Clinical trial NCT04396886: Bintrafusp Alfa in Previously Treated Patients With R/M Non-keratinizing NPC
Official title: Phase II Prospective Study of Bintrafusp Alfa in Previously Treated Patients With Recurrent and Metastatic (R/M) Non-keratinizing Nasopharyngeal Carcinoma (NPC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Recurrent Carcinoma
Metastatic Cancer
Non-keratinizing Carinoma
Keywords: Recurrent
Metastatic
non-keratinizing
Nasopharyngeal Carcinoma
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
First posted: 2020-05-21
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of Objective Tumour Response
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
Secondary outcomes:
measure: Progression-Free survival assessment
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Time-to-progression (TTP) assessment
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Median Survival
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Toxicity and Tolerability measurement
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Objective Response Rate (ORR)
timeFrame: From the date of screening to radiographically documented progression according to irRECIST, assessed up to 2 years
measure: Survival rate assessment
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Duration of Response (DOR) evaluation
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Investigate the relationship between the response to bintrafusp alfa and plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) level
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years
measure: Time to Response (TTR)
timeFrame: From the date of screening to first radiographically documented tumor response according to RECIST 1.1, assessed up to 2 years
measure: Quality of Life (QoL)
timeFrame: Every 12 weeks from the date of screening in the first year of study enrolment
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: The University of Hong Kong
name: Chi Leung Chiang, FRCR
role: PRINCIPAL_INVESTIGATOR
References: