Decitabine Plus Penpulimab as Second-line Therapy for Advanced ESCC Treated With PD-1 Blockade

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

An Single-arm Open-label Phase II Study of Decitabine Plus Penpulimab as Second-line Therapy for Advanced Esophageal Squamous Cell Carcinoma Treated With PD-1 Blockade

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05265962
• Other study ID #: WF-ESCC
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2022
• Source: The First Affiliated Hospital of Zhengzhou University
• Contact: Feng Wang, Doctor
• Phone: 13938244776
• Email: fengw010[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to observe and evaluate the efficacy and safety of Decitabine plus Penpulimab as second-line therapy for advanced esophageal squamous cell carcinoma treated with PD-1 blockade

Description:

Although immune checkpoint inhibitors (ICIs) have been tested in esophageal squamous cell carcinoma(ESCC) with demonstrated clinical efficacy，a significant number of patients have an initial response will develop a secondary resistance and relapse. recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity. These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies. Decitabine is a novel orally active benzamide-type histone deacetylase inhibitor that has shown in vitro activities against a wide array of neoplasms. Hence, the study of decitabine plus penpulimab(AK-105) as second-line therapy for advanced ESCC treated with PD-1 blockade was performed.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 85
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.

2. Age = 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).

3. Histologically confirmed diagnosis of ESCC.

4. Have PD after first-line of PD-1 blockade treatment for unresectable, locally advanced, recurrent or metastatic ESCC.

5. Measurable disease per RECIST v1.1 assessed by the local investigator

6. ECOG PS 0 or 1

7. Newly obtained (preferred) or archival tissue sample available

8. Negative urine or serum pregnancy test within 72 h before randomization (females)

9. Willing to use an adequate method of contraception throughout the study and for 120 days after the last dose of study medication and up to 180 days after the last dose of cisplatin

10. Adequate haematologic function, defined as ANC = 1500/µl, platelet count = 100,000/µl and haemoglobin = 9.0 g/dl or =5.6 mmol/l

11. Adequate renal function, defined as creatinine = 1.5 × ULN or measured or calculated creatinine clearance = 60 mL/min for those with creatinine levels 1.5 × ULN

12. Adequate hepatic function, defined as total bilirubin =1.5 × ULN or direct bilirubin = ULN for those with total bilirubin levels 1.5 × ULN, and ALT/AST levels = 2.5 × ULN

13. Adequate coagulation function, defined as INR = 1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case PT or aPTT should be within the therapeutic range

14. Written informed consent

Exclusion Criteria:

1. Patients with evidence of fistula (either esophageal/bronchial or esophageal/aorta).

2. Evidence of complete esophageal obstruction not amenable to treatment.

3. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.

4. Active autoimmune diseases or history of autoimmune diseases that may relapse

5. Any active malignancy = 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).

6. Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or = Grade 3 hypoalbuminemia = 14 days before initial treatment .

7. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention).

8. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc.

9. Infection (including tuberculosis infection, etc) that requires systemic antibacterial, antifungal or antiviral therapy within 14 days beforeinitial treatment

10. A history of severe hypersensitivity reactions to chidamide and monoclonal antibodies.

11. Patients with toxicities (as a result of prior anticancer therapy) that have not recovered to =Grade 2 or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Decitabine plus Penpulimab
Pts received decitabine 10mg/d IV daily x5 every 3 weeks and penpulimab(AK-105) 200 mg intravenously every 3 weeks until disease progression, unacceptable adverse events (AEs) or withdrawal of consent.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Zhengzhou University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor mutation burden (TMB)	Total number of non-synonymous mutations in each coding region of the tumor genome	up to 24 months
Other	PD-L1 CPS	Number of PD-L1 staining cells (tumor cells)/Total tumor cellsk*100%	up to 24 months
Primary	OS	From date of initial treatment until the date of death from any cause	up to 24 months
Secondary	ORR	Defined as the proportion of patients with a documented complete response, partial response(CR+PR)	up to 24 months
Secondary	PFS	From date of initial treatment until the date of first documented progression or date of death from any cause	Up to 24 months
Secondary	DOR	Refers to the time when the tumor is first evaluated as CR or PR until the first assessment is PD (Progressive Disease) or any cause of death.	up to 24 months
Secondary	DCR	Defined as the proportion of patients with a documented complete response, partial response and stable response(CR+PR+SD)	up to 24 months
Secondary	Adverse Events (Safety)	Adverse Events	up to 24 months