Solid TumorsPhase 1NCT02699515

MSB0011359C (M7824) in Participants With Metastatic or Locally Advanced Solid Tumors

A Phase 1 study testing MSB0011359C in people with Solid Tumors, run by Merck KGaA, Darmstadt, Germany at 18 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The main purpose of this study was to assess the safety and tolerability of MSB0011359C. Study consists of dose-escalation part and an expansion part in participants with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or a standard therapy had failed. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Solid Tumors
What is being tested?: MSB0011359C
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 114 participants
Where: 18 sitesin 3 countries
Study dates: 11 Mar 2016to 21 Feb 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Able and willing to give written informed consent and had signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
Eligible male and female participants aged greater than or equal to (>=)20 years
Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no effective standard therapy exists or standard therapy had failed
Eastern Cooperative Oncology Group performance status (ECOG) performance status of 0 to 1 at trial entry
Life expectancy >=12 weeks as judged by the Investigator.
Adequate hematological function defined by white blood cell (WBC) count >=3*10^9/Liter with absolute neutrophil count (ANC) >=1.5*10^9/Liter, lymphocyte count >=0.5* 10^9/Liter, platelet count >=75*10^9/Liter, and Hemoglobin (Hgb) >= 9 grams per deciliter (g/dL) (in absence of blood transfusion)

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Adequate hepatic function defined by a total bilirubin level <=1.5 × Upper limit of normal (ULN), an AST level <= 2.5 × ULN, and an ALT level <= 2.5 × ULN
Adequate renal function defined by an estimated creatinine clearance >50 milliliter per minute (mL/min) according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24 hour urine collection
Other protocol-defined exclusion criteria could apply.

Who cannot join

Concurrent treatment with non-permitted drugs and other interventions
Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy
Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy)
Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
Previous malignant disease other than the target malignancy to be investigated in this trial with the exception of cervical carcinoma in situ and superficial or non invasive bladder cancer (treated with curative intent) within the last 5 years or basal cell or squamous cell carcinoma in situ within the last 3 years
Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
Active or history of central nervous system metastases, except as in the melanoma-specific Central nervous system (CNS) criteria listed above
Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant)

Trial locations and contacts

18 sites in 3 countries.

Country

City, postcode or hospital

18 sites in 3 countries

Japan11 sites

NHO Kyushu Cancer Center
Fukuoka
National Cancer Center East, Department of Experimental Therapeutics
Kashiwa
National Cancer Center East, Department of hepatobiliary and pancreatic oncology
Kashiwa
Saitama Cancer Center
Kitaadachi-gun
NHO Shikoku Cancer Center
Matsuyama
Aichi Cancer Center Hospital
Nagoya
Kinki University Hospital
Sayama
National Cancer Center, Department of Experimental Therapeutics
Tokyo
National Cancer Center, Department of hepatobiliary and pancreatic oncology
Tokyo
Kanagawa Cancer Center, Department of Gastroenterology
Yokohama
Kanagawa Cancer Center, Department of Gastrointestinal Surgery
Yokohama

Other trials in Japan

Taiwan4 sites

National Cheng Kung University Hospital
Tainan
Mackay Memorial Hospital
Taipei
National Taiwan University Hospital
Taipei
Chang Gung Memorial Hospital; Linkou
Taoyuan

Other trials in Taiwan

South Korea3 sites

Asan Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital
Seoul

Other trials in South Korea

About this study

Official title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia

Conditions: Solid Tumors
Being tested: MSB0011359C
Keywords: MSB0011359C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MSB0011359CDrug
Also called M7824
Subjects with metastatic or locally advanced solid tumors received intravenous infusion of MSB0011359C over 1 hour once every two weeks for up to 12 months until confirmed progressive disease (PD), unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.

Study groups in NCT02699515
Study group	Role	What they receive
MSB0011359C (M7824)	Experimental	Not described Receives: Drug: MSB0011359C

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicity (DLT)
A DLT was defined as any grade greater than or equal to (>=) 3 adverse event suspected to be related to investigational medicinal product (IMP) by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment.
Measured: Baseline up to Week 3
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Measured: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years
Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
Measured: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years

Secondary outcomes (12)

Dose-Escalation Phase: Maximum Serum Concentration (Cmax) of M7824
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Measured: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Dose-Escalation Phase: Terminal Half Life (t1/2) of M7824
t1/2 was the time measured for the concentration to decrease by one half, determined as 0.693/Lambda z, here Lambda z was the terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Measured: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Dose-Escalation Phase: Area Under the Serum Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of M7824
Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated by linear trapezoidal summation.
Measured: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43
Dose-Escalation Phase: Area Under The Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M7824
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Measured: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43
Dose-Escalation Phase: Number of Participants With Positive Serum Titers of Anti-Drug Antibodies of M7824
The detection of antibodies to M7824 was performed using a validated electrochemiluminescence (ECL) immunoassay with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of M7824 were reported.
Measured: Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years
Dose-Escalation Part: Number of Participants With Best Overall Response (BOR) As Assessed By Investigator
BOR was assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. BOR was defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.
Measured: Date of randomization up to 2 years
Expansion Part: Best Overall Response (BOR) As Assessed By Investigator
BOR was assessed by investigator according to RECIST Version 1.1. BOR was defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD.
Measured: Date of randomization up to 2 years
Expansion Part: BOR According to RECIST 1.1 As Adjudicated By The Independent Review Committee (IRC)
The BOR per Independent Endpoint Review Committee (IRC) adjudication was determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD.
Measured: Up to 2 years
Expansion Part: Duration of Response (DOR)
Duration of response according to RECIST 1.1 as adjudicated by the IRC was defined as the time from first confirmed response until the first documented disease progression that was subsequently confirmed. It was analyzed using Kaplan-Meier method.
Measured: Up to 2 years
Expansion Part: Disease Control Rate
The disease control rate was defined as the percentage of participants with BOR. The BOR per IRC adjudication was determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD.
Measured: Up to 2 years
Expansion Part: Progression Free Survival (PFS) Time
PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as RECIST v1.1 as adjudicated by IRC. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Measured: Date of randomization until death or progressive disease assessed up to 2 years
Expansion Part: Overall Survival (OS) Time
OS was defined as the time from randomization to death due to any cause.
Measured: Date of randomization until death assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Mar 201621 Feb 2022

First posted4 Mar 2016 (estimated)
Study start11 Mar 2016
Primary completion21 Feb 2022
Study completion21 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02699515
Sponsor's protocol ID: 200647-0008
Status last verified: Sep 2024
First submitted: 1 Mar 2016
Last updated: 18 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Lin CC, Doi T, Muro K, Hou MM, Esaki T, Hara H, Chung HC, Helwig C, Dussault I, Osada M, Kondo S. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFbeta and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia. Target Oncol. 2021 Jul;16(4):447-459. doi: 10.1007/s11523-021-00810-9. Epub 2021 Apr 11.
PubMed 33840050
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.
PubMed 32461347
Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.
PubMed 36066618
Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.
PubMed 31278692

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia
ClinicalTrials.gov ID: NCT02699515
Acronym / sponsor ID: 200647-0008
Conditions: Solid Tumors
Keywords: MSB0011359C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 114 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 11 Mar 2016 (actual)
Primary completion: 21 Feb 2022 (actual)
Study completion: 21 Feb 2022 (actual)
First posted: 4 Mar 2016 (estimated)
Results: Posted 18 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
MSB0011359C (M7824)	Experimental	Drug: MSB0011359C

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Able and willing to give written informed consent and had signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
Eligible male and female participants aged greater than or equal to (>=)20 years
Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no effective standard therapy exists or standard therapy had failed
Eastern Cooperative Oncology Group performance status (ECOG) performance status of 0 to 1 at trial entry
Life expectancy >=12 weeks as judged by the Investigator.

Key exclusion criteria (8 listed)

Concurrent treatment with non-permitted drugs and other interventions
Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy
Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy)
Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
Previous malignant disease other than the target malignancy to be investigated in this trial with the exception of cervical carcinoma in situ and superficial or non invasive bladder cancer (treated with curative intent) within the last 5 years or basal cell or squamous cell carcinoma in situ within the last 3 years

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MSB0011359CAlso: M7824Subjects with metastatic or locally advanced solid tumors received intravenous infusion of MSB0011359C over 1 hour once every two weeks for up to 12 months until confirmed progressive disease (PD), unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.	Drug	MSB0011359C (M7824)

Primary outcome

Number of Participants With Dose Limiting Toxicity (DLT)
Time frame: Baseline up to Week 3
A DLT was defined as any grade greater than or equal to (>=) 3 adverse event suspected to be related to investigational medicinal product (IMP) by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03
Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03
Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

12 secondary outcomes

Dose-Escalation Phase: Maximum Serum Concentration (Cmax) of M7824
Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Dose-Escalation Phase: Terminal Half Life (t1/2) of M7824
Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Dose-Escalation Phase: Area Under the Serum Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of M7824
Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43
Dose-Escalation Phase: Area Under The Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M7824
Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43
Dose-Escalation Phase: Number of Participants With Positive Serum Titers of Anti-Drug Antibodies of M7824
Time frame: Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years
Dose-Escalation Part: Number of Participants With Best Overall Response (BOR) As Assessed By Investigator
Time frame: Date of randomization up to 2 years
Expansion Part: Best Overall Response (BOR) As Assessed By Investigator
Time frame: Date of randomization up to 2 years
Expansion Part: BOR According to RECIST 1.1 As Adjudicated By The Independent Review Committee (IRC)
Time frame: Up to 2 years
Expansion Part: Duration of Response (DOR)
Time frame: Up to 2 years
Expansion Part: Disease Control Rate
Time frame: Up to 2 years
Expansion Part: Progression Free Survival (PFS) Time
Time frame: Date of randomization until death or progressive disease assessed up to 2 years
Expansion Part: Overall Survival (OS) Time
Time frame: Date of randomization until death assessed up to 2 years

Results and safety

Results posted to the registry on 18 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Escalation Cohort: M7824 (3 mg/kg)	4	0
Dose Escalation Cohort: M7824 (10 mg/kg)	3	0
Dose Escalation Cohort: M7824 (20 mg/kg)	7	0
Expansion Cohort: Biliary Tract Cancer	30	0
Expansion Cohort: Gastric Cancer (GC)	31	0
Expansion Cohort: Esophageal Squamous Cell Cancer	30	1
Expansion Cohort: Hepatocellular Carcinoma (3 mg/kg)	3	0
Expansion Cohort: Hepatocellular Carcinoma (10 mg/kg)	6	0

Primary outcome: Number of Participants With Dose Limiting Toxicity (DLT)

Time frame: Baseline up to Week 3. Count of participants. Unit: Participants

Measure	Dose Escalation Cohort: M7824 (3 mg/kg) n = 4	Dose Escalation Cohort: M7824 (10 mg/kg) n = 3	Dose Escalation Cohort: M7824 (20 mg/kg) n = 6
Value	0	0	1

Population analysed: DLT analysis set included all participants with data used for implementing the dose-escalation schedule. These participants received all study treatment administrations in the DLT evaluation period or stopped treatment because of DLTs in the DLT evaluation period.

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03

Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years. Count of participants. Unit: Participants

Measure	Dose Escalation Cohort: M7824 (3 mg/kg) n = 4	Dose Escalation Cohort: M7824 (10 mg/kg) n = 3	Dose Escalation Cohort: M7824 (20 mg/kg) n = 7	Expansion Cohort: Biliary Tract Cancer n = 30	Expansion Cohort: Gastric Cancer (GC) n = 31	Expansion Cohort: Esophageal Squamous Cell Cancer n = 30	Expansion Cohort: Hepatocellular Carcinoma (3 mg/kg) n = 3	Expansion Cohort: Hepatocellular Carcinoma (10 mg/kg) n = 6
Value	4	3	6	28	30	30	2	6

Population analysed: Safety Analysis Set (SAF) included all participants who received at least 1 dose of study treatment.

Primary outcome: Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03

Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years. Count of participants. Unit: Participants

Measure	Dose Escalation Cohort: M7824 (3 mg/kg) n = 4	Dose Escalation Cohort: M7824 (10 mg/kg) n = 3	Dose Escalation Cohort: M7824 (20 mg/kg) n = 7	Expansion Cohort: Biliary Tract Cancer n = 30	Expansion Cohort: Gastric Cancer (GC) n = 31	Expansion Cohort: Esophageal Squamous Cell Cancer n = 30	Expansion Cohort: Hepatocellular Carcinoma (3 mg/kg) n = 3	Expansion Cohort: Hepatocellular Carcinoma (10 mg/kg) n = 6
Value	1	2	3	19	16	19	0	0

Population analysed: Safety analysis set included all participants who received at least 1 dose of study treatment.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately up to 5 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Expansion Cohort: Biliary Tract Cancer	18 of 30 (60%)	28 of 30 (93.3%)	23 of 30
Expansion Cohort: Gastric Cancer (GC)	18 of 31 (58.1%)	30 of 31 (96.8%)	22 of 31
Expansion Cohort: Esophageal Squamous Cell Cancer	14 of 30 (46.7%)	30 of 30 (100%)	24 of 30
Dose Escalation Cohort: M7824 (3 mg/kg)	4 of 4 (100%)	4 of 4 (100%)	3 of 4
Dose Escalation Cohort: M7824 (10 mg/kg)	0 of 3 (0%)	3 of 3 (100%)	3 of 3
Dose Escalation Cohort: M7824 (20 mg/kg)	5 of 7 (71.4%)	6 of 7 (85.7%)	3 of 7
Expansion Cohort: Hepatocellular Carcinoma (3 mg/kg)	2 of 3 (66.7%)	1 of 3 (33.3%)	3 of 3
Expansion Cohort: Hepatocellular Carcinoma (10 mg/kg)	3 of 6 (50%)	6 of 6 (100%)	5 of 6

Limitations and caveats (from the sponsor): Data collection and analysis of Pharmacokinetics of Cmin was omitted and not conducted due to business reason.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 33840050Lin CC, Doi T, Muro K, Hou MM, Esaki T, Hara H, Chung HC, Helwig C, Dussault I, Osada M, Kondo S. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFbeta and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia. Target Oncol. 2021 Jul;16(4):447-459. doi: 10.1007/s11523-021-00810-9. Epub 2021 Apr 11.
Results publication: PubMed 32461347Yoo 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.
Derived from this study: PubMed 36066618Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.
Derived from this study: PubMed 31278692Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.
INTR@PID Clinical Trial ProgramLink provided by the sponsor.
Trial Awareness and Transparency websiteLink provided by the sponsor.
Medical Information Location Map - Med Info ContactsLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck KGaA, Darmstadt, Germany

18 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MSB0011359C in people with Solid Tumors, run by Merck KGaA, Darmstadt, Germany at 18 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Japan, Taiwan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicity (DLT) (time frame: Baseline up to Week 3). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02699515, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.