NCT04349280

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

Terminated Phase 1 Results posted Last updated 18 April 2024

What this trial tests

Phase 1 trial testing Bintrafusp alfa in Neoplasms in 25 participants. Terminated before completion.

Timeline

15 October 2020

Primary endpoint
15 August 2022

15 August 2022

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	25
Start date	15 October 2020
Primary completion	15 August 2022
Estimated completion	15 August 2022
Sites	12 locations across France, Netherlands, Canada, United States, Spain

Drugs / interventions tested

• Bintrafusp alfa — full drug profile →

Conditions studied

• Neoplasms — all drugs for Neoplasms →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Primary · 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 n

Group	Value	95% CI
Main Study - Bintrafusp Alfa	20.0	6.83 – 40.70

Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) Secondary · 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.

Treatment Emergent AEs

Group	Value	95% CI
Main Study - Bintrafusp Alfa	25

Treatment Emergent SAEs

Group	Value	95% CI
Main Study - Bintrafusp Alfa	17

Number of Participants With Worst Grade Treatment Emergent AEs Secondary · 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 1

Group	Value	95% CI
Main Study - Bintrafusp Alfa	1

Grade 2

Group	Value	95% CI
Main Study - Bintrafusp Alfa	6

Grade 3

Group	Value	95% CI
Main Study - Bintrafusp Alfa	15

Grade 4

Group	Value	95% CI
Main Study - Bintrafusp Alfa	1

Grade 5

Group	Value	95% CI
Main Study - Bintrafusp Alfa	2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Main Study - Bintrafusp Alfa

Serious: 17/25 (68%)

Deaths: 12/25

PACT Phase - Bintrafusp Alfa

Serious: 1/1 (100%)

Deaths: 0/1

Serious adverse events (17 terms)

Reaction	System	Main Study - Bintrafusp Alfa	PACT Phase - Bintrafusp Alfa
Urinary tract infection	Infections and infestations	—	—
Pyrexia	General disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
General physical health deterioration	General disorders	—	—
Mucosal inflammation	General disorders	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Pseudomonal sepsis	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Blood creatinine increased	Investigations	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Haemorrhage intracranial	Nervous system disorders	—	—
Delirium	Psychiatric disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Nephropathy	Renal and urinary disorders	—	—
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (37 terms — click to expand)

Reaction	System	Main Study - Bintrafusp Alfa	PACT Phase - Bintrafusp Alfa
Anaemia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Fatigue	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Mucosal inflammation	General disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Blood creatinine increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Haematuria	Renal and urinary disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Tachycardia	Cardiac disorders	—	—
Hyperthyroidism	Endocrine disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Haematochezia	Gastrointestinal disorders	—	—
Chills	General disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Cell death	Metabolism and nutrition disorders	—	—
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Neuralgia	Nervous system disorders	—	—
Depression	Psychiatric disorders	—	—
Pelvic pain	Reproductive system and breast disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Urinary tract infection, Pyrexia, Anaemia, Colitis, General physical health deterioration, Mucosal inflammation, COVID-19 pneumonia, Pseudomonal sepsis.

Data from ClinicalTrials.gov NCT04349280 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
   Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
2. Novel therapies emerging in oncology to target the TGF-β pathway.
   Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, et al · · 2021 · cited 336× · PMID 33823905 · DOI 10.1186/s13045-021-01053-x
3. Targeting TGFβ signal transduction for cancer therapy.
   Liu S, Ren J, Ten Dijke P. · · 2021 · cited 302× · PMID 33414388 · DOI 10.1038/s41392-020-00436-9
4. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
5. Development of Immunotherapy Combination Strategies in Cancer.
   Yap TA, Parkes EE, Peng W, Moyers JT, et al · · 2021 · cited 260× · PMID 33811048 · DOI 10.1158/2159-8290.cd-20-1209
6. Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.
   Shi ZD, Pang K, Wu ZX, Dong Y, et al · · 2023 · cited 168× · PMID 36906600 · DOI 10.1038/s41392-023-01383-x
7. Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment.
   Gulley JL, Schlom J, Barcellos-Hoff MH, Wang XJ, et al · · 2022 · cited 132× · PMID 34854206 · DOI 10.1002/1878-0261.13146
8. TGF-beta signal transduction: biology, function and therapy for diseases.
   Tie Y, Tang F, Peng D, Zhang Y, et al · · 2022 · cited 97× · PMID 36534225 · DOI 10.1186/s43556-022-00109-9