Bintrafusp Alfa in Previously Treated Patients With R/M Non-keratinizing NPC

Study Overview
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Brief Summary
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This would be a phase II prospective single arm mono-institutional study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of bintrafusp alfa in previously treated patients with recurrent and metastatic (R/M) non-keratinizing nasopharyngeal carcinoma (NPC).

Detailed Description
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All the patients must be registered with the Investigator(s) prior to initiation of treatment. The registration desk will confirm all eligibility criteria and obtain essential information (including patient number). Patients shall receive Bintrafusp alfa treatment through intravenous therapy every two weeks up until disease progression, unacceptable toxicity or for a maximum of 2 years. Survival Follow-up till 2 years will also be performed.

Official Title
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Phase II Prospective Study of Bintrafusp Alfa in Previously Treated Patients With Recurrent and Metastatic (R/M) Non-keratinizing Nasopharyngeal Carcinoma (NPC)

Conditions
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Nasopharyngeal Carcinoma, Recurrent Carcinoma, Metastatic Cancer, Non-keratinizing Carinoma

Intervention / Treatment
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* Drug: Bintrafusp Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed non-keratinizing differentiated (World Health Organization WHO Type II) or undifferentiated (WHO Type III) nasopharyngeal carcinoma (NPC) that has recurred at regional or / and distant sites Measurable disease according to the RECIST criteria (version 1.1) for the evaluation of measurable disease Received one or more lines of chemotherapy, which must include prior treatment with a platinum agent either for the treatment of metastatic or recurrent disease Experienced progression of disease within 6 months following completion of a platinum-based combination therapy as part of (neo)-adjuvant therapy Male or female subjects with age: 18-79 years old Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 No prior immunotherapy Written informed consent obtained for clinical trial participation and providing archival tumor tissue, if available Females of childbearing potential or non-sterilized male who are sexually active must use a highly effective method of contraception Females of childbearing potential must have negative serum or urine pregnancy test Have life expectancy ≥ 3 months Adequate organ function as defined as: Absolute neutrophil count ≥ 1.5 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin >= 8.0 g/dL, Serum alanine aminotransferase ([ALT]; serum glutamate-pyruvate transferase [SGPT]), or serum aspartate aminotransferase [AST] where available at the center) < 2.5 x upper limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases Serum total bilirubin < 2 x ULN Serum creatinine < 1.5 x ULN Exclusion Criteria: Prior invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured Isolated local recurrence or persistent disease Has disease that is suitable for local therapy administrated with curative intent Severe, active co-morbidity Currently participating in and receiving clinical trial treatment or has participated in a trial of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment Has prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (≤ grade 1 or at baseline) from adverse events due to previous administered agent Untreated active central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms Irritable bowel syndrome or other serious gastrointestinal chronic conditions associated with diarrhea within the past 3 years prior to the start of treatment Known history of testing positive for HIV or known acquired immunodeficiency syndrome. On chronic systemic steroid or any other forms of immunosuppressive medication within 14 days prior to the treatment. Except: Intra-nasal, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection); Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent; Steroids as premedication for hypersensitivity reactions due to bintrafusp alfa Active or prior documented autoimmune or inflammatory disorders in the past 2 years, except diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment Known active hepatitis B or known hepatitis C is detected; subjects who have been treated and now have an undetectable viral load are eligible History of primary immunodeficiency or solid organ transplantation Receipt of live, attenuated vaccine within 28 days prior to the study treatment Active infection requiring systemic therapy Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb) Females who are pregnant, lactating, or intend to become pregnant during their participation in the study Psychiatric disorders and substance (drug/alcohol) abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bintrafusp Alfa<br>Single group assignment of bintrafusp alfa in previously treated patients with recurrent and metastatic (R/M) nonkeratinizing nasopharyngeal carcinoma (NPC) | Drug: Bintrafusp Alfa<br>* Bintrafusp alfa will be administered intravenously every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Objective Tumour Response | To evaluate the objective tumor response (ORR) to bintrafusp alfa in previously treated R/M NPC patients per response evaluation criteria of solid tumor (RECIST) version 1.1 | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free survival assessment | To assess the progression-free survival (PFS) per RECIST version 1.1 | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Time-to-progression (TTP) assessment | To assess the time-to-progression (TTP) per RECIST version 1.1 | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Median Survival | To assess the median survival | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Toxicity and Tolerability measurement | To measure the toxicities and tolerability in previously treated R/M NPC patients receiving bintrafusp alfa with the most updated version of CTCAE criteria | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Objective Response Rate (ORR) | To evaluate ORR, PFS and TTP per immune-related RECIST (irRECIST) | From the date of screening to radiographically documented progression according to irRECIST, assessed up to 2 years | 
| Survival rate assessment | To measure the survival rate in 12 months and 24 months | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Duration of Response (DOR) evaluation | To evaluate the duration of response (DOR) in previously treated R/M NPC patients receiving bintrafusp alfa | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Investigate the relationship between the response to bintrafusp alfa and plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) level | EBV-DNA will be determined using real-time quantitative polymerase chain reaction and the clearance (half-life) during the first 4 weeks of bintrafusp alfa will be measured. The half-life will be correlated with patients ORR, PFS, and OS | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Disease Control Rate (DCR) | Defined as the percentage of patients with a CR, PR, or SD ≥ 6 months per RECIST 1.1 | From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years | 
| Time to Response (TTR) | Defined as the duration to first documented tumor response | From the date of screening to first radiographically documented tumor response according to RECIST 1.1, assessed up to 2 years | 
| Quality of Life (QoL) | To evaluate via the patient-reported EORTC-QLQ-C30 and H&N-35 questionnaires | Every 12 weeks from the date of screening in the first year of study enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent, Metastatic, non-keratinizing, Nasopharyngeal Carcinoma