Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006)

NCT ID: NCT06143748

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-02
• Study Completion Date: 2027-12-31

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, as high as more than 40% of patients with esophageal cancer experienced locoregional recurrence after definitive CRT. Immune checkpoint inhibitors targeting PD-1/PD-L1 and/or CTLA-4 have shown substantial clinical benefits in advanced esophageal cancer. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in esophageal cancer. The aim of this study was to evaluate the efficacy and safety of cadonilimab (a bispecific PD-1/CTLA-4 antibody) combined with induction chemotherapy followed by definitive radiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Detailed Description

A total of 46 patients with unresectable, locally advanced ESCC will be enrolled to receive cadonilimab plus induction chemotherapy followed by definitive radiotherapy and then 12 additional cycles of maintenance therapy with cadonilimab.

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135 mg/m2, cisplatin 75 mg/m2, and cadonilimab 10 mg/kg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with 2 cycles of cadonilimab. After the completion of radiotherapy, patients will then receive 12 additional cycles of cadonilimab.

Conditions

Esophagus Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The study group

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135 mg/m2, cisplatin 75 mg/m2, and cadonilimab 10 mg/kg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with 2 cycles of cadonilimab. After the completion of radiotherapy, patients will then receive 12 additional cycles of cadonilimab.

Group Type: EXPERIMENTAL

Cadonilimab

Intervention Type: DRUG

Patients received cadonilimab 10 mg/kg every 3 weeks for up to 16 cycles.

Paclitaxel and cisplatin

Intervention Type: DRUG

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will not receive chemotherapy during radiotherapy.

intensity-modulated radiotherapy

Intervention Type: RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Interventions

Cadonilimab

Patients received cadonilimab 10 mg/kg every 3 weeks for up to 16 cycles.

Intervention Type: DRUG

Paclitaxel and cisplatin

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will not receive chemotherapy during radiotherapy.

Intervention Type: DRUG

intensity-modulated radiotherapy

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Intervention Type: RADIATION

Other Intervention Names

AK104; taxol, DDP; IMRT

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed squamous cell carcinoma of the esophagus;

2. Locally advanced, and absence of distant metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan, stage II-IVA (according to UICC TNM version 8);

3. Not suitable for surgery (either for medical reasons or patient's choice);

4. Age at diagnosis 18 to 75 years;

5. No prior cancer therapy;

6. Estimated life expectancy >6 months;

7. Eastern Cooperative Oncology Group performance status ≤ 2

8. No history of concomitant or previous malignancy;

9. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate >60 mL/min;

10. Ability to understand the study and sign informed consent.

Exclusion Criteria

1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);

2. Patients with distant metastasis disease or esophageal fistula at diagnosis;

3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;

4. Patients who have a preexisting or coexisting bleeding disorder;

5. Female patients who are pregnant or lactating;

6. Inability to provide informed consent due to psychological, familial, social and other factors;

7. Presence of CTC grade ≥2 peripheral neuropathy;

8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer

9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;

10. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.

11. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;

12. A history of interstitial lung disease or non-infectious pneumonia;

13. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;

14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Mian XI

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mian Xi, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

References

Gao X, Xu N, Li Z, Shen L, Ji K, Zheng Z, Liu D, Lou H, Bai L, Liu T, Li Y, Li Y, Fan Q, Feng M, Zhong H, Huang Y, Lou G, Wang J, Lin X, Chen Y, An R, Li C, Zhou Q, Huang X, Guo Z, Wang S, Li G, Fei J, Zhu L, Zhu H, Li X, Li F, Liao S, Min Q, Tang L, Shan F, Gong J, Gao Y, Zhou J, Lu Z, Li X, Li J, Ren H, Liu X, Yang H, Li W, Song W, Wang ZM, Li B, Xia M, Wu X, Ji J. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol. 2023 Oct;24(10):1134-1146. doi: 10.1016/S1470-2045(23)00411-4.

Reference Type: RESULT

PMID: 37797632 (View on PubMed)

Frentzas S, Gan HK, Cosman R, Coward J, Tran B, Millward M, Zhou Y, Wang W, Xia D, Wang ZM, Li B, Xia M, Desai J. A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. Cell Rep Med. 2023 Nov 21;4(11):101242. doi: 10.1016/j.xcrm.2023.101242. Epub 2023 Oct 17.

Reference Type: RESULT

PMID: 37852261 (View on PubMed)

Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.

Reference Type: RESULT

PMID: 35108470 (View on PubMed)

Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.

Reference Type: RESULT

PMID: 36990609 (View on PubMed)

Other Identifiers

B2023-425

Identifier Type: -

Identifier Source: org_study_id