First-line treatment with iparomlimab and tuvonralimab plus chemotherapy 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 will test whether adding two immunotherapy drugs, iparomlimab and tuvonralimab, to chemotherapy helps people with unresectable, recurrent, or metastatic esophageal squamous cell carcinoma as a first-line treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hebei Medical University Fourth Hospital (other)
• Drugs / interventions: chemotherapy, Iparomlimab, Tuvonralimab
• Locations: 1 site (Shijiazhuang, Hebei)
• Trial ID: NCT07290010 on ClinicalTrials.gov

What this trial studies

This is a single-arm Phase 2 study giving patients six cycles of iparomlimab and tuvonralimab combined with albumin-bound paclitaxel and cisplatin, followed by maintenance iparomlimab and tuvonralimab with or without albumin-bound paclitaxel until disease progression or unacceptable side effects, for up to 24 months. The primary endpoint is objective response rate (ORR), with secondary endpoints including progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. Eligible patients must be adult males with unresectable, recurrent, or metastatic esophageal squamous cell carcinoma, ECOG 0–1, measurable disease by RECIST v1.1, adequate organ function, and able to provide tissue for PD-L1 testing. Treatments are administered at a single center with safety monitoring throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adult men (≥18 years) with unresectable, recurrent, or metastatic esophageal squamous cell carcinoma, ECOG 0–1, at least one measurable lesion, adequate organ function, and available tissue for PD-L1 testing.

Not a fit: Patients unlikely to benefit include those with non-squamous esophageal cancers, recent relapse within 6 months of prior curative therapy, poor performance status, significant organ dysfunction, active bleeding or immune deficiency, or who cannot attend the single study site.

Why it matters

Potential benefit: If successful, this combination could increase tumor response and delay disease progression compared with historical chemotherapy outcomes.

How similar studies have performed: Other trials combining immune checkpoint inhibitors with chemotherapy or dual immune checkpoints have shown promising activity in ESCC, but this exact iparomlimab plus tuvonralimab combination is novel and not yet proven.

Eligibility criteria

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

Where this trial is running

Shijiazhuang, Hebei

• Hebei Medical University Fourth Hospital — Shijiazhuang, Hebei, China (RECRUITING)

Study contacts

• Study coordinator: Shengmian Li

Conditions: Esophageal Squamous Cell Carcinoma, immunotherapy, ESCC, PD-1/CTLA-4