MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

Summary

The main purpose of this Phase I study was to test MSB0011359C (M7824) at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Phase I means the study drug has not previously been given to humans or has only been given to a limited number of people, although it has been extensively studied in animals. Based on this information, it is hoped to find out which dose could be best for the treatment of patients. There are two parts of this research study: a dose-escalation part and an expansion part. Dose escalation means that the first people taking part in the study will receive low doses of the study drug, and as more people take part, the additional participants will receive a higher dose. This is done to find the safest dose for the study drug. Expansion means that after the dose-escalation part of the study has looked at the safety and effectiveness of different doses, many more people will be invited to take part in the study and will receive the study drug at the safest dose. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Timeline

Start

2015-08-31

Primary completion

2022-05-23

Completion

2022-05-23

Publications

• Results Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C, Lamping E, Burmeister A, Marte JL, Cordes LM, Bilusic M, Karzai F, Ojalvo LS, Jehl G, Rolfe PA, Hinrichs CS, Madan RA, Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer. 2020 Dec;8(2):e001395. doi: 10.1136/jitc-2020-001395.
• Results Cho BC, Daste A, Ravaud A, Salas S, Isambert N, McClay E, Awada A, Borel C, Ojalvo LS, Helwig C, Rolfe PA, Gulley JL, Penel N. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort. J Immunother Cancer. 2020 Jul;8(2):e000664. doi: 10.1136/jitc-2020-000664.
• Results Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.
• Results Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3.
• Results Tan B, Khattak A, Felip E, Kelly K, Rich P, Wang D, Helwig C, Dussault I, Ojalvo LS, Isambert N. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-beta and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19.
• Rajan A, Abdul Sater H, Rahma O, Agajanian R, Lassoued W, Marte JL, Tsai YT, Donahue RN, Lamping E, Bailey S, Weisman A, Walter-Rodriguez B, Ito R, Vugmeyster Y, Sato M, Machl A, Schlom J, Gulley JL. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with advanced non-small cell lung cancer. J Immunother Cancer. 2024 Mar 13;12(3):e008480. doi: 10.1136/jitc-2023-008480.
• Spira A, Awada A, Isambert N, Lorente D, Penel N, Zhang Y, Ojalvo LS, Hicking C, Rolfe PA, Ihling C, Dussault I, Locke G, Borel C. Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer. Front Oncol. 2022 Dec 8;12:981940. doi: 10.3389/fonc.2022.981940. eCollection 2022.
• Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.

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