Abstract 1272P
Background
Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Results from a global phase 1 study (NCT02517398) found an objective response rate (ORR) of 27.5%, median overall survival (OS) of 17.1 months, and a manageable safety profile in patients who received bintrafusp alfa 1200 mg every 2 weeks (Q2W) in the 2L setting at 2 years of follow-up. Here we present efficacy and safety data for 3 years of follow up.
Methods
Patients with advanced NSCLC, unselected for PD-L1 expression, who had disease progression after platinum-based 1L treatment with no prior immunotherapy were randomized to receive bintrafusp alfa at the recommended phase 2 dose of 1200 mg (n=40) Q2W until disease progression, unacceptable toxicity, or trial withdrawal. The primary objective was best overall response per RECIST 1.1. Secondary and exploratory objectives included safety, duration of response (DOR), and OS.
Results
As of March 31, 2020, 40 patients received bintrafusp alfa 1200 mg Q2W for a median of 16.9 (range, 2-160) weeks. The median follow-up was 153.3 weeks, and 16 patients were still alive; 2 patients had an ongoing response, and 1 patient remained on treatment. The median DOR was 18 months and 21.2% (n=2) of patients had responses lasting ≥24 months. The 12-, 24-, and 36-month OS rates were 66.2%, 39.7%, and 23.2%, respectively. By subgroups of PD-L1 expression, the median OS was 21.7 months in PD-L1 positive (≥1%) patients and not reached in patients with high PD-L1 expression (≥80% by 73-10 assay). The 36-month OS rate was 33.6% in PD-L1 positive patients and 66.7% in patients with high PD-L1 expression. No new safety signals were observed.
Conclusions
After 3 years of follow-up, bintrafusp alfa at 1200 mg Q2W as 2L therapy continues to show durable responses and long-term survival with a manageable toxicity profile in patients with advanced NSCLC. A phase 3 study evaluating bintrafusp alfa vs pembrolizumab as 1L treatment for patients with advanced NSCLC that has high PD-L1 expression is ongoing (NCT03631706).
Clinical trial identification
NCT02517398.
Editorial acknowledgement
Medical writing support was provided by Megan Hyde, PharmD, of ClinicalThinking, Inc, which was funded by Merck KGaA and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck, KGaA, Darmstadt, Germany and GlaxoSmithKline.
Disclosure
L. Paz-Ares: Honoraria (self): Adacap; Honoraria (self): Amgen; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicines; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Incyte; Honoraria (self): Ipsen; Honoraria (self): Merck; Honoraria (self), Research grant/Funding (institution): Merck Sharp and Dohme; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Servier; Honoraria (self): Sysmex; Honoraria (self): Takeda; Leadership role: Altum sequencing; Officer/Board of Directors: Genómica. T.M. Kim: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Takeda; Advisory/Consultancy: Voronoi; Advisory/Consultancy: Boryung; Research grant/Funding (self): AstraZeneca-KHIDI. E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Guardant Health; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck KGaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Prime Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Springer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Touchime; Research grant/Funding (institution): EMD Serono; Officer/Board of Directors: Grifols (Independent Member of the Board of Directors). D.H. Lee: Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): ChongKunDang; Honoraria (self): Eli Lilly; Honoraria (self): GreenCross Corp; Honoraria (self): Janssen; Honoraria (self): Menarini; Honoraria (self): Merck KGaA; Honoraria (self): MSD; Honoraria (self): Mundipharma; Honoraria (self): Novartis; Honoraria (self): Ono; Honoraria (self): Roche; Honoraria (self): ST Cube; Honoraria (self), Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: Blueprint Medicine. K.H. Lee: Honoraria (self): BMS; Honoraria (self): MSD; Advisory/Consultancy: AstraZeneca. C-C. Lin: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Roche; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Takeda; Travel/Accommodation/Expenses: BeiGene; Travel/Accommodation/Expenses: Eli Lilly. M.J. Flor: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Novartis; Honoraria (self): Eisai; Honoraria (self): KYOWA KIRIN; Honoraria (self): AGELINI; Honoraria (self): Grunenthal. R.M. Alvarez: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: PharmaMar; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Blueprint Medicine; Research grant/Funding (institution): Boehringer Ingelheim. C. Helwig: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck KGaA. L.S. Ojalvo: Licensing/Royalties, Full/Part-time employment: EMD Serono. J. Gulley: Research grant/Funding (institution): Merck KGaA. B.C. Cho: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MOGAM Institute; Honoraria (self), Research grant/Funding (institution): Dong-A ST; Honoraria (self), Research grant/Funding (institution), Licensing/Royalties: Champions Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Yuhan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Dizal Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): Medpacto; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): GIInnovation; Shareholder/Stockholder/Stock options: TheraCanVac Inc; Shareholder/Stockholder/Stock options: Gencurix Inc; Shareholder/Stockholder/Stock options: Bridgebio therapeutics; Shareholder/Stockholder/Stock options: KANAPH; Shareholder/Stockholder/Stock options: Therapeutic Inc; Full/Part-time employment: Yonsei University; Officer/Board of Directors: Daan Biotherapeutics; Advisory/Consultancy: BMS. All other authors have declared no conflicts of interest.