A First-in-Human Study of cinrebafusp alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.

Autor:	Piha-Paul S; The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Olwill SA; Pieris Pharmaceuticals, Freising, Germany., Hamilton E; Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee, United States., Tolcher A; South Texas Accelerated Research Therapeutics, San Antonio, TX, United States., Pohlmann P; The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Liu SV; Georgetown University, Washington, DC, United States., Wurzenberger C; Pieris Pharmaceuticals, Hallbergmoos, Germany., Hasenkamp LC; Pieris Pharmaceuticals, Freising, Germany., Hansbauer EM; Pieris Pharmaceuticals, Hallbergmoos, Germany., Shroff R; University of Arizona, Tucson, AZ, United States., Hurvitz S; Fred Hutchinson Cancer Center, Seattle, WA, United States., Krishnamurthy A; Hillman Cancer Center, Pittsburgh, United States., Patnaik A; South Texas Accelerated Research Therapeutics, San Antonio, United States., Hahn N; Johns Hopkins School of Medicine, Baltimore, Maryland, United States., Kumar R; Pieris, Bavaria, Germany., Duerr M; Pieris Pharmaceuticals, Bavaria, Germany., Zettl M; CureVac (Germany), Tuebingen, Germany., Aviano K; Pieris Pharmaceuticals (United States), Massachusetts, United States., Matis L; Pieris Pharmaceuticals (United States), Massachusetts, United States., Bruns I; Bayer (United States), United States., Ku G; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Sep 05. Date of Electronic Publication: 2024 Sep 05.
DOI:	10.1158/1078-0432.CCR-24-1552
Abstrakt:	Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, natural killer cells and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies. Experimental Design: This was a multi-center dose escalation study involving patients with HER2-positive malignancies who had received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the maximum tolerated dose (MTD) and to observe any clinical activity at different dose levels. Results: Out of 40 evaluable patients in the 'active dose' efficacy cohorts, 5 showed an antitumor response, resulting in an overall response rate (ORR) of 12.5% and a disease control rate of 52.5%. Clinical activity was observed at the 8 mg/kg and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with Grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study. Conclusion: Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.
Databáze:	MEDLINE
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