Abstract CT267: A phase 1b/2, open-label study of bintrafusp alfa with chemotherapy in patients with stage IV non-small cell lung cancer
Authors: Barlesi Fabrice , Hiret Sandrine , Rolfo Christian , Grenga Italia , Köenig Andre , Vugmeyster Yulia , Horn Leora 
Published: September 2020

Abstract
Background: The combinations of pembrolizumab plus chemotherapy (CT) and atezolizumab plus bevacizumab and CT have been approved for first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) regardless of PD-L1 expression; however, there is still a significant unmet need for this patient population who may not respond to immune checkpoint treatment. Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor designed to function as a TGF-β “trap” fused to a human IgG1 mAb blocking PD-L1. Promising antitumor activity and a manageable safety profile were observed with bintrafusp alfa in multiple cohorts of a phase 1 study (NCT02517398) that enrolled patients with advanced, pretreated NSCLC who experienced disease progression either after platinum-based CT or anti-PD-(L)1 monotherapy. This study is evaluating the safety and efficacy of bintrafusp alfa in combination with CT in patients with stage IV NSCLC.
Trial Design: This is a phase 1b/2, open-label, 4-cohort study (NCT03840915) evaluating bintrafusp alfa in combination with CT in patients with stage IV NSCLC. All patients will receive bintrafusp alfa 2400 mg Q3W intravenously and either cisplatin or carboplatin + pemetrexed (cohort A), carboplatin + nab-paclitaxel or paclitaxel (cohort B), cisplatin or carboplatin + gemcitabine (cohort C), or docetaxel (cohort D) Q3W for 4 cycles, followed by bintrafusp alfa maintenance (monotherapy or combination with pemetrexed [cohort A]) for up to 31 cycles or until disease progression, unacceptable toxicity, or death. Patients must be adults with histologically confirmed diagnosis of stage IV nonsquamous or squamous NSCLC (nonsquamous for cohort A), adequate organ function, ECOG PS ≤1, life expectancy ≥3 months, and measurable disease based on RECIST 1.1. Patients in cohorts A-C must not have received prior systemic therapy, and patients in cohort D must have disease progression on previous anti-PD-(L)1 therapy. Patients with tumors with actionable mutations (for which targeted therapy is locally approved), mixed SCLC and NSCLC, active CNS metastases, active autoimmune disease, known severe hypersensitivity, or interstitial lung disease are not eligible. The primary endpoint of this study is to assess the safety of bintrafusp alfa in combination with CT. Planned enrollment is 64 patients (32 patients among the 4 cohorts during the safety phase, and an additional 32 patients in cohort A for expansion phase).
Citation Format: Fabrice Barlesi, Sandrine Hiret, Christian Rolfo, Italia Grenga, Andre Köenig, Yulia Vugmeyster, Leora Horn. A phase 1b/2, open-label study of bintrafusp alfa with chemotherapy in patients with stage IV non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT267.