The Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With Chemotherapy as the First-line Treatment for Esophageal Squamous Cell Carcinoma

A Clinical Trial to Explore the Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With Chemotherapy as the First-line Treatment for Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

This study is a single-arm clinical trial to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab combined with chemotherapy in the first-line treatment of patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC). After screening and meeting the inclusion criteria, the patients were enrolled and received 6 cycles of Iparomlimab and Tuvonralimab combined with albumin-bound paclitaxel and cisplatin. Subsequently, maintenance treatment was carried out using Iparomlimab and Tuvonralimab ± albumin-bound paclitaxel until disease progression or the occurrence of unacceptable adverse events, with a total maximum treatment duration of 24 months.

The main objective of this study is to: 1. evaluate the ORR of Iparomlimab and Tuvonralimab combined with albumin-bound paclitaxel and cisplatin. 2. The secondary endpoints include PFS, DCR, DoR, OS and safety, etc.

Inclusion Criteria:

1. Age ≥18 years old, gender not limited;
2. Unresectable, recurrent or advanced metastatic esophageal squamous cell carcinoma confirmed by histopathological examination (excluding adenosquamous carcinoma mixed type and other pathological types);
3. For patients who have previously received adjuvant/neoadjuvant chemotherapy/chemoradiotherapy, or radical concurrent chemoradiotherapy , the time from the last treatment to disease recurrence is more than 6 months;
4. ECOG 0-1;
5. According to RECIST v1.1, there is at least one measurable lesion;
6. Be capable of providing newly obtained or archived tissue samples for immunohistochemical analysis of PD-L1 expression;
7. The patient's organ functions are normal, with no serious abnormalities in blood, heart, lung, liver or kidney functions, and no immune deficiency diseases.
8. The patient has normal coagulation function and no active bleeding or thrombotic diseases.
9. Expected survival time ≥12 weeks;
10. Male subjects who are female of childbearing age or whose sexual partners are female of childbearing age must take effective contraceptive measures throughout the treatment period and for 6 months after the treatment period.
11. Voluntarily sign a written informed consent form and be able to comply with the visitation and related procedures stipulated in the plan

Exclusion Criteria:

1. Locally advanced esophageal cancer that can be potentially cured through radical surgical resection or radiotherapy;
2. Esophageal squamous cell carcinoma that is known to have complete obstruction under endoscopy and requires interventional treatment to relieve the obstruction;
3. There is a risk of perforation after stent implantation in the esophageal or tracheal cavity;
4. Has received systemic treatment for advanced or metastatic esophageal squamous cell carcinoma in the past;
5. Other malignant tumors diagnosed within 5 years prior to the first administration, except for effectively treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and/or effectively resected cervical cancer and/or breast cancer in situ;
6. Severe infection occurs (CTCAE>grade 2), or active pulmonary inflammation;
7. Previous or current interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or severe lung function impairment;
8. Patients with active tuberculosis infection;
9. Participate in another interventional clinical study simultaneously, unless participating in an observational (non-interventional) clinical study or being in the follow-up stage of an interventional study;
10. Patients with congenital or acquired immune deficiencies, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the detection limit), or patients with co-infection of hepatitis B and hepatitis C;
11. There is a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
12. Having undergone major surgical operations (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to the first dose of the study treatment or expecting to undergo major surgeries during the study treatment period;
13. It is known that there are symptomatic central nervous system metastases and/or cancerous meningitis (except for stable brain metastases that do not require steroid treatment);
14. It is known that there is an active autoimmune disease requiring symptomatic treatment or a history of the disease within the past 2 years (patients with vitiligo, psoriasis, alopecia or Graves' disease that do not require systemic treatment in the past 2 years, hypothyroidism who only need thyroid hormone replacement therapy, and type 1 diabetes who only need insulin replacement therapy can be enrolled).
15. Female patients who are pregnant or breastfeeding;
16. Any serious or uncontrolled systemic disease that researchers believe may increase the risk of participation in patients