Trial Outcomes & Findings for Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer (NCT NCT04246489)

Last Updated: 2023-10-23

Results Overview

Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

146 participants

Primary outcome timeframe

Time from first treatment up to 688 days

Results posted on

2023-10-23

Participant Flow

A total of 203 participants were screened, of which 146 participants received bintrafusp alfa monotherapy.

Participant milestones

Participant milestones
Measure	Bintrafusp Alfa Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Overall Study STARTED	146
Overall Study COMPLETED	146
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Age, Continuous	52 Years STANDARD_DEVIATION 12.5 • n=39 Participants
Sex: Female, Male Female	146 Participants n=39 Participants
Sex: Female, Male Male	0 Participants n=39 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=39 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants n=39 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants
Race (NIH/OMB) Asian	90 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=39 Participants
Race (NIH/OMB) Black or African American	1 Participants n=39 Participants
Race (NIH/OMB) White	37 Participants n=39 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=39 Participants

PRIMARY outcome

Timeframe: Time from first treatment up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	32 Participants

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

DOR was defined for participants with confirmed response, as the time from first documentation of confirmed objective response (Complete Response \[CR\] or Partial Response \[PR\]) according to RECIST 1.1 to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	NA months Interval 7.4 to The median was not reached, and the upper limit could not be estimated due to insufficient number of events

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

Durable Response was defined as the number of participants with confirmed objective response (CR or PR) according to RECIST 1.1, determined by IRC with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	19 Participants

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: Safety analysis set included all participants who were administered at least one dose of bintrafusp alfa

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions, Immune-related AEs, Transforming growth factor- beta (TGF-ß) inhibition mediated skin AE, bleeding and anemia.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) TEAE's	145 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) Treatment Related TEAEs	106 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Infusion-related reaction	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Immune-related AE	49 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: TGF-beta inhibition mediated skin AE	7 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Anemia	82 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Bleeding events	81 Participants

SECONDARY outcome

Timeframe: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

PFS was defined as the time from first administration of study intervention until date of the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Kaplan-Meier estimates was used to calculate PFS.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	1.9 months Interval 1.8 to 2.2

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator	25 Participants

SECONDARY outcome

Timeframe: Time from first administration of study drug up to data cutoff (assessed up to 688 days)

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.

OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=146 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Overall Survival (OS)	13.7 months Interval 10.6 to 17.1

SECONDARY outcome

Timeframe: At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505 and Day 589

Population: Pharmacokinetic (PK) analysis set included all participants who completed at least one dose of bintrafusp alfa and who provided at least one sample with a measurable concentration of bintrafusp alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points for this outcome measure.

Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing).

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=143 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 15	73.7 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 55.3
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 29	107 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 48.7
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 43	108 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 53
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 85	115 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 44.9
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 127	107 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 69
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 169	137 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 41
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 253	101 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 45.8
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 337	120 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 50.9
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 421	103 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 56.4
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 505	220 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 22.4
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa Day 589	154 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 10.4

SECONDARY outcome

Timeframe: At Day 1 and Day 29

Population: PK analysis set included all participants who completed at least one dose of Bintrafusp Alfa and who provided at least one sample with a measurable concentration of Bintrafusp Alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points for this outcome measure.

Serum Concentration at End of Infusion (CEOI) of bintrafusp alfa is reported.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=143 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa Day 1	469 mcg/mL Geometric Coefficient of Variation 21.9
Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa Day 29	546 mcg/mL Geometric Coefficient of Variation 24.1

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: Immunogenicity analysis set included all participants who received at least one dose of bintrafusp alfa and who had at least one valid result of ADA.

Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=142 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Number of Participants With Positive Antidrug Antibodies (ADA)	33 Participants

SECONDARY outcome

Timeframe: Time from first treatment up to 688 days

Population: FAS included all participants who were administered at least one dose of bintrafusp alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified categories for this outcome measure.

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=141 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 positive tumors (CPS>=1)	25.6 percentage of participants Interval 16.8 to 36.1
Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 negative tumors (CPS <1)	18.2 percentage of participants Interval 9.1 to 30.9

SECONDARY outcome

Timeframe: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days

PFS was defined as the time from first administration of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=141 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
PFS According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 positive tumors (CPS>=1)	1.9 months Interval 1.8 to 4.3
PFS According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 negative tumors (CPS<1)	1.9 months Interval 1.7 to 2.0

SECONDARY outcome

Timeframe: Time from first administration of study drug up to 688 days

OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

Outcome measures

Outcome measures
Measure	Bintrafusp Alfa n=141 Participants Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 positive tumors (CPS>=1)	17.5 months Interval 12.5 to Due to small number of events Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derived.
Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 negative tumors (CPS<1)	8.7 months Interval 5.8 to 11.8

Adverse Events

Bintrafusp Alfa

Serious events: 94 serious events

Other events: 139 other events

Deaths: 76 deaths

Serious adverse events

Serious adverse events
Measure	Bintrafusp Alfa n=146 participants at risk Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Blood and lymphatic system disorders Anaemia	9.6% 14/146 • Time from first treatment up to 688 days
Blood and lymphatic system disorders Blood loss anaemia	0.68% 1/146 • Time from first treatment up to 688 days
Blood and lymphatic system disorders Febrile neutropenia	1.4% 2/146 • Time from first treatment up to 688 days
Cardiac disorders Cardiac failure	0.68% 1/146 • Time from first treatment up to 688 days
Endocrine disorders Adrenal insufficiency	1.4% 2/146 • Time from first treatment up to 688 days
Endocrine disorders Immune-mediated thyroiditis	0.68% 1/146 • Time from first treatment up to 688 days
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.68% 1/146 • Time from first treatment up to 688 days
Endocrine disorders Secondary adrenocortical insufficiency	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Abdominal pain	1.4% 2/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Anal haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Colitis	2.7% 4/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Dental caries	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Gastric haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Gastric ulcer haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Ileus	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Malignant gastrointestinal obstruction	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Mouth ulceration	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Obstructive defaecation	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Pancreatitis	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Pancreatitis acute	1.4% 2/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Rectal haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Subileus	0.68% 1/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Vomiting	0.68% 1/146 • Time from first treatment up to 688 days
General disorders Asthenia	1.4% 2/146 • Time from first treatment up to 688 days
General disorders Disease progression	8.2% 12/146 • Time from first treatment up to 688 days
General disorders General physical health deterioration	2.7% 4/146 • Time from first treatment up to 688 days
General disorders Malaise	0.68% 1/146 • Time from first treatment up to 688 days
General disorders Pain	0.68% 1/146 • Time from first treatment up to 688 days
Hepatobiliary disorders Cholangitis acute	0.68% 1/146 • Time from first treatment up to 688 days
Hepatobiliary disorders Drug-induced liver injury	0.68% 1/146 • Time from first treatment up to 688 days
Hepatobiliary disorders Hepatic function abnormal	1.4% 2/146 • Time from first treatment up to 688 days
Hepatobiliary disorders Hepatic pain	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Abdominal sepsis	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Brain abscess	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Intestinal fistula infection	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Kidney infection	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Lung abscess	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Pyelonephritis	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Pyelonephritis acute	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Sepsis	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Septic arthritis streptococcal	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Urinary tract infection	1.4% 2/146 • Time from first treatment up to 688 days
Infections and infestations Urinary tract infection bacterial	0.68% 1/146 • Time from first treatment up to 688 days
Infections and infestations Urosepsis	0.68% 1/146 • Time from first treatment up to 688 days
Injury, poisoning and procedural complications Cystitis radiation	1.4% 2/146 • Time from first treatment up to 688 days
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.68% 1/146 • Time from first treatment up to 688 days
Injury, poisoning and procedural complications Radiation proctitis	0.68% 1/146 • Time from first treatment up to 688 days
Injury, poisoning and procedural complications Spinal compression fracture	0.68% 1/146 • Time from first treatment up to 688 days
Injury, poisoning and procedural complications Stoma obstruction	0.68% 1/146 • Time from first treatment up to 688 days
Investigations Amylase increased	0.68% 1/146 • Time from first treatment up to 688 days
Investigations Lipase increased	0.68% 1/146 • Time from first treatment up to 688 days
Investigations Transaminases increased	0.68% 1/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Decreased appetite	0.68% 1/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Diabetic ketoacidosis	1.4% 2/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Malnutrition	0.68% 1/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.68% 1/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Arthralgia	0.68% 1/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Back pain	0.68% 1/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Myositis	0.68% 1/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Pathological fracture	1.4% 2/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.68% 1/146 • Time from first treatment up to 688 days
Nervous system disorders Altered state of consciousness	1.4% 2/146 • Time from first treatment up to 688 days
Nervous system disorders Brain oedema	0.68% 1/146 • Time from first treatment up to 688 days
Nervous system disorders Embolic stroke	0.68% 1/146 • Time from first treatment up to 688 days
Nervous system disorders Myasthenia gravis	0.68% 1/146 • Time from first treatment up to 688 days
Nervous system disorders Neuritis	0.68% 1/146 • Time from first treatment up to 688 days
Nervous system disorders Polyneuropathy in malignant disease	0.68% 1/146 • Time from first treatment up to 688 days
Product Issues Device dislocation	1.4% 2/146 • Time from first treatment up to 688 days
Renal and urinary disorders Acute kidney injury	2.1% 3/146 • Time from first treatment up to 688 days
Renal and urinary disorders Cystitis haemorrhagic	1.4% 2/146 • Time from first treatment up to 688 days
Renal and urinary disorders Haematuria	10.3% 15/146 • Time from first treatment up to 688 days
Renal and urinary disorders Haemorrhage urinary tract	0.68% 1/146 • Time from first treatment up to 688 days
Renal and urinary disorders Hydronephrosis	2.1% 3/146 • Time from first treatment up to 688 days
Renal and urinary disorders Renal failure	1.4% 2/146 • Time from first treatment up to 688 days
Renal and urinary disorders Ureteral polyp	0.68% 1/146 • Time from first treatment up to 688 days
Renal and urinary disorders Urinary bladder haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Renal and urinary disorders Urinary retention	1.4% 2/146 • Time from first treatment up to 688 days
Reproductive system and breast disorders Female genital tract fistula	0.68% 1/146 • Time from first treatment up to 688 days
Reproductive system and breast disorders Genital haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Reproductive system and breast disorders Intermenstrual bleeding	1.4% 2/146 • Time from first treatment up to 688 days
Reproductive system and breast disorders Vaginal haemorrhage	0.68% 1/146 • Time from first treatment up to 688 days
Respiratory, thoracic and mediastinal disorders Asphyxia	0.68% 1/146 • Time from first treatment up to 688 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 2/146 • Time from first treatment up to 688 days
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.7% 4/146 • Time from first treatment up to 688 days
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.68% 1/146 • Time from first treatment up to 688 days
Skin and subcutaneous tissue disorders Erythema multiforme	0.68% 1/146 • Time from first treatment up to 688 days
Skin and subcutaneous tissue disorders Immune-mediated dermatitis	1.4% 2/146 • Time from first treatment up to 688 days
Vascular disorders Deep vein thrombosis	0.68% 1/146 • Time from first treatment up to 688 days
Vascular disorders Haematoma	0.68% 1/146 • Time from first treatment up to 688 days
Vascular disorders Hypovolaemic shock	0.68% 1/146 • Time from first treatment up to 688 days
Vascular disorders Venous thrombosis limb	0.68% 1/146 • Time from first treatment up to 688 days

Other adverse events

Other adverse events
Measure	Bintrafusp Alfa n=146 participants at risk Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Blood and lymphatic system disorders Anaemia	54.8% 80/146 • Time from first treatment up to 688 days
Endocrine disorders Hyperthyroidism	6.8% 10/146 • Time from first treatment up to 688 days
Endocrine disorders Hypothyroidism	11.6% 17/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Abdominal pain	8.2% 12/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Constipation	15.1% 22/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Diarrhoea	8.2% 12/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Gingival bleeding	11.6% 17/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Nausea	20.5% 30/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Stomatitis	6.8% 10/146 • Time from first treatment up to 688 days
Gastrointestinal disorders Vomiting	13.7% 20/146 • Time from first treatment up to 688 days
General disorders Asthenia	15.8% 23/146 • Time from first treatment up to 688 days
General disorders Oedema peripheral	8.2% 12/146 • Time from first treatment up to 688 days
General disorders Pyrexia	17.1% 25/146 • Time from first treatment up to 688 days
Infections and infestations Urinary tract infection	9.6% 14/146 • Time from first treatment up to 688 days
Investigations Alanine aminotransferase increased	13.7% 20/146 • Time from first treatment up to 688 days
Investigations Amylase increased	5.5% 8/146 • Time from first treatment up to 688 days
Investigations Aspartate aminotransferase increased	13.0% 19/146 • Time from first treatment up to 688 days
Investigations Blood alkaline phosphatase increased	6.8% 10/146 • Time from first treatment up to 688 days
Investigations Blood creatinine increased	6.2% 9/146 • Time from first treatment up to 688 days
Investigations Lipase increased	6.8% 10/146 • Time from first treatment up to 688 days
Investigations Weight decreased	5.5% 8/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Decreased appetite	16.4% 24/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Hypoalbuminaemia	10.3% 15/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Hypokalaemia	8.2% 12/146 • Time from first treatment up to 688 days
Metabolism and nutrition disorders Hyponatraemia	5.5% 8/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Arthralgia	5.5% 8/146 • Time from first treatment up to 688 days
Musculoskeletal and connective tissue disorders Back pain	6.8% 10/146 • Time from first treatment up to 688 days
Nervous system disorders Headache	7.5% 11/146 • Time from first treatment up to 688 days
Psychiatric disorders Insomnia	7.5% 11/146 • Time from first treatment up to 688 days
Renal and urinary disorders Haematuria	17.8% 26/146 • Time from first treatment up to 688 days
Reproductive system and breast disorders Vaginal haemorrhage	7.5% 11/146 • Time from first treatment up to 688 days
Respiratory, thoracic and mediastinal disorders Cough	8.9% 13/146 • Time from first treatment up to 688 days
Skin and subcutaneous tissue disorders Pruritus	11.6% 17/146 • Time from first treatment up to 688 days
Skin and subcutaneous tissue disorders Rash	16.4% 24/146 • Time from first treatment up to 688 days
General disorders Fatigue	9.6% 14/146 • Time from first treatment up to 688 days

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place