Clinical trial NCT03833661: M7824 Monotherapy in Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer)
Official title: A Phase II, Multicenter, Open-label Study to Investigate the Clinical Efficacy of M7824 Monotherapy in Participants With Locally Advanced or Metastatic Biliary Tract Cancer Who Fail or Are Intolerant to First-line Platinum-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Keywords: M7824
Bintrafusp alfa (proposed INN)
Transforming growth factor-beta
First-line Platinum-Based Chemotherapy
Programmed death-ligand 1
Metastatic Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder cancer
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2019-02-07
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study to evaluate M7824 monotherapy in participants with advanced or metastatic biliary tract cancer (BTC) who failed or were intolerant to first-line (1L) chemotherapy.


Eligibility criteria: Inclusion Criteria

* Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC.
* Availability of tumor (primary or metastatic) archival material or fresh biopsies is mandatory
* Participants with BTC must have failed or be intolerant to 1L systemic platinum-based chemotherapy administered for locally advanced or metastatic disease. Only one prior treatment line is allowed
* Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
* Life expectancy \>= 12 weeks as judged by the Investigator
* Adequate hematological function defined by white blood cell (WBC) count \>= 3 \* 10\^9/Litre with absolute neutrophil count (ANC) \>= 1.5 \* 109/Litre, lymphocyte count \>= 0.5 \* 10\^9/Litre, platelet count \>=75 \* 10\^9/Litre, and hemoglobin (Hgb) \>= 9 grams/decilitre
* Adequate hepatic function defined by a total bilirubin level =\< 1.5 \* upper limit of normal (ULN), an aspartate aminotransferase (AST) level =\< 2.5 \* ULN, and an alanine aminotransferase (ALT) level =\<2.5 \* ULN. For participants with liver involvement in their tumor, AST =\< 5.0 \* ULN and ALT =\< 5.0 \* ULN is acceptable
* Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) =\< 1.5 \* ULN unless the participant is receiving anticoagulant therapy
* Albumin \>= 3.0 grams/decilitre
* Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
* Adequate renal function defined by either creatinine =\< 1.5 \* ULN or an estimated creatinine clearance (CCr) \> 40 milliliter (mL) per minute (min) according to the Cockcroft-Gault formula or by measure of CCr from 24-hour urine collection
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Ampullary cancer was excluded
* Significant acute or chronic infections
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Interstitial lung disease or its history
* Participants who were not eligible for or have not been treated with 1L systemic chemotherapy
* Anticancer treatment within 21 days before the start of study intervention
* Concurrent treatment with nonpermitted drugs
* Prior participation in a M7824 clinical trial
* Prior therapy with other immunotherapy or checkpoint inhibitors, such as anti-PD 1, anti PD L1, anti- cytotoxic T-cell lymphocyte-4 (CTLA-4) antibodies.
* Pregnancy or breast feeding
* Systemic anticancer treatment after failing 1L platinum-based chemotherapy
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first treatment up to 555 days
Secondary outcomes:
measure: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first documentation of objective response to data cutoff (assessed up to 736 days)
measure: Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
timeFrame: Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)
measure: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
timeFrame: Time from first documentation of objective response to data cutoff (assessed up to 736 days)
measure: Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
timeFrame: Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)
measure: Overall Survival (OS)
timeFrame: Time from first administration of study drug to data cutoff (assessed up to 736 days)
measure: Serum Pre-Dose Concentrations (Ctrough) of M7824
timeFrame: At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421 and Day 505
measure: Serum Concentration at End of Infusion (CEOI) of M7824
timeFrame: At Day 1 and Day 29
measure: Number of Participants With Positive Antidrug Antibodies (ADA)
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Percentage of Participants With Confirmed Objective Response as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) According to Microsatellite Instability (MSI) Status
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first documentation of objective response to data cutoff (assessed up to 736 days)
measure: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite Instability (MSI) Status
timeFrame: Time from first documentation of objective response to data cutoff (assessed up to 736 days)
measure: Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
measure: Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite Instability (MSI) Status
timeFrame: Time from first treatment to data cutoff (assessed up to 736 days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: San Francisco
country: United States
facility: UCSF Mount Zion Medical Ctr
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida - Department of Neurology
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute, Inc
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Houston
country: United States
facility: MD Anderson Cancer Center - Unit
state: Texas
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Harbin
country: China
facility: Affiliated Tumor Hospital of Harbin Medical University
city: Pessac Cedex
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut Lévêque - Service Hepato Gastroentérologie Oncologie Digest
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Unita' Operativa di Pediatria
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori Milano
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital - Dept of Oncology
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital - Dept of Gastroenterology
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital - Dept of Oncology
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1):e000564. doi: 10.1136/jitc-2020-000564.