criteria

• Capable of providing informed consent; has signed and dated the IRB/EC-approved informed consent form, and is willing and able to comply with scheduled study visits, examinations and all other protocol-specified procedures.
• Aged between 18 and 75 years inclusive at the time of informed consent signature, irrespective of gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histopathologically confirmed locally advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
• Expected survival ≥12 weeks.
• Must provide a minimum of 11 formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or unstained tumor slides.
• Females of childbearing potential must agree to use adequate effective contraception from the date of informed consent, throughout study treatment, and for 9 months after the last dose of investigational product, and refrain from oocyte donation during this period (refer to subsequent section for detailed contraceptive requirements).

Exclusion criteria

• Uncontrolled or symptomatic active central nervous system (CNS) metastases without adequate prior treatment.
• History of another concurrent malignant tumor diagnosed within 3 years prior to the first study drug administration.
• Presence of uncontrolled tumor-related pain as assessed by the Investigator.
• Severe cardiovascular or cerebrovascular diseases.
• History of interstitial lung disease (ILD) including idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans organizing pneumonia), drug-induced pneumonitis, radiation pneumonitis requiring steroid therapy; or suspected/unruled-out ILD on screening imaging; or moderate-to-severe pulmonary disease severely impairing respiratory function.
• Severe infection within 4 weeks before study treatment initiation, including but not limited to bacteremia, severe pneumonia or other infectious complications requiring hospitalization; active CTCAE Grade ≥2 infection requiring systemic antibiotics within 2 weeks prior to first dose (subjects on prophylactic antibiotics e.g., for urinary tract infection prophylaxis are eligible).
• History of immunodeficiency including positive HIV serology; active hepatitis B (positive HBsAg at screening plus HBV-DNA ≥2500 copies/mL /500 IU/mL or above local laboratory cutoff); or active hepatitis C (positive anti-HCV plus detectable HCV RNA).
• Active pulmonary tuberculosis within 1 year before enrollment by medical history or imaging; or prior active pulmonary tuberculosis >1 year ago without standardized anti-tuberculosis treatment.
• Toxicities/complications from prior anti-tumor therapies not recovered to NCI-CTCAE Grade ≤1 or levels specified by eligibility criteria; subjects with Grade ≤2 toxicities may enroll if deemed without safety risk by the Investigator.
• Receipt of any systemic anti-cancer therapy within 4 weeks prior to study treatment start.
• Thoracic radiotherapy >30 Gy within 24 weeks, non-thoracic radiotherapy >30 Gy within 4 weeks before first dose; palliative radiotherapy ≤30 Gy within 14 days before first dose (exception: subjects completing brain metastasis radiotherapy ≥14 days prior to first dose are permitted). For prior radioisotope therapy, a washout of at least five half-lives of the radioisotope is required before study enrollment.
• Major organ surgery (excluding core needle biopsy) or significant trauma within 4 weeks before first study drug, or planned elective surgery during trial participation; invasive minor surgery (biopsy, endoscopy, drainage procedure) within 7 days prior to first dose.
• Any other condition judged by the Investigator likely to interfere with trial conduct or subject safety, such as alcohol/drug abuse, uncontrolled severe illness (including psychiatric disorders) requiring concomitant medication, clinically significant abnormal laboratory findings, familial/social issues or other factors compromising subject safety or data integrity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Beijing Cancer Hospital — Beijing
• The First Affiliated Hospital Of Zhengzhou University — Zhengzhou

Identifiers

NCT: NCT07751341 · SHR-9839-206

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗