QL1706 Plus Celecoxib in Advanced Esophageal Squamous Cell Carcinoma

The study aims to explore whether the combination of QL1706 and celecoxib can improve the objective response rate in ICI-refractory ESCC. Eligible patients will receive QL1706 (5 mg/kg IV Q3W) and celecoxib (200 mg BID orally) until disease progression, unacceptable toxicity, or up to 2 years. Safety, PFS, OS, and biomarkers such as PD-L1, HER2, IL-6, and IL-8 will also be evaluated.

Inclusion criteria

• Willing and able to provide written informed consent;
• Aged 18 to 75 years, inclusive;
• Histologically or cytologically confirmed unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC);
• Radiologically confirmed disease progression after at least 6 months of prior PD-1/PD-L1 inhibitor-based treatment;
• At least one measurable lesion per RECIST v1.1 criteria;
• Ability to swallow oral medication;
• ECOG performance status of 0-1;
• Estimated life expectancy ≥12 weeks;
• Adequate organ function (without blood transfusion or growth factors within 14 days prior to first dose), including:

ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L; Serum albumin ≥ 30 g/L; TSH ≤ ULN; if abnormal, normal FT3/FT4 is acceptable; Total bilirubin ≤ 1.5 × ULN; ALT/AST ≤ 2.5 × ULN (≤ 5 × ULN if with liver metastases); ALP ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or CrCl ≥ 50 mL/min; INR ≤ 1.5 (if not on anticoagulation);

• Non-sterilized women of childbearing potential and male participants with such partners must agree to use medically approved contraception during and for 3 months after study drug administration. Women must test negative for serum or urine HCG within 7 days prior to first dose and not be breastfeeding.

Exclusion criteria

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• Any active autoimmune disease or history of autoimmune disease (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism); exceptions: childhood asthma fully resolved without treatment or vitiligo;
• Currently using immunosuppressive therapy or systemic corticosteroids >10 mg prednisone/day (or equivalent) within 2 weeks prior to enrollment;
• History of severe allergic reactions to monoclonal antibodies;
• Discontinued prior PD-1/PD-L1 therapy due to treatment-related toxicity;
• Prior exposure to anti-CTLA-4 therapy;
• History or evidence of interstitial lung disease or active non-infectious pneumonitis;
• Known active tuberculosis;
• Known CNS metastases, leptomeningeal disease, or spinal cord compression;
• Other malignancies within 5 years (excluding cured skin basal cell carcinoma or cervical carcinoma in situ);
• Clinically significant cardiac conditions (NYHA ≥ Class II heart failure, unstable angina, MI within 1 year, clinically significant arrhythmias requiring treatment, QTc >450 ms for males or >470 ms for females);
• Clinically significant bleeding within 3 months before enrollment or known bleeding tendency (positive fecal occult blood must be followed by endoscopy if persistent);
• Tumor invading major blood vessels or deemed likely to invade during the study;
• Patients with esophagotracheal or mediastinal fistulas;
• Clinically significant pleural/ascitic/pericardial effusion requiring drainage (if resolved and stable after drainage, enrollment is allowed);
• Arterial or venous thrombotic events within 6 months (e.g., stroke, DVT, PE);
• Known congenital or acquired bleeding disorders;
• Abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months;
• Prior radiotherapy, chemotherapy, or surgery within 4 weeks prior to first study dose (except bone metastasis palliative radiotherapy); biologics within 4 weeks; targeted therapy within 5 half-lives; unresolved toxicities ≥ Grade 2 (except alopecia);
• Active infection or unexplained fever ≥38.5℃ within 7 days prior to first dose;
• Known immunodeficiency (e.g., HIV); active HBV (HBsAg-positive with HBV DNA ≥ 2000 IU/mL); or active HCV infection;
• Prior dual immunotherapy with PD-1 and CTLA-4 antibodies;
• Significant bleeding history within 1 month (e.g., GI bleeding or vasculitis);
• Live vaccine administration within 4 weeks prior to or planned during the study;
• Other conditions deemed by the investigator to interfere with participation or study results (e.g., substance abuse, psychiatric disorders, severe lab abnormalities, or social/family limitations).