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

• ClinicalTrials.gov Identifier: NCT04396886
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2020
• Last Update Posted: October 27, 2022
• Sponsor: The University of Hong Kong
• Collaborator: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Dr. Chi-Leung Chiang, The University of Hong Kong

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma; Recurrent Carcinoma; Metastatic Cancer; Non-keratinizing Carinoma	Drug: Bintrafusp Alfa	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Prospective Study of Bintrafusp Alfa in Previously Treated Patients With Recurrent and Metastatic (R/M) Non-keratinizing Nasopharyngeal Carcinoma (NPC)
• Actual Study Start Date: February 27, 2020
• Actual Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bintrafusp Alfa; Single group assignment of bintrafusp alfa in previously treated patients with recurrent and metastatic (R/M) nonkeratinizing nasopharyngeal carcinoma (NPC)	Drug: Bintrafusp Alfa; Bintrafusp alfa will be administered intravenously every 2 weeks

Outcome Measures

Primary Outcome Measures :

1. Evaluation of Objective Tumour Response [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   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

Secondary Outcome Measures :

1. Progression-Free survival assessment [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To assess the progression-free survival (PFS) per RECIST version 1.1
2. Time-to-progression (TTP) assessment [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To assess the time-to-progression (TTP) per RECIST version 1.1
3. Median Survival [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To assess the median survival
4. Toxicity and Tolerability measurement [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To measure the toxicities and tolerability in previously treated R/M NPC patients receiving bintrafusp alfa with the most updated version of CTCAE criteria
5. Objective Response Rate (ORR) [ Time Frame: From the date of screening to radiographically documented progression according to irRECIST, assessed up to 2 years ]
   To evaluate ORR, PFS and TTP per immune-related RECIST (irRECIST)
6. Survival rate assessment [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To measure the survival rate in 12 months and 24 months
7. Duration of Response (DOR) evaluation [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   To evaluate the duration of response (DOR) in previously treated R/M NPC patients receiving bintrafusp alfa
8. Investigate the relationship between the response to bintrafusp alfa and plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) level [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   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
9. Disease Control Rate (DCR) [ Time Frame: From the date of screening to radiographically documented progression according to RECIST 1.1, assessed up to 2 years ]
   Defined as the percentage of patients with a CR, PR, or SD ≥ 6 months per RECIST 1.1
10. Time to Response (TTR) [ Time Frame: From the date of screening to first radiographically documented tumor response according to RECIST 1.1, assessed up to 2 years ]
    Defined as the duration to first documented tumor response
11. Quality of Life (QoL) [ Time Frame: Every 12 weeks from the date of screening in the first year of study enrolment ]
    To evaluate via the patient-reported EORTC-QLQ-C30 and H&N-35 questionnaires

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong

Sponsors and Collaborators

The University of Hong Kong

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Investigators

• Principal Investigator: Chi Leung Chiang, FRCR; The University of Hong Kong

  Study Documents (Full-Text)

Documents provided by Dr. Chi-Leung Chiang, The University of Hong Kong:

Study Protocol  [PDF] December 1, 2021

More Information

• Responsible Party: Dr. Chi-Leung Chiang, Clinical Assistant Professor, The University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04396886
• Other Study ID Numbers: UW 19-675
• First Posted: May 21, 2020
• Last Update Posted: October 27, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. Chi-Leung Chiang, The University of Hong Kong:

Recurrent; Metastatic; non-keratinizing; Nasopharyngeal Carcinoma

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Recurrence; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases