Trial Outcomes & Findings for A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma (NCT NCT04501094)

Last Updated: 2022-03-22

Results Overview

The proportion of evaluable patients with objective response rate (ORR) defined as a partial response (PR) or complete response (CR) at the end of treatment with Bintrafusp alfa (M7824). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, approximately 3 months.

Results posted on

2022-03-22

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Overall Study STARTED	1	1
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Overall Study Death (unrelated to research)	1	0

Baseline Characteristics

A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, approximately 3 months.

Outcome measures

Outcome measures
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Proportion of Participants With an Objective Response Rate (ORR) Partial Response	0 Proportion of participants	0 Proportion of participants
Proportion of Participants With an Objective Response Rate (ORR) Complete Response	0 Proportion of participants	0 Proportion of participants

SECONDARY outcome

Timeframe: Until confirmed progression, unacceptable toxicity or trial withdrawal, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.

The number of participants with toxicity grade \>1 assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse events.

Outcome measures

Outcome measures
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Number of Participants With Toxicity Grade >1 Grade 5	0 Participants	0 Participants
Number of Participants With Toxicity Grade >1 Grade 1	1 Participants	1 Participants
Number of Participants With Toxicity Grade >1 Grade 2	1 Participants	1 Participants
Number of Participants With Toxicity Grade >1 Grade 3	1 Participants	1 Participants
Number of Participants With Toxicity Grade >1 Grade 4	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, approximately 6 weeks (first scheduled restaging scan)

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study; and the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Number of Participants With Progression Free Survival (PFS)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Time from treatment to the date of death from any cause, approximately 11 months.

Here is the number of participants that survived.

Outcome measures

Outcome measures
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Number of Participants That Survived	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	1 Participants	1 Participants

Adverse Events

Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 participants at risk Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 participants at risk Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death from progressive	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
General disorders Pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.

Other adverse events

Additional Information

Dr. Andrea B. Apolo

National Cancer Institute

Phone: 301-480-0536

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 Participants Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Total n=2 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 0 • n=5 Participants	71.5 years STANDARD_DEVIATION 0 • n=7 Participants	66.4 years STANDARD_DEVIATION 7.21 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants

Measure	Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy n=1 participants at risk Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks	Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease n=1 participants at risk Treatment with Bintrafusp alfa (M7824) Bintrafusp alfa (M7824): 1200 mg administered intravenous (IV) every two weeks
Blood and lymphatic system disorders Anemia	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Infections and infestations Bacteremia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Injury, poisoning and procedural complications Bruising	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Gastrointestinal disorders Diarrhea	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
General disorders Fatigue	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Nervous system disorders Headache	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Vascular disorders Hypertension	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Metabolism and nutrition disorders Hyponatremia	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Vascular disorders Hypotension	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Investigations Lipase increased	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Investigations Lymphocyte count decreased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Gastrointestinal disorders Oral hemorrhage	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
General disorders Pain	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.
Skin and subcutaneous tissue disorders Skin ulceration	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.