Endostatin Adenovirus With Checkpoint Inhibitor in Advanced Head and Neck or Esophageal Cancer

A Phase I, Open-label, Two-cohort Study of Recombinant Human Endostatin Adenovirus in Combination With Immune Checkpoint Inhibitors in Patients With Recurrent or Metastatic Head and Neck Cancer or Esophageal Squamous Cell Carcinoma

This is a Phase I, open-label, dual-cohort clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of intratumoral injection of recombinant human endostatin adenovirus in combination with a PD-1 inhibitor in patients with recurrent or metastatic head and neck cancer, or in patients with esophageal squamous cell carcinoma (ESCC) with superficial lymph node metastasis.

Cohort A will enroll patients with recurrent or metastatic head and neck cancer. Cohort B will enroll patients with ESCC with superficial lymph node metastasis. Both cohorts will receive intratumoral injection of recombinant human endostatin adenovirus combined with intravenous an immune checkpoint inhibitor.

The primary objectives are to assess the safety profile, incidence of dose-limiting toxicities (DLTs), and treatment-related adverse events (TRAEs) of the combination therapy. The secondary objectives include evaluation of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Each cohort plans to enroll approximately 20 patients, with a total of 40 participants.

• Cohort A (Head and Neck Cancer)
• Cohort B (Esophageal Squamous Cell Carcinoma)

Inclusion Criteria:

1. Age ≥18 years

   • Cohort A (Head and Neck Cancer): ≤70 years
   • Cohort B (Esophageal Squamous Cell Carcinoma): ≤75 years

2. Histologically or cytologically confirmed recurrent or metastatic:

   • Cohort A: Head and Neck Cancer
   • Cohort B: ESCC, AJCC 9th edition stage IV

3. Prior treatment:

   • Cohort A: ≥1 prior platinum-based chemotherapy regimen or platinum-refractory/intolerant
   • Cohort B: Prior immune checkpoint inhibitor (ICI) therapy with documented acquired resistance after prior PR or SD

4. At least one lesion accessible for intratumoral injection

   • Cohort A: measurable lesion ≥2 cm by RECIST 1.1
   • Cohort B: superficial metastatic lymph nodes (cervical or supraclavicular)

5. ECOG performance status

   • Cohort A: 0-2
   • Cohort B: 0-1

6. Adequate organ function

7. Life expectancy ≥12 weeks (Cohort A)

8. No anti-tumor therapy (chemotherapy, radiotherapy, biotherapy, antiviral) within 4 weeks prior to enrollment (Cohort A)

9. Availability of fresh tumor tissue specimen or pathological slides from the injection target lesion (Cohort B)

10. Male/female patients of childbearing potential must use effective contraception during study and for at least 6 months after treatment

11. Voluntary participation with signed informed consent

Exclusion Criteria:

1. Known allergy or hypersensitivity to study drugs
2. Lesions unsuitable for injection due to proximity to major blood vessels, nerves, or hollow organs, or with extensive necrosis
3. Deeply located lesions with high procedural difficulty (Cohort B)
4. Concurrent radiotherapy to target lesion(s) (Cohort A)
5. Prior anti-angiogenic therapy (Cohort A)
6. Immunosuppressive therapy or systemic corticosteroids >10 mg/day prednisone (or equivalent) within 2 weeks prior to enrollment
7. Active autoimmune disease or history of autoimmune disease
8. Congenital or acquired immunodeficiency
9. Severe coagulopathy, bleeding tendency, or high-risk lesions (Cohort B)
10. Poor nutritional status (Cohort B)
11. Interstitial lung disease with symptoms or radiographic evidence (Cohort B)
12. Severe uncontrolled systemic disease or recent myocardial infarction (<3 months)
13. Acute infection
14. Pregnancy or breastfeeding
15. Other malignancy besides ESCC (Cohort B)
16. Patients unlikely to comply with follow-up or participation requirements
17. Any condition deemed unsuitable for enrollment by the investigator