Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 2254 |
| INN | Bintrafusp alfa |
| Status | Terminated |
| Drug code(s) | M7824, MSB0011359C |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Bispecific, Immunoconjugate |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | TGF beta binding domain |
| Discovery method/technology | None |
| Target(s) | PD-L1, TGF beta |
| Indications of clinical studies | Soft-tissue Sarcoma, Triple Negative Breast Neoplasms, Nasopharyngeal Carcinoma, Uterine Cervical Neoplasms, non-small cell lung cancer, biliary tract cancer, solid tumors |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Terminated at Phase 3 |
| Status | Inactive |
| Start of clinical phase (IND filing or first Phase 1) | September 09, 2015 |
| Start of Phase 2 | February 15, 2019 |
| Start of Phase 3 | October 19, 2018 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | EMD Serono |
| Licensee/Partner | GSK |
| Comments about company or candidate | Not listed in Merck or EMD Serono pipelines as of Aug 2023; assumed to be terminated, although clinical studies sponsored by NCI are ongoing. NCT05061823 Phase 3 Follow-up Study to Collect Long-term Data on Participants From Multiple Bintrafusp Alfa (M7824) Clinical Studies (INTR@PID 054) still recruiting as of last update or record in Jan 2022. September 30, 2021 I Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced a mutual decision with GSK to terminate their agreement on bintrafusp alfa, effective September 30, 2021. The decision is based on the clinical trial data generated to date, most notably the previously reported results from the INTR@PID Lung 037 study, which did not replicate the encouraging data observed in earlier studies. Based on the data generated during the agreement, no milestone payments were made by GSK and no future milestone obligations remain. Aug 2021: Phase 2 INTR@PID BTC 055 study of the drug alongside chemotherapy as a first-line treatment for patients with locally advanced or metastatic biliary tract cancer (BTC) has been abandoned early. An interim look at the data by the trial’s independent monitoring committee concluded that adding bintrafusp alfa to a gemcitabine/cisplatin regimen was unlikely to show any improvement on overall survival than the chemotherapy on its own. The failure comes after bintrafusp alfa missed the mark in a phase 2 trial as a second-line monotherapy for BTC patients who failed first-line chemotherapy in March, when GSK and Merck suggested the first-line study was the brightest prospect for the drug. In January, it also failed to show any improvement over Merck & Co/MSD’s checkpoint inhibitor Keytruda (pembrolizumab) in previously-untreated patients with PD-L1-positive non-small cell lung cancer (NSCLC). NCT04457778 Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa, Anti-PDL1/ TGFß Trap in, Participants With Metastatic or Locally Advanced Solid Unresectable Tumors. NCT03631706 Phase 3 in NSCLC started in Oct 2018. NCT04066491 Phase 2/3 study in biliary tract cancer started in Sep 2019. NCT03833661 Phase 2 study in Locally Advanced or Metastatic Biliary Tract Cancer due to start in March 2019 (not yet recruiting in Feb). October 22, 2018: Merck KGaA, Darmstadt, Germany, which operates its healthcare business in the U.S. and Canada as EMD Serono, today announced new and updated results from expansion cohorts of two ongoing M7824 Phase I clinical trials (NCT02517398 and NCT02699515) at the ESMO (European Society for Medical Oncology) 2018 Congress in Munich, October. New data presented include the first presentation of results for M7824 in advanced squamous cell carcinoma of the head and neck (SCCHN), biliary tract cancer (BTC) and esophageal cancers (esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma [EAC]). In addition, updated data for M7824 in non-small cell lung cancer (NSCLC) and gastric cancer add to the growing evidence for M7824's clinical anti-tumor activity in a number of challenging cancers. Two Phase 1 studies recruiting as of Aur 15 2017; half-life of 4-8 days |
| Full address of company | One Technology Place, Rockland, MA 02370 North America United States of America https://www.emdserono.com/us-en/company/contact-us.html |
Immune checkpoint inhibitor. Anti-PDL1 antibody fused at each Fc terminus to TGF beta binding domain. Bifunctional immunotherapy. Dual-acting fusion protein neutralizes two immuno-inhibitory pathways. The novel bifunctional fusion protein M7824 (MSB0011359C) is a fully human IgG1 monoclonal antibody against PD-L1, fused via a glycine-serine linker at the CH 3 -C terminus to the extracellular domain of human TGFβ receptor II, which functions as a TGFβ “trap.” Thus, M7824 is designed to exert independent and complementary anti-immunosuppressive functions by simultaneously blocking the PD-L1 and TGFβ pathways. Description from WHO proposed INN list 119: human immunoglobulin G1-lambda, anti-[human programmed cell death 1 ligand 1 (PD-L1, programmed death ligand 1, PDCD1 ligand 1, B7 homolog 1, B7-H1, CD274)], human monoclonal antibody,anti-(human programmed death ligand 1) immunoglobulin G1, lambda light chain, fused at the C-terminus of both heavy chains via a peptidyl linker (450-471), to a fragment of the mature human extracellular domain of human TGF-beta receptor type-2 (TGFR-2, TGFBR2, transforming growth factor-beta receptor type II)TGFβ type II receptor (472607), dimer, produced in Chinese hamster ovary (CHO) cells, glycoform alfa
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |