AzTrials
AzTrials

Esophageal Squamous Cell Carcinoma (ESCC)Phase 2NCT07682376

Low-Dose Radiotherapy With Retlirafusp Alfa and Chemotherapy as Neoadjuvant Therapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

A Phase 2 study testing Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin and Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin in people with Esophageal Squamous Cell Carcinoma (ESCC), run by Harbin Medical University at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study aims to evaluate the efficacy and safety of neoadjuvant low-dose radiotherapy combined with Retlirafusp alfa and chemotherapy in the treatment of resectable locally advanced esophageal squamous cell carcinoma. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin and Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
1 siteChina
Study dates
10 Jun 2026to 30 May 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntary participation with written informed consent.
  • Age 18-75 years, male or female.
  • Histologically or cytologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
  • Clinical stage T1-4aN1-3M0 or T3-4aN0M0 (AJCC 9th edition): T stage determined by CT combined with MRI or endoscopic ultrasound; nodal involvement confirmed by biopsy, EBUS/EUS, or mediastinoscopy, or imaging showing lymph node short-axis diameter ≥2.0 cm; distant metastasis (M1) excluded by FDG-PET/CT or chest/abdominal/brain CT/MRI; no suspicious metastatic lymph nodes on cervical ultrasound.
  • Potentially resectable thoracic esophageal lesion with anticipated R0 resection.
  • No prior systemic therapy for esophageal tumor (chemotherapy, targeted therapy, immunotherapy, radiotherapy, etc.).
Show all 14Show fewer
  • ECOG performance status 0-1.
  • At least one measurable lesion per Japanese Classification of Esophageal Cancer, 12th edition.
  • Agreement to provide archived tumor tissue or undergo biopsy for biomarker analysis.
  • Adequate organ function (within 14 days prior to first dose, without blood products or growth factors):
  • Hematology: WBC ≥4×10⁹/L, ANC ≥2×10⁹/L, hemoglobin ≥90 g/L, platelets ≥90×10⁹/L.Hepatic: total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert's syndrome), AST and ALT ≤2.5×ULN (≤5×ULN for liver metastases), alkaline phosphatase ≤3×ULN (≤5×ULN for liver/bone metastases), albumin ≥30 g/L. Renal: serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault formula). Coagulation: INR ≤1.5 (without anticoagulation).
  • Body weight >35 kg, with no >10% weight loss in the past 3 months.
  • Life expectancy >12 months.
  • Women of childbearing potential and men must use effective contraception during the study and for 3 months after the last dose; non-lactating; negative serum/urine HCG within 7 days before first dose for women of childbearing potential.

Who cannot join

  • 1.History of hypersensitivity to any component of Retlirafusp alfa, paclitaxel, carboplatin, or other platinum agents.
  • 2,Cervical esophageal cancer, esophageal adenocarcinoma, or other pathological types.
  • 3.Clinical stage I/IIA, T4b unresectable, or distant metastasis (M1) confirmed by imaging.
  • 4.History of other malignancies within 5 years, except cured basal cell carcinoma of the skin, cervical carcinoma in situ, etc.
  • 5.Prior or current receipt of any of the following:
  • Any radiotherapy, chemotherapy, or other anti-tumor therapy for malignancy.
Show all 17Show fewer
  • Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent) within 2 weeks prior to first study drug administration. Inhaled or topical steroids and adrenal hormone replacement at doses >10 mg/day prednisone or equivalent are permitted in the absence of active autoimmune disease.
  • Receipt of live-attenuated vaccine within 4 weeks prior to first study drug administration.
  • Major surgery or severe trauma within 4 weeks prior to first study drug administration.
  • 6.Active or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy). Patients with psoriasis or childhood asthma/allergy that has fully resolved and requires no intervention in adulthood may be considered; however, those requiring bronchodilators for medical intervention are excluded.
  • 7.Immunodeficiency, including HIV positivity, other acquired or congenital immune deficiencies, or history of organ or allogeneic bone marrow transplantation.
  • 8.Poorly controlled cardiac conditions, including but not limited to: (1) NYHA class ≥II heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias uncontrolled despite intervention.
  • 9.Severe infection (CTCAE grade ≥2) within 4 weeks prior to first study drug administration, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; active pulmonary inflammation on baseline chest imaging; signs/symptoms of infection or need for oral/IV antibiotics within 14 days prior to first dose (except prophylactic antibiotics).
  • 10.Active pulmonary tuberculosis by history or CT, history of active tuberculosis within 1 year prior to enrollment, or history of active tuberculosis >1 year ago without adequate treatment.
  • 11.Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL), or hepatitis C (HCV antibody positive with HCV RNA above the lower limit of detection).
  • 12.Diagnosis of other malignancy within 5 years prior to first study drug administration, except those with low risk of metastasis or death (5-year survival >90%), such as adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ.
  • 13.Pregnant or lactating women. 14.Other conditions deemed by the investigator to potentially necessitate premature study termination, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, alcoholism, drug abuse, or family/social factors that may affect patient safety or compliance.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, China

    Harbin, Heilongjiang, 150081

Other trials in China

About this study

Official title: Low-Dose Radiotherapy Combined With Retlirafusp Alfa and Chemotherapy as Neoadjuvant Therapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: An Exploratory Phase II Study

This study aims to evaluate the efficacy and safety of neoadjuvant low-dose radiotherapy combined with Retlirafusp alfa and chemotherapy in the treatment of resectable locally advanced esophageal squamous cell carcinoma.

Read the detailed description

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China, accounting for approximately 90% of cases. Most patients are diagnosed at locally advanced stages. Although standard neoadjuvant chemoradiotherapy can achieve a pathological complete response (pCR) rate of around 43%, over 30% of patients still experience postoperative recurrence, and non-pCR patients have a poor prognosis. Immunotherapy has opened new avenues for locally advanced ESCC, with neoadjuvant immunochemotherapy achieving pCR rates of approximately 20%-35%, indicating room for further improvement.

Low-dose radiotherapy (LDRT, 8 Gy/4 fractions) can remodel the tumor immune microenvironment, promoting the conversion of "cold tumors" to "hot tumors" and enhancing the antitumor efficacy of immune checkpoint inhibitors. Retlirafusp alfa is an anti-PD-L1/TGF-βRII bifunctional fusion protein developed by Hengrui Medicine, which simultaneously blocks both the PD-L1 and TGF-β signaling pathways, thereby activating T-cell-mediated tumor killing. This study innovatively combines low-dose radiotherapy, Retlirafusp alfa, and chemotherapy to explore its value in the neoadjuvant setting for resectable locally advanced ESCC.

This is a prospective, cohort, phase II clinical trial planned to enroll 96 patients with previously untreated resectable locally advanced ESCC (AJCC 9th edition stage T1-4aN1-3M0 or T3-4aN0M0). Cohort A receives low-dose radiotherapy (8 Gy/4 fractions) combined with Retlirafusp alfa and nab-paclitaxel plus cisplatin/carboplatin for 2 cycles; Cohort B receives Retlirafusp alfa plus nab-paclitaxel and cisplatin/carboplatin (without radiotherapy). Radical surgery is performed 4-6 weeks after neoadjuvant therapy. The primary endpoint is pCR rate. Secondary endpoints include major pathological response (MPR), R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), and safety. This study will provide important evidence for the "low-dose radiotherapy + immunotherapy + chemotherapy" neoadjuvant treatment model in locally advanced ESCC, with the potential to further improve pCR rates and long-term patient survival.

Being tested
Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin, Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin
Keywords
Esophageal Squamous Cell Carcinoma, Retlirafusp alfa, neoadjuvant
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatinDrug

    Low-dose radiotherapy: 8 Gy in 4 fractions, 2 Gy per fraction, targeting the primary tumor and metastatic lymph nodes.

    Retlirafusp alfa: 1800 mg or 30 mg/kg on D1, q3w, for 2 cycles.

    Nab-paclitaxel: 125 mg/m² on D1 and D8, plus cisplatin 75 mg/m² on D1 or carboplatin AUC=5 on D1, q3w, for 2 cycles.

  • Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatinDrug

    Retlirafusp alfa: 1800 mg or 30 mg/kg on D1, q3w, for 2 cycles.

    Nab-paclitaxel: 125 mg/m² on D1 and D8, plus cisplatin 75 mg/m² on D1 or carboplatin AUC=5 on D1, q3w, for 2 cycles.

Study groups in NCT07682376
Study groupRoleWhat they receive
Low-dose radiotherapy + Retlirafusp alfa + chemotherapyExperimentalLow-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin
Receives: Drug: Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin
Retlirafusp alfa + chemotherapyExperimentalRetlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin
Receives: Drug: Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological Complete Response (pCR)

    pCR is defined as the absence of residual invasive carcinoma cells in both the resected primary tumor and lymph nodes.

    Measured: Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

Secondary outcomes (9)

  1. Major Pathological Response (MPR)

    Proportion of patients with ≤10% residual viable tumor cells in the postoperative specimen.

    Measured: Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

  2. R0 Resection Rate

    Proportion of patients achieving radical resection with negative surgical margins (including distal, proximal, and circumferential margins).

    Measured: Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

  3. Objective Response Rate (ORR)

    Proportion of patients achieving complete response (CR) or partial response (PR).

    Measured: Assessed via imaging after completion of neoadjuvant therapy; follow-up up to 6 months.

  4. Disease Control Rate (DCR)

    Proportion of patients achieving CR, PR, or stable disease (SD) sustained for the minimum required duration.

    Measured: Assessed via imaging after completion of neoadjuvant therapy; follow-up up to 6 months.

  5. Event-Free Survival (EFS)

    Time from enrollment to disease progression, inoperability, postoperative recurrence, or death from any cause (whichever occurs first).

    Measured: From enrollment to first event, assessed every 3 months; follow-up up to 36 months.

  6. Overall Survival (OS)

    Time from enrollment to death from any cause.

    Measured: From enrollment to death or last follow-up, assessed every 3 months; follow-up up to 36 months.

  7. Adverse Event Rate

    Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and treatment-related adverse events (TRAEs), graded per NCI-CTCAE v6.0.

    Measured: Continuous monitoring from informed consent to 90 days after the last dose; follow-up up to 36 months.

  8. Quality of Life Assessment Score

    Evaluated using the EORTC QLQ-C30 and QLQ-OES18 questionnaires.

    Measured: Assessed at screening, Cycle 1 Day 1, Cycle 2 Day 1（each cycle is 21 days）, and at 1, 3, 6, and 12 months post-surgery (7 time points in total); follow-up up to 12 months.

  9. Biospecimen collection time points (tissue and blood samples)

    before treatment, after radiotherapy completion, during combination therapy, and after treatment. Biopsy samples (for single-cell sequencing, mIHC, and spatial transcriptomics) and plasma (for Olink/proteomics and metabolomics) to explore biomarkers with potential clinical value.

    Measured: Tissue and blood samples were collected at four time points: before treatment, after radiotherapy, during combination therapy (Cycle 1 Day 1 to Cycle 2 Day 1; 21 days per cycle), and before surgery; follow-up continued up to 6 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2026
  2. Study start10 Jun 2026
  3. Primary completion30 May 2028 (estimated)
  4. Study completion30 May 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07682376
Sponsor's protocol ID
MA-EC-II-032
Status last verified
Jun 2026
First submitted
22 Jun 2026
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin and Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin in people with Esophageal Squamous Cell Carcinoma (ESCC), run by Harbin Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response (pCR) (time frame: Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07682376.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in