Cadonilimab/Anlotinib in Locally Advanced or Relapsed/Metastatic ESCC Patients After Failure of PD-1 Combined With Platinum-containing Chemotherapy

NCT05990231 | Unknown Phase 2

• 1 other identifier: 2023-0563
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Advanced esophageal squamous cell carcinoma patients who have failed first-line PD-1 inhibitor combined with chemotherapy lack a standard treatment option. Second-line treatments have limited efficacy, indicating a significant unmet clinical need. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) has anti-tumor angiogenesis and tumor growth inhibition effects. Cadonilimab is a human immunoglobulin (Ig) G1 monoclonal antibody (mAb), which is a bispecific antibody that blocks both PD-1 and CTLA-4. Both of them have shown certain efficacy and good safety in more than second-line therapy for patients with advanced esophageal squamous cell carcinoma as monotherapy. This study aims to evaluate the efficacy and safety of cadonilimab combined with anlotinib in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma who have progressed on PD-1 inhibitor combined with platinum-containing chemotherapy.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Squamous Cell Carcinoma; Cadonilimab; Anlotinib; CTLA-4; PD-1

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The proportion of patients whose tumor volume reduced by 30% and could maintain for more than 4 weeks, that is, the sum of the proportion of complete remission (CR) and partial remission (PR)

  2 years

Secondary Outcomes (5)

• Disease control rate （DCR)

  2 years

• Duration of Response(DOR)

  2 years

• Progression-Free-Survival （PFS）

  2 years

• Overall survival (OS)

  2 years

• Adverse events

  2 years

Study Arms (1)

Cadonilimab combined with anlotinib

EXPERIMENTAL

Drug: Cadonilimab combined Anlotinib

Interventions

Cadonilimab combined Anlotinib DRUG

Cadonilimab: intravenous administration at a dose of 10mg/kg on day 1 of each cycle, every 3 weeks (Q3W) Anlotinib: 12mg, orally once a day (orally before breakfast, the daily medication time should be as the same as possible), continuous taking for 2 weeks, stopping for 1 week, 3 weeks (21 days) as a treatment cycle

Cadonilimab combined with anlotinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign a written informed consent form.
• Age ≥18 and ≤80 years, both males and females are eligible.
• ECOG performance status score of 0 or 1.
• Expected survival≥3 months.
• Patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma confirmed by histology and/or cytology that is incurable (including curative surgery and curative radio/chemotherapy). Patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma who have failed of PD-1 inhibitor combined with platinum-based chemotherapy , and are not allowed to receive other systemic anti-tumor treatments. Note: For patients who have received adjuvant/neoadjuvant PD-1 inhibitor combined with platinum-based chemotherapy for non-metastatic disease with curative intent, or curative platinum-based radio/chemotherapy combined with PD-1 inhibitor for locally advanced or recurrent/metastatic disease, if disease progression occurs within \<6 months after the end of the last treatment, and the patients has not received other systemic anti-tumor treatments after disease progression, they are allowed to be enrolled.
• According to RECIST v1.1, patients must have at least one measurable lesion. For patients who have received radiotherapy previously and have no other target lesions available, when there is objective evidence of significant progression after radiotherapy, the lesion treated with radiotherapy can be considered as a target lesion.
• The function of important organs meets the following requirements (excluding any blood components and growth factors used within 14 days):
• Normal bone marrow function, neutrophils ≥1,500/mm3, platelet count ≥100,000/mm3, hemoglobin ≥5.6 mmol/L (9g/dL);
• Normal renal function or serum creatinine ≤1.5 mg/dL and/or creatinine clearance rate ≥60 ml/min;
• Normal liver function or bilirubin ≤1.5 times ULN, ASAT \& ALST ≤1.5 times ULN.
• Female patients of childbearing potential must undergo a urine or serum pregnancy test within the first 3 days before the first dose (if the urine pregnancy test result cannot be confirmed as negative, a serum pregnancy test must be performed, and the serum pregnancy result will prevail), and the result must be negative. If a female patient of childbearing potential has sexual intercourse with an uncircumcised male partner, the subject must take effective contraceptive measures from the beginning of screening and must agree to continue using contraceptive methods for 120 days after the last dose of study drug; whether to stop contraception after this time point should be discussed with the investigator.
• If an uncircumcised male subject has sexual intercourse with a female partner of childbearing potential, the subject must take effective contraceptive measures from the beginning of screening until 120 days after the last dose; whether to stop contraception after this time point should be discussed with the investigator.
• The patient is willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other requirements of the study.

You may not qualify if:

• Subjects who meet any of the following criteria will be ineligible to participate in this study:
• Subjects who have had other malignant tumors within 3 years prior to enrollment, except those who have been cured by local treatment such as basal or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
• Subjects who are concurrently enrolled in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study.
• Subjects who have received systemic anti-tumor therapy (chemotherapy, immunotherapy, etc.) for non-target lesions within 3 weeks before the first dose of study drug; palliative local therapy for non-target lesions within 2 weeks before the first dose of study drug; non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for thrombocytopenia) within 2 weeks before the first dose of study drug; or Chinese herbal medicine or traditional Chinese medicine with anti-tumor indications within 1 week before the first dose of study drug.
• Subjects who have received any treatment targeting tumor immune mechanisms, such as immunotherapy other than PD-1 inhibitors (including immune checkpoint inhibitors such as anti-CTLA-4 antibodies, anti-CD47 antibodies, anti-SIRPα antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, biologics, etc., other than PD-1 inhibitors.
• Subjects who have experienced any of the following during previous PD-1 inhibitor treatment:
• Grade 3 or higher irAE caused by PD-1 inhibitor treatment (excluding endocrine system-related irAEs), irAEs that led to permanent discontinuation of treatment, grade 2 immune-related cardiac toxicity or any grade of neurologic or ophthalmologic irAE.
• All adverse events during previous PD-1 inhibitor treatment have not been completely resolved or resolved to grade 1 before screening for this study. For subjects with grade ≥2 endocrine adverse events, if the condition is stable with appropriate alternative treatment and asymptomatic, enrollment is allowed.
• Previous adverse events that required the use of immunosuppressive agents other than glucocorticoids or recurrence of adverse events during previous immunotherapy that required systemic use of glucocorticoids.
• Screening imaging shows that the tumor surrounds or invades important blood vessels or organs (such as the heart and pericardium, trachea, aorta, superior vena cava, etc.), or there is obvious necrosis or cavity, and the investigator judges that entering the study would increase the risk of bleeding; there are subjects at risk of developing esophagotracheal fistula or esophageal pleural fistula.
• Subjects who have had active autoimmune diseases requiring systemic treatment in the past two years (such as use of disease-modifying drugs, corticosteroids, immunosuppressive therapy), and replacement therapy (such as thyroid hormone, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment.
• Subjects with non-infectious pneumonia/interstitial lung disease (including radiation pneumonitis) requiring systemic glucocorticoid therapy that is currently uncontrolled.
• Presence of brainstem, meningeal metastasis, spinal cord metastasis or compression.
• Presence of active central nervous system (CNS) metastatic lesions. Note: Subjects with previously treated brain metastases (such as surgery or radiotherapy) are allowed to enroll if they are clinically stable for at least 2 weeks (from the time of first administration of study drug) and have discontinued corticosteroid hormones for 7 days before administration of study drug; untreated asymptomatic brain metastases (i.e., no neurological symptoms, no need for corticosteroid hormones, no brain metastases with a long axis \>1.5 cm and no obvious peritumoral edema) are eligible to enroll.
• Presence of pleural effusion, pericardial effusion or ascites with clinical symptoms or requiring repeated drainage.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Diabetes Mellitus, Insulin-Dependent, 12

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Hong Shen, MD

  2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Shen, MD

CONTACT

+86 13857136137; shenhong0023@zju.edu.cn

Jing Zhao, MD

CONTACT

+86 13958122786; jingzhao@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2023
• First Posted: August 14, 2023
• Study Start: September 1, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 11, 2023

Record last verified: 2023-08

Locations

CN (1)