Abstract 1689P
Background
Bintrafusp alfa, an investigational, 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, has displayed clinical activity and manageable safety in patients with heavily pretreated solid tumors from two phase I studies (NCT02517398 and NCT02699515). Although bintrafusp alfa–associated adverse events (AEs) are mostly mild to moderate, effective management is essential to minimize disruptions in treatment and maintain quality of life (QOL). Here, we provide guidance for the early identification and management of AEs associated with bintrafusp alfa, particularly those related to TGF-β inhibition, with the aim of optimizing patients’ treatment experience and outcomes.
Methods
Guidance was developed based on experience from 606 patients in two phase I clinical trials that evaluated safety and efficacy of bintrafusp alfa in advanced solid tumors. Management approaches are presented to mitigate the impact of these AEs on patients and potentially increase treatment duration.
Results
Overall, treatment-related AEs (TRAEs) occurred in 414 patients (68.3%), with 135 patients (22.3%) having grade ≥3 TRAEs, and 53 patients (8.7%) permanently discontinuing treatment due to TRAEs. AEs of special interest include immune-related AEs (irAEs; rash, pruritus, endocrinopathies and other AEs commonly seen with PD-[L]1 inhibitors), and AEs associated with TGF-β inhibition (skin lesions, bleeding events, and anemia). Since lack of awareness of TGF-β–related toxicities is a concern, appropriate management could avoid unnecessary treatment discontinuation and potential misdiagnosis and over-treatment. Combining insight from prior experience with TGF-β and PD-(L)1 inhibitors can support early AE recognition and effective intervention.
Conclusions
Although most bintrafusp alfa–associated AEs were mild to moderate, timely and effective management strategies to mitigate the impact of common AEs could improve QOL for patients, contribute to increased time on treatment, and improve patient outcomes.
Clinical trial identification
NCT02517398 and NCT02699515.
Editorial acknowledgement
Medical writing support was provided by Ravi Subramanian, PhD, of ClinicalThinking, Inc, Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.
Disclosure
J. Gulley: Financial Interests, Institutional, Other, NCI Has A Cooperative Research And Development Agreement: EMD Serono/Merck KGaA. M.E. Lacouture: Financial Interests, Personal, Advisory Role: EMD Serono. A. Spira: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi. H. Verdaguer Mata: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. C. Yoo: Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Ono Pharmaceuticals; Financial Interests, Personal, Research Grant: Ispen; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: HK inno.N; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Ispen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Stocks/Shares: OncoCross; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: HK inno.N; Financial Interests, Personal, Speaker’s Bureau: Debio Pharm; Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin; Financial Interests, Personal, Speaker’s Bureau: Boryung Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Janssen. B.C. Cho: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MOGAM Institute; Financial Interests, Institutional, Research Grant: Dong-A ST; Financial Interests, Institutional, Research Grant: Champions Oncology; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Yuhan; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Dizai Pharma; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Medpacto; Financial Interests, Institutional, Research Grant: GI Innovation; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Interpark Bio Convergence Corp; Financial Interests, Personal, Advisory Role: Kanaph Therapeutic Inc.; Financial Interests, Personal, Advisory Role: Brigebio Therapeutics; Financial Interests, Personal, Advisory Role: Cyrus Therapeutics; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc.; Financial Interests, Personal, Stocks/Shares: Gencurix Inc.; Financial Interests, Personal, Stocks/Shares: Bridgebio Therapeutics; Financial Interests, Personal, Stocks/Shares: Kanaph Therapeutic Inc.; Financial Interests, Personal, Stocks/Shares: Cyrus Therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio Convergence Corp.; Financial Interests, Personal, Other, Consulting Role: Novartis; Financial Interests, Personal, Other, Consulting Role: AstraZeneca; Financial Interests, Personal, Other, Consulting Role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting Role: Roche; Financial Interests, Personal, Other, Consulting Role: Bristol-Myers Squibb; Financial Interests, Personal, Other, Consulting Role: Ono; Financial Interests, Personal, Other, Consulting Role: Yuhan; Financial Interests, Personal, Other, Consulting Role: Pfizer; Financial Interests, Personal, Other, Consulting Role: Eli Lilly; Financial Interests, Personal, Other, Consulting Role: Janssen; Financial Interests, Personal, Other, Consulting Role: Takeda; Financial Interests, Personal, Other, Consulting Role: MSD; Financial Interests, Personal, Other, Consulting Role: Medpacto; Financial Interests, Personal, Other, Consulting Role: Blueprint Medicines; Financial Interests, Personal, Other, Board of Director: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. C. Helwig: Financial Interests, Personal, Full or part-time Employment: Merck KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Merck KGaA, Darmstadt, Germany. T. Halady: Financial Interests, Personal, Full or part-time Employment: Merck KGaA, Darmstadt, Germany. C. Valencia: Financial Interests, Personal, Full or part-time Employment: EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany. M. Bajars: Financial Interests, Personal, Full or part-time Employment: EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany. J. Strauss: Financial Interests, Personal, Other, Listed as coinventor on an NIH patent: National Institutes of Health. All other authors have declared no conflicts of interest.