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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04066491




Registration number
NCT04066491
Ethics application status
Date submitted
22/08/2019
Date registered
26/08/2019
Date last updated
12/10/2020

Titles & IDs
Public title
Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L Biliary Tract Cancer (BTC)
Scientific title
A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer
Secondary ID [1] 0 0
2019-001992-35
Secondary ID [2] 0 0
MS200647_0055
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Cholangiocarcinoma 0 0
Gallbladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bintrafusp alfa
Treatment: Drugs - Placebo
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin

Experimental: Safety Run-In Part: Bintrafusp alfa + Gemcitabine + Cisplatin -

Experimental: Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin -

Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin -


Treatment: Drugs: Bintrafusp alfa
Participants will receive Bintrafusp alfa intravenously at a dose of 2400 milligram (mg) once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal or for 2 years after the first onset of Complete Response (CR).

Treatment: Drugs: Placebo
Participants will receive Bintrafusp alfa matched Placebo intravenously once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal or for 2 years after the first onset of CR.

Treatment: Drugs: Gemcitabine
Gemcitabine will be received intravenously at a dose of 1000 milligram per meter square (mg/m^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).

Treatment: Drugs: Cisplatin
Cisplatin will be received intravenously at a dose of 25 mg/m^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-in Part: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period
Timepoint [1] 0 0
Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Primary outcome [2] 0 0
Double-blinded Part: Overall Survival (OS)
Timepoint [2] 0 0
First dose of study intervention up to 4 years
Secondary outcome [1] 0 0
Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events
Timepoint [1] 0 0
First dose of study intervention up to 4 years
Secondary outcome [2] 0 0
Safety Run-in Part: Number of Participants with Abnormalities (Grade >= 3) in Laboratory Tests
Timepoint [2] 0 0
First dose of study intervention up to 4 years
Secondary outcome [3] 0 0
Double-blinded: Confirmed Objective Response (COR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
Timepoint [3] 0 0
First dose of study intervention up to 4 years
Secondary outcome [4] 0 0
Double-blinded Part: Duration of Response (DOR) Assessed From Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator or Death
Timepoint [4] 0 0
Time from CR or PR up to 4 years
Secondary outcome [5] 0 0
Double-blinded Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
Timepoint [5] 0 0
First dose of study intervention up to 4 years
Secondary outcome [6] 0 0
Double-blinded Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment Related Adverse Events and Adverse Events of Special Interest (AESI)
Timepoint [6] 0 0
First dose of study intervention up to 4 years
Secondary outcome [7] 0 0
Double-blinded Part: Serum Concentration Observed Immediately at the End of Infusion (Ceoi) of Bintrafusp alfa
Timepoint [7] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [8] 0 0
Double-blinded Part: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa
Timepoint [8] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [9] 0 0
Safety Run-in Part: Area Under Serum Concentration-Time Curve (AUC0-t) From Time Zero to The Last Sampling Time of Bintrafusp alfa
Timepoint [9] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [10] 0 0
Safety Run-in Part: Area Under Serum Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp alfa
Timepoint [10] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [11] 0 0
Safety Run-in Part: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa
Timepoint [11] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [12] 0 0
Safety Run-in Part: Time to Reach Maximum Observed Serum Concentration (Tmax) of Bintrafusp alfa
Timepoint [12] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [13] 0 0
Safety Run-in Part: Apparent Terminal Half-Life (t1/2) of Bintrafusp alfa
Timepoint [13] 0 0
Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [14] 0 0
Double-blinded Part: Immunogenicity as measured by Anti-drug Antibodies Concentration
Timepoint [14] 0 0
Pre-dose, 30 minutes post-dose at Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years
Secondary outcome [15] 0 0
Double-blinded Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
Timepoint [15] 0 0
First dose of study intervention up to 4 years

Eligibility
Key inclusion criteria
- Are participants with histologically or cytologically confirmed locally advanced or
metastatic BTC

- Participants must have available tumor tissue (primary or metastatic) (archival or
fresh biopsies) before the first administration of study treatment

- At least 1 measurable lesion according to RECIST 1.1

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study
entry and at Week 1, Day 1 prior to dosing

- Life expectancy of >= 12 weeks, as judged by the Investigator

- Adequate hematological function, hepatic function, renal function, coagulation
function as defined in the protocol

- Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be
treated and on a stable dose of antivirals

- Other protocol defined inclusion criteria could apply
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous and/or intercurrent cancers

- Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
but with the exception of transplants that do not require immunosuppression

- Participants with symptomatic central nervous system (CNS) metastases

- Significant acute or chronic infection including known history of positive test for
human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary
infection and active bacterial or fungal infection requiring systemic therapy (with
the exception of hepatitis B and hepatitis C) requiring systemic therapy at study
entry and at Week 1 Day 1 prior to dosing.

- Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent

- History of or concurrent interstitial lung disease

- History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent
(within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
randomization

- Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune
checkpoints)

- Other protocol defined exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - PARENT - Blacktown
Recruitment hospital [2] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Epworth Freemasons - Melbourne
Recruitment postcode(s) [1] 0 0
- Blacktown
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Ciudad Autonoma Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
La Rioja
Country [10] 0 0
Argentina
State/province [10] 0 0
Salta
Country [11] 0 0
Argentina
State/province [11] 0 0
San Miguel de Tucuman
Country [12] 0 0
Argentina
State/province [12] 0 0
San Salvador de Jujuy
Country [13] 0 0
Brazil
State/province [13] 0 0
Rio Do Janeiro
Country [14] 0 0
Brazil
State/province [14] 0 0
Sao Paulo
Country [15] 0 0
Chile
State/province [15] 0 0
La Serena
Country [16] 0 0
Chile
State/province [16] 0 0
Santiago
Country [17] 0 0
Chile
State/province [17] 0 0
Temuco
Country [18] 0 0
France
State/province [18] 0 0
Angers Cedex 2
Country [19] 0 0
France
State/province [19] 0 0
Dijon cedex
Country [20] 0 0
France
State/province [20] 0 0
Lille cedex
Country [21] 0 0
France
State/province [21] 0 0
Saint Herblain
Country [22] 0 0
France
State/province [22] 0 0
Toulouse Cedex 9
Country [23] 0 0
Japan
State/province [23] 0 0
Aichi-Ken
Country [24] 0 0
Japan
State/province [24] 0 0
Chiba-Ken
Country [25] 0 0
Japan
State/province [25] 0 0
Fukuoka-Ken
Country [26] 0 0
Japan
State/province [26] 0 0
Kanagawa-Ken
Country [27] 0 0
Japan
State/province [27] 0 0
Osaka-Fu
Country [28] 0 0
Japan
State/province [28] 0 0
Tokyo-To
Country [29] 0 0
Japan
State/province [29] 0 0
Osaka-shi
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Gyeonggi-do
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Daejeon
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Poland
State/province [33] 0 0
Gliwice
Country [34] 0 0
Poland
State/province [34] 0 0
Krakow
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Poland
State/province [36] 0 0
Zamosc
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Caceres
Country [39] 0 0
Spain
State/province [39] 0 0
Cordoba
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Spain
State/province [41] 0 0
Valencia
Country [42] 0 0
Taiwan
State/province [42] 0 0
Kaohsiung
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taichung
Country [44] 0 0
Taiwan
State/province [44] 0 0
Tainan
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Study consists of an open-label, safety run-in part and a randomized, double-blind,
placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study will evaluate whether
bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus
cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve
participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and
cisplatin.
Trial website
https://clinicaltrials.gov/show/NCT04066491
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
eMediUSA@emdserono.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04066491