JS212 plus JS001 and 5‑FU for advanced esophageal squamous cell carcinoma

An Open-label, Multicenter, Phase II Clinical Study to Evaluate the Safety and Efficacy of JS212 Combination Therapy in Patients With Advanced Esophageal Squamous Cell Carcinoma (ESCC)

This will test whether combining JS212 with JS001 and 5‑FU helps people with advanced esophageal squamous cell carcinoma who have not had prior systemic anti‑cancer therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 280 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07484724 on ClinicalTrials.gov

What this trial studies

This is an open‑label, multi‑center phase II trial testing the safety and preliminary efficacy of a combination regimen (JS212, JS001, and 5‑FU) in patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma not amenable to curative treatment. Eligible participants are adults 18–75 with histologically confirmed ESCC, at least one measurable lesion by RECIST 1.1, ECOG performance status 0–1, and no prior systemic anti‑tumor therapy (with specified exceptions for prior adjuvant/neoadjuvant therapy). The study will monitor safety, tolerability, and tumor responses using standard imaging and RECIST criteria, with expected follow‑up for preliminary efficacy endpoints. Patients previously treated with anti‑PD‑1/PD‑L1 antibodies or certain ADC therapies are excluded to avoid confounding prior immune or targeted exposures.

Who should consider this trial

Good fit: Adult patients (18–75 years) with histologically confirmed locally advanced, recurrent, or metastatic ESCC, at least one measurable lesion, ECOG 0–1, expected survival ≥12 weeks, and no prior systemic anti‑tumor therapy (or recurrence >6 months after prior adjuvant/neoadjuvant therapy) are ideal candidates.

Not a fit: Patients who previously received anti‑PD‑1/PD‑L1 therapy or ADCs targeting EGFR/HER3 or ADCs with topoisomerase I inhibitors, or those with poor performance status or very limited life expectancy, are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could provide higher tumor response rates and longer disease control for people with advanced ESCC compared with existing single‑agent or chemotherapy options.

How similar studies have performed: Combinations of immune checkpoint inhibitors with chemotherapy have shown improved responses in advanced esophageal squamous cell carcinoma in prior clinical trials, supporting the rationale for this approach.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects aged 18 to 75 years (inclusive) at the time of signing the Informed Consent Form (ICF).
2. Histologically or cytologically confirmed esophageal squamous cell carcinoma (ESCC) that is locally advanced, recurrent, or metastatic, and not amenable to radical treatment.
3. No prior systemic anti-tumor therapy. For patients who received neoadjuvant/adjuvant therapy or radical concurrent chemoradiotherapy, the interval from the last dose of chemotherapy to disease recurrence or progression must be \> 6 months to be eligible for screening.
4. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Expected survival ≥ 12 weeks

Exclusion Criteria:

1. Prior treatment with any of the following: anti-PD-1 or anti-PD-L1 antibody therapy; ADC therapy targeting EGFR and/or HER3, or ADC therapy with a topoisomerase I inhibitor as the toxic payload;
2. Subjects at high risk of bleeding or esophageal fistula, e.g., lesions with large ulcers or direct invasion of vital adjacent organs such as the aorta or trachea;
3. Subjects with a history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose;
4. Presence of active central nervous system (CNS) metastases;
5. Active autoimmune disease requiring systemic therapy (e.g., corticosteroids or immunosuppressive agents) within 2 years prior to the first dose;
6. Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 1 per CTCAE v6.0 or to the level specified in the inclusion/exclusion criteria;
7. Severe cardiovascular or cerebrovascular disease;
8. Known hypersensitivity or severe allergic reaction to the study treatment drugs, any of their components, or their excipients；

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital of Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chengbo Jia

Conditions Advanced Esophageal Squamous Cell Carcinoma