ArticleCancer chemotherapy and pharmacology2022
Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1.
Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, PK, Biological and Clinical Activity of MSB0011359C in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia
A Phase Ib/II, Open-Label Study of M7824 in Combination With Chemotherapy in Participants With Stage IV Non-small Cell Lung Cancer
A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With Advanced, Unresectable Cervical Cancer With Disease Progression During or After Platinum-Containing Chemotherapy
Who cites it
11 citing papers in PubMed.
- Blockade of Tumor-Intrinsic TGFβ Signaling Drives Hyperprogression in Small Cell Lung Cancer.Cancer discovery · 2026Article
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Linavonkibart and pembrolizumab in immune checkpoint blockade-resistant advanced solid tumors: a phase 1 trial.Nature medicine · 2026Article
- Phase I Clinical Trial of the Bifunctional EGFR/TGF-β Fusion Protein Ficerafusp Alfa (BCA101) Alone and in Combination with Pembrolizumab for Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC.JTO clinical and research reports · 2025Article
- Transforming growth factor-β receptors: versatile mechanisms of ligand activation.Acta pharmacologica Sinica · 2024Review
- First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors.BMC cancer · 2024Article
- Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Discovery and preclinical evaluation of BPB-101: a novel triple functional bispecific antibody targeting GARP-TGF-β complex/SLC, free TGF-β and PD-L1.Frontiers in immunology · 2024Article
- Tumor growth inhibition modeling in patients with second line biliary tract cancer and first line non-small cell lung cancer based on bintrafusp alfa trials.CPT: pharmacometrics & systems pharmacology · 2024Article
- A multistate modeling and simulation framework to learn dose-response of oncology drugs: Application to bintrafusp alfa in non-small cell lung cancer.CPT: pharmacometrics & systems pharmacology · 2023Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the transforming growth factor-β (TGF-β) receptor II fused to a human immunoglobulin G1 antibody blocking programmed death ligand 1 (PD-L1). The recommended phase 2 dose (RP2D) was selected based on phase 1 efficacy, safety, and pharmacokinetic (PK)-pharmacodynamic data, assuming continuous inhibition of PD-L1 and TGF-β is required. Here, we describe a model-informed dose modification approach for risk management of BA-associated bleeding adverse events (AEs).
methodsThe PK and AE data from studies NCT02517398, NCT02699515, NCT03840915, and NCT04246489 (n = 936) were used. Logistic regression analyses were conducted to evaluate potential relationships between bleeding AEs and BA time-averaged concentration (C
resultsThe probability of bleeding AEs increased with increasing C
conclusionA pragmatic model-informed approach for management of bleeding AEs was implemented in ongoing clinical trials of BA. This approach is expected to improve benefit-risk profile; however, its effectiveness will need to be evaluated based on safety data generated after implementation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.