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DRUG:

bintrafusp alfa (M7824)

i
Other names: M7824, MSB0011359C, MSB 0011359C, M-7824, GSK4045154, MSB-0011359C, GSK-4045154, GSK 4045154, M 7824
Company:
EMD Serono
Drug class:
PD-L1 inhibitor, TGFβ inhibitor
Related drugs:
5d
Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1) (clinicaltrials.gov)
P1/2, N=53, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed
Trial completion
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
|
TMB-H • MSI-H/dMMR
|
bintrafusp alfa (M7824) • epacadostat (INCB024360) • Anktiva (nogapendekin alfa inbakicept-pmln)
10d
Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON). (clinicaltrials.gov)
P2, N=11, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Jul 2024 | Trial primary completion date: Aug 2025 --> Jul 2024
Trial completion • Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824)
1m
NCI-2018-01184: M7824 in Treating Patients With Stage II-III HER2 Positive Breast Cancer (clinicaltrials.gov)
P1, N=20, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed
Trial completion
|
bintrafusp alfa (M7824)
2ms
Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON). (clinicaltrials.gov)
P2, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Aug 2024 --> Aug 2025
Trial primary completion date
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824)
2ms
Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
P2, N=32, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Aug 2024
Trial completion • Trial completion date • Metastases
|
CEACAM5 (CEA Cell Adhesion Molecule 5) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
2ms
Enrollment change • Metastases
|
bintrafusp alfa (M7824)
2ms
BIMES: Study of the Efficacy and Safety of the Bintrafusp Alfa in Previously Treated Advanced Malignant Pleural Mesothelioma (clinicaltrials.gov)
P2, N=47, Completed, Fundación GECP | Recruiting --> Completed | Trial completion date: Apr 2025 --> Feb 2024 | Trial primary completion date: Mar 2025 --> Feb 2024
Trial completion • Trial completion date • Trial primary completion date • Metastases
|
CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824)
2ms
Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma. (PubMed, Cancers (Basel))
While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy.
Review • Journal
|
TGFB1 (Transforming Growth Factor Beta 1)
|
bintrafusp alfa (M7824) • retlirafusp alfa (SHR-1701) • ficerafusp alfa (BCA101) • LY3200882 • dalantercept (ACE-041)
3ms
Dual A2A/ A2B adenosine receptor antagonist M1069 counteracts immuno-suppressive mechanisms of adenosine and reduces tumor growth in vivo. (PubMed, Mol Cancer Ther)
In vivo, M1069 decreased tumor growth as a monotherapy and enhanced anti-tumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout (KO) 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the anti-tumor activity of other agents, including BA and cisplatin.
Preclinical • Journal
|
CD73 (5'-Nucleotidase Ecto) • IL2 (Interleukin 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
|
cisplatin • bintrafusp alfa (M7824) • M1069
3ms
Efficacy and safety of bintrafusp alfa in two phase 1 expansion cohorts with advanced hepatocellular carcinoma. (PubMed, Hepatology)
Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.
P1 data • Journal • Metastases
|
TGFB1 (Transforming Growth Factor Beta 1)
|
sorafenib • bintrafusp alfa (M7824)
3ms
Trial completion • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • bintrafusp alfa (M7824)
4ms
Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial. (PubMed, JAMA Oncol)
This phase 2 nonrandomized controlled trial of bintrafusp alfa met its primary end point, which may support the potential of a bispecific therapy targeting transforming growth factor β and programmed cell death 1 ligand 1 in patients with recurrent or metastatic cervical cancer. ClinicalTrials.gov Identifier: NCT04246489.
Journal • Metastases
|
PD-L1 (Programmed death ligand 1)
|
bintrafusp alfa (M7824)
4ms
TAPESTRY: TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY (clinicaltrials.gov)
P=N/A, N=49, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Trial completion date: Jun 2023 --> Sep 2030 | Trial primary completion date: Jun 2023 --> Sep 2025
Trial completion date • Trial primary completion date • IO biomarker
|
carboplatin • paclitaxel • bintrafusp alfa (M7824)
4ms
Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer (clinicaltrials.gov)
P1/2, N=3, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; The sponsor decided to no longer develop the drug and stop support of studies using the drug.
Trial termination
|
bintrafusp alfa (M7824)
4ms
A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov)
P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
5ms
Enrollment change • Combination therapy • Metastases
|
CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824) • PDS01ADC
5ms
Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON). (clinicaltrials.gov)
P2, N=11, Active, not recruiting, National Cancer Institute (NCI) | N=32 --> 11
Enrollment change • Metastases
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824)
6ms
Trial completion • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824) • SX-682 • Panvac-VF (falimarev/inalimarev)
7ms
Bintrafusp Alfa in Previously Treated Patients With R/M Non-keratinizing NPC (clinicaltrials.gov)
P2, N=38, Completed, The University of Hong Kong | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jul 2023
Trial completion • Trial completion date • Metastases
|
bintrafusp alfa (M7824)
7ms
Study of M7824 and Paclitaxel Combination as a Second-line Treatment in Patients With Recurrent/Metastatic Gastric Cancer (clinicaltrials.gov)
P1/2, N=49, Completed, Yonsei University | Not yet recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jun 2025 --> Oct 2023 | Trial primary completion date: Sep 2024 --> Oct 2023
Trial completion • Phase classification • Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • CD4 (CD4 Molecule)
|
HER-2 negative
|
paclitaxel • bintrafusp alfa (M7824)
7ms
Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
PD-L1 negative
|
Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
7ms
A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer (clinicaltrials.gov)
P1, N=25, Terminated, GlaxoSmithKline | Active, not recruiting --> Terminated; Primary investigator withdrew the participant due to an SAE
Trial termination • Metastases
|
bintrafusp alfa (M7824)
7ms
Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1) (clinicaltrials.gov)
P1/2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=113 --> 53
Enrollment closed • Enrollment change
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
|
TMB-H • MSI-H/dMMR
|
bintrafusp alfa (M7824) • epacadostat (INCB024360) • Anktiva (nogapendekin alfa inbakicept-pmln)
7ms
Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses. (PubMed, Br J Cancer)
Our preclinical studies of BA in advanced ovarian cancer models support further testing of BA as an improved immunotherapy option for patients with advanced ovarian cancer.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TGFB1 (Transforming Growth Factor Beta 1)
|
PD-L1 expression • IFNG expression
|
bintrafusp alfa (M7824)
8ms
N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer (clinicaltrials.gov)
P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=28 --> 0 | Trial completion date: Aug 2026 --> Apr 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Nov 2024 --> Apr 2024
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • Combination therapy
|
CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln)
8ms
Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with advanced non-small cell lung cancer. (PubMed, J Immunother Cancer)
Bintrafusp alfa was observed to have modest clinical activity and manageable safety, and was associated with notable immunologic changes involving modulation of the tumor immune microenvironment in patients with advanced NSCLC.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • TGFB1 (Transforming Growth Factor Beta 1)
|
bintrafusp alfa (M7824)
9ms
Hyperprogressive disease following bintrafusp alfa and DNA damaging chemotherapy in relapsed small cell lung cancer (AACR 2024)
Cohort 1 enrolled patients with relapsed SCLC across Arms A (bintrafusp alfa 2400 mg q3 wks), B (bintrafusp alfa 2400 mg on D1 plus topotecan 1 mg/m2/day on D1-5 q3 wks), and C (bintrafusp alfa 1200 mg on D1 q2 wks plus temozolomide 200 mg/m2/day on D1-5 q4 wks). Concomitant TGF-beta and PD-L1 blockade is associated with a high frequency of HPD in SCLC patients. cfDNA could be critical for monitoring HPD. Tumor and blood immune signatures may inform the likelihood of HPD, with immune excluded tumors more likely to develop HPD.NCT Number: NCT03554473Bintrafusp alfa was provided by EMD Serono (CrossRef Funder ID: 10.13039/100004755)
Clinical • PD(L)-1 Biomarker • IO biomarker
|
IFNG (Interferon, gamma) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IL10 (Interleukin 10) • CCL19 (C-C Motif Chemokine Ligand 19) • TGFB1 (Transforming Growth Factor Beta 1) • CCL8 (C-C Motif Chemokine Ligand 8) • GZMH (Granzyme H)
|
DELFI-Tumor Fraction assay
|
temozolomide • topotecan • bintrafusp alfa (M7824)
9ms
LUNG 037: M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P3, N=304, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Mar 2024 --> Jun 2024
Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Keytruda (pembrolizumab) • bintrafusp alfa (M7824)
9ms
Hypofractionated Radiation Therapy and Bintrafusp Alfa for the Treatment of Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov)
P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
bintrafusp alfa (M7824)
9ms
Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (clinicaltrials.gov)
P2, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date
|
bintrafusp alfa (M7824) • Panvac-VF (falimarev/inalimarev) • ProstVac (rilimogene galvacirepvec)
9ms
M7824 and Topotecan or Temozolomide in Relapsed Small Cell Lung Cancers (clinicaltrials.gov)
P1/2, N=80, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2 | Trial primary completion date: Jan 2024 --> Jan 2025
Phase classification • Trial primary completion date • Tumor mutational burden
|
temozolomide • topotecan • bintrafusp alfa (M7824)
10ms
Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON). (clinicaltrials.gov)
P2, N=32, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2025
Enrollment closed • Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824)
10ms
Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma (clinicaltrials.gov)
P2, N=38, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2024 --> Dec 2024
Trial primary completion date
|
bintrafusp alfa (M7824)
10ms
21-C-0001: M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1/2, N=86, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
docetaxel • abiraterone acetate • prednisone • bintrafusp alfa (M7824) • PDS01ADC
11ms
Docetaxel With or Without Bintrafusp Alfa for the Treatment of Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=10, Terminated, Mayo Clinic | N=80 --> 10 | Trial completion date: Dec 2024 --> Dec 2023 | Active, not recruiting --> Terminated; EMD Serono recommendation based on three other studies that failed to show benefit for bintrafusp alfa
Enrollment change • Trial completion date • Trial termination • Metastases
|
docetaxel • bintrafusp alfa (M7824)
11ms
Phase 1 trial of first-line bintrafusp alfa in patients with locally advanced or persistent/recurrent/metastatic cervical cancer. (PubMed, Clin Cancer Res)
Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGF-β/PD-L1 inhibition in HPV-associated cancers, including cervical cancer.
P1 data • Journal • Metastases
|
TGFB1 (Transforming Growth Factor Beta 1)
|
Avastin (bevacizumab) • cisplatin • carboplatin • paclitaxel • bintrafusp alfa (M7824)
11ms
Bintrafusp Alfa and Pimasertib for the Treatment of Patients With Brain Metastases (clinicaltrials.gov)
P1/2, N=8, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Dec 2023 | Trial primary completion date: May 2025 --> Dec 2023
Trial completion • Trial completion date • Trial primary completion date
|
HR positive
|
bintrafusp alfa (M7824) • pimasertib (AS703026)
11ms
20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
CD4 (CD4 Molecule)
|
PD-L1 expression
|
bintrafusp alfa (M7824) • PDS01ADC
12ms
Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1) (clinicaltrials.gov)
P1/2, N=113, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
|
TMB-H • MSI-H/dMMR
|
bintrafusp alfa (M7824) • epacadostat (INCB024360) • Anktiva (nogapendekin alfa inbakicept-pmln)
12ms
First in Human Study of M6223 (clinicaltrials.gov)
P1, N=58, Completed, EMD Serono Research & Development Institute, Inc. | Active, not recruiting --> Completed
Trial completion
|
bintrafusp alfa (M7824) • dargistotug (M6223)
12ms
20-C-0104: HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers (clinicaltrials.gov)
P1/2, N=39, Active, not recruiting, National Cancer Institute (NCI) | N=20 --> 39 | Trial completion date: Oct 2023 --> Nov 2025
Enrollment change • Trial completion date
|
CD4 (CD4 Molecule)
|
bintrafusp alfa (M7824) • PRGN-2009
1year
M7824 Related Adverse Effects in Adults With Cancer (clinicaltrials.gov)
P=N/A, N=232, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
Trial completion date • Trial primary completion date • Adverse events
|
bintrafusp alfa (M7824)