Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer (NCT NCT04349280)

Last Updated: 2024-04-18

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Up to approximately 22 months

Results posted on

2024-04-18

Participant Flow

Participant milestones

Participant milestones
Measure	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	PACT Phase - 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 approximately 56 weeks.
Main Study (Up to Approx. 95 Weeks) STARTED	25	0
Main Study (Up to Approx. 95 Weeks) COMPLETED	12	0
Main Study (Up to Approx. 95 Weeks) NOT COMPLETED	13	0
PACT Phase (Up to Approx. 56 Weeks) STARTED	0	1
PACT Phase (Up to Approx. 56 Weeks) COMPLETED	0	0
PACT Phase (Up to Approx. 56 Weeks) NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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	PACT Phase - 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 approximately 56 weeks.
Main Study (Up to Approx. 95 Weeks) Ongoing	1	0
Main Study (Up to Approx. 95 Weeks) Death	12	0
PACT Phase (Up to Approx. 56 Weeks) Adverse Event	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study - Bintrafusp Alfa n=25 Participants 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
Age, Continuous	67.3 Years STANDARD_DEVIATION 7.16 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 22 months

Population: Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.

Outcome measures

Outcome measures
Measure	Main Study - Bintrafusp Alfa n=25 Participants 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
Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	20.0 Percentage of Participants Interval 6.83 to 40.7

SECONDARY outcome

Timeframe: Up to approximately 22 months

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Main Study - Bintrafusp Alfa n=25 Participants 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
Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) Treatment Emergent AEs	25 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) Treatment Emergent SAEs	17 Participants

SECONDARY outcome

Timeframe: Up to approximately 22 months

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Main Study - Bintrafusp Alfa n=25 Participants 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
Number of Participants With Worst Grade Treatment Emergent AEs Grade 1	1 Participants
Number of Participants With Worst Grade Treatment Emergent AEs Grade 2	6 Participants
Number of Participants With Worst Grade Treatment Emergent AEs Grade 3	15 Participants
Number of Participants With Worst Grade Treatment Emergent AEs Grade 4	1 Participants
Number of Participants With Worst Grade Treatment Emergent AEs Grade 5	2 Participants

Adverse Events

Main Study - Bintrafusp Alfa

Serious events: 17 serious events

Other events: 21 other events

Deaths: 12 deaths

PACT Phase - Bintrafusp Alfa

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Main Study - Bintrafusp Alfa n=25 participants at risk 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	PACT Phase - Bintrafusp Alfa n=1 participants at risk 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 approximately 56 weeks.
Blood and lymphatic system disorders Anaemia	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Gastrointestinal disorders Colitis	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
General disorders General physical health deterioration	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
General disorders Mucosal inflammation	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
General disorders Pyrexia	8.0% 2/25 • Number of events 3 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Infections and infestations COVID-19 pneumonia	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Infections and infestations Pseudomonal sepsis	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Infections and infestations Sepsis	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Infections and infestations Septic shock	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Infections and infestations Urinary tract infection	16.0% 4/25 • Number of events 4 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Investigations Blood creatinine increased	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Nervous system disorders Haemorrhage intracranial	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Psychiatric disorders Delirium	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Renal and urinary disorders Acute kidney injury	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	100.0% 1/1 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Renal and urinary disorders Nephropathy	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	4.0% 1/25 • Number of events 1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.	0.00% 0/1 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 95 weeks for main study and up to approximately 56 weeks for PACT phase. Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.