Neoplasms
Conditions
Keywords
Bintrafusp Alfa, Platinum Agent, Response Evaluation Criteria in Solid Tumors, Urothelial Cancer, M7824
Brief summary
The purpose of this study is to evaluate bintrafusp alfa in participants with metastatic or locally advanced urothelial cancer. This trial provides the first evaluation of bintrafusp alfa in participants with urothelial cancer that has progressed following platinum therapy.
Interventions
DRUGBintrafusp alfa
Participants will receive bintrafusp alfa.
Sponsors
Merck KGaA, Darmstadt, Germany
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open label study.
Intervention model description
This is a single arm study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants can give signed informed consent/assent. * Participants with histologically confirmed locally advanced or metastatic or locally advanced/unresectable urothelial carcinoma (including renal, pelvis, ureter, urinary bladder, urethra). * Able to provide, a tumor tissue sample collected during screening and prior to administration of bintrafusp alfa. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * Participants with adequate organ system functions. * Life expectancy of at least 12 weeks. * A female is eligible if she is not pregnant or breastfeeding.
Exclusion criteria
* Active brain and/or leptomeningeal disease that is symptomatic or requires therapeutic intervention. Participants with asymptomatic central nervous system (CNS) metastases who are clinically stable as demonstrated by serial brain images and have no requirement for corticosteroids for at least 14 days prior to enrollment are eligible. * History of malignancy other than urothelial cancer within the last 3 years except for localized tumors that have been treated with curative intent or have not required therapy in the past 2 years. (e.g., resected non-melanoma skin cancer). * No more than 2 lines of systemic therapy for the treatment of metastastic disease. If the most recent therapy was not a platinum-based regimen, the participant must have progressed on or after that therapy. * Cirrhosis or current unstable liver or biliary disease per investigator assessment. * Current pneumonitis or history of non-infectious pneumonitis that required systemic immunosuppressive treatment. * Active autoimmune disease that required systemic immunosuppressive treatment within the past 2 years. * Received prior allogeneic/autologous bone marrow or solid organ transplant. * Receiving systemic corticosteroids (\>10 milligrams \[mg\] daily oral prednisone or equivalent) or other immunosuppressive agent within 7 days prior to study treatment. Inhaled or topical steroids are permitted. * Known severe hypersensitivity reactions to monoclonal antibodies or any ingredient used in the study treatment formulation (Grade \>=3 National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0). * Active infection requiring systemic therapy. * Received any live vaccine within 30 days prior first dose of intervention. * Known history of positive test for human immunodeficiency virus (HIV) with the exception of participants with cluster of differentiation 4 (CD4) + T-cell (CD4+) counts \>=350 cells per microliter (cells /uL) and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections. * Active hepatitis B virus (HBV) (HBV surface antigen-positive). * Active hepatitis C virus (HCV) infection, or positive HCV antibody, with the exception of participants that 1. Have HCV viral load below the limits of quantitation and 2. Completed curative antiviral therapy or are receiving and compliant with antiviral therapy. * History or evidence of cardiac abnormalities within the 6 months prior to first dose of intervention. * Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded. * Any other serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results. * Received prior systemic anti-cancer therapy within 2 weeks prior to study treatment. * Received prior therapy with an anti-programmed death 1 (PD-1), anti-programmed death Ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). * Received prior therapy targeting transforming growth factor (TGF) beta - (e.g., Galunistertib). * Received radiation therapy (or other non-systemic disease therapy) within 2 weeks prior to study treatment. * Undergone major surgery within 4 weeks prior to administration of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to approximately 22 months | Confirmed overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) | Up to approximately 22 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent. |
| Number of Participants With Worst Grade Treatment Emergent AEs | Up to approximately 22 months | Treatment emergent adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent. |
Countries
Canada, France, Netherlands, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Main Study - Bintrafusp Alfa Participants with metastatic or locally advanced/unresectable urothelial cancer with disease progression or recurrence received intravenous (IV) infusion of 1200 milligram (mg) of bintrafusp alfa over 1 hour once every 2 weeks up to 79 weeks | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Main Study (Up to Approx. 95 Weeks) | Death | 12 | 0 |
| Main Study (Up to Approx. 95 Weeks) | Ongoing | 1 | 0 |
| PACT Phase (Up to Approx. 56 Weeks) | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Main Study - Bintrafusp Alfa |
|---|---|
| Age, Continuous | 67.3 Years STANDARD_DEVIATION 7.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 25 | 0 / 1 |
| other Total, other adverse events | 21 / 25 | 0 / 1 |
| serious Total, serious adverse events | 17 / 25 | 1 / 1 |
Outcome results
Primary
Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Confirmed overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).
Time frame: Up to approximately 22 months
Population: Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study - Bintrafusp Alfa | Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 20.0 Percentage of Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.
Time frame: Up to approximately 22 months
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study - Bintrafusp Alfa | Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment Emergent AEs | 25 Participants |
| Main Study - Bintrafusp Alfa | Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment Emergent SAEs | 17 Participants |
Secondary
Number of Participants With Worst Grade Treatment Emergent AEs
Treatment emergent adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.
Time frame: Up to approximately 22 months
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study - Bintrafusp Alfa | Number of Participants With Worst Grade Treatment Emergent AEs | Grade 1 | 1 Participants |
| Main Study - Bintrafusp Alfa | Number of Participants With Worst Grade Treatment Emergent AEs | Grade 2 | 6 Participants |
| Main Study - Bintrafusp Alfa | Number of Participants With Worst Grade Treatment Emergent AEs | Grade 3 | 15 Participants |
| Main Study - Bintrafusp Alfa | Number of Participants With Worst Grade Treatment Emergent AEs | Grade 4 | 1 Participants |
| Main Study - Bintrafusp Alfa | Number of Participants With Worst Grade Treatment Emergent AEs | Grade 5 | 2 Participants |