Identification of

Background

We report the clinical activity, safety, and identification of a predictive biomarker for bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβRII (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1, in patients with advanced triple-negative breast cancer (TNBC).

Methods

In this expansion cohort of a global phase 1 study, patients with pretreated, advanced TNBC received bintrafusp alfa 1200 mg every 2 weeks intravenously until disease progression, unacceptable toxicity, or withdrawal. The primary objective was confirmed best overall response by RECIST 1.1 assessed per independent review committee (IRC).

Results

As of May 15, 2020, a total of 33 patients had received bintrafusp alfa, for a median of 6.0 (range, 2.0-48.1) weeks. The objective response rate was 9.1% (95% CI, 1.9%-24.3%) by IRC and investigator assessment. The median progression-free survival per IRC was 1.3 (95% CI, 1.2-1.4) months, and median overall survival was 7.7 (95% CI, 2.1-10.9) months. Twenty-five patients (75.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 patients (15.2%); no patients had a grade 4 TRAE. There was 1 treatment-related death (dyspnea, hemolysis, and thrombocytopenia in a patient with extensive disease at trial entry). Responses occurred independently of PD-L1 expression, and tumor RNAseq data identified

Conclusions

Bintrafusp alfa showed clinical activity and manageable safety in patients with heavily pretreated advanced TNBC.

ClinicalTrialsgov identifier

NCT02517398.

Informations de copyright

Copyright © 2022 Spira, Awada, Isambert, Lorente, Penel, Zhang, Ojalvo, Hicking, Rolfe, Ihling, Dussault, Locke and Borel.

Déclaration de conflit d'intérêts

AA has received travel grants and advisory/speaker fees for Novartis, Roche, Eli Lilly, Amgen, Eisai, Bristol Myers Squibb, Pfizer, MSD, LEO Pharma, and Genomic Health. YZ is employed by Karyopharm Therapeutics and was employed by EMD Serono, Billerica, MA, USA, and owns stock in Moderna. LSO is employed by Bristol Myers Squibb and was employed by EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. ID is employed by Fusion Pharmaceuticals, Inc and was employed by EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. GL is employed by Senda Biosciences and was employed by EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. PAR is employed by EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. CH and CI are employed by Merck. CB has received consulting fees from Bristol Myers Squibb, AstraZeneca, and Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.