Abstract 4395
Background
In BMA117159, GSK2857916, a humanised (IgG1), afucosylated, anti-BCMA monoclonal antibody conjugated to monomethyl auristatin-F, has shown clinical activity (overall response rate [ORR]=60%; mPFS 12 months [95% CI, 3.1–NE]) as monotherapy in heavily pre-treated patients with MM. Pre-clinical data indicate that GSK’916 induces immunogenic cell death that activates dendritic cells and an antigen-specific T-cell response. PD-L1 overexpression may be a mechanism of immune evasion in MM. Pembrolizumab, a selective, humanised IgG4 anti-PD-1 monoclonal antibody that blocks the interaction of PD-1 with PD-L1 and PD-L2, may synergise with immunomodulatory drugs to enhance tumor suppression. T-cell-dependent antitumor response induced by GSK’916 may be augmented by combining with pembrolizumab.
Trial design
DREAMM 4 is a Phase I/II, single-arm, open-label, two-part study to evaluate safety and determine the recommended Phase 2 dose (RP2D) and clinical activity of GSK’916 in combination with pembrolizumab in patients with RRMM previously treated with ≥3 prior lines. Part 1 (dose escalation) will evaluate two doses of GSK’916 with a fixed dose of pembrolizumab in up to 12 participants. Modified Toxicity Probability Interval design will guide GSK’916 dose escalation. Primary objectives of Part 1 are to define safety and tolerability and define the RP2D dose of GSK’916 combined with pembrolizumab. Part 2 (dose expansion) will evaluate clinical activity of the RP2D, confirm safety, and collect pharmacokinetic information for GSK’916 in up to 28 participants. Dose expansion may stop early for futility at interim analysis. An additional stopping rule may stop enrolment early if the observed rate of treatment-related ≥Grade 4 AEs equals or exceeds the specified rate (12%). Part 2 objectives are to assess the ORR and confirm the safety profile of GSK’916 and pembrolizumab. Patients will continue combination treatment for 35 cycles or until progression, intolerance, consent withdrawal or death. Enrolment began in March 2019 and is ongoing.
Clinical trial identification
NCT03848845 (Rel. 19Feb2019).
Editorial acknowledgement
Clare Slater, PhD, of Fishawack Indicia Ltd, UK, funded by GlaxoSmithKline (GSK).
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline and is in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Disclosure
S. Trudel: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: GlaxoSmithKline. A. Nooka: Honoraria (self), Advisory / Consultancy: Emory University Winship Cancer Institute; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: Adaptive; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Spectrum; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): KITE pharmaceuticals. D. Fecteau: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. M. Talekar: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. R.C. Jewell: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. D. Williams: Full / Part-time employment: GlaxoSmithKline. J. Evans: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. J. Opalinska: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline.
Resources from the same session
2728 - MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
3197 - Genomic Alterations, Tumor Mutation Burden and Prognosis of Chinese Cardiac Sarcoma Patients
Presenter: Na Zhu
Session: Poster Display session 1
Resources:
Abstract
4214 - Evaluation of a peptide-conjugated alkylator melflufen in osteosarcoma preclinical models
Presenter: Konstantin Byrgazov
Session: Poster Display session 1
Resources:
Abstract
2654 - Expression analysis of NHEJ and HR genes in Ewing sarcomas: indications of DSB repair dysfunction
Presenter: Anastasios Kyriazoglou
Session: Poster Display session 1
Resources:
Abstract
4383 - Epidemiology of Synovial Sarcoma in EU28 countries
Presenter: Nedra Joseph
Session: Poster Display session 1
Resources:
Abstract
1937 - Resection Of High-Grade Large Soft Tissue Sarcoma With Adequate Wide Margin Can Lead To Good Local Control Without Adjuvant Radiotherapy
Presenter: Toshiyuki Kunisada
Session: Poster Display session 1
Resources:
Abstract
3757 - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models
Presenter: Marta Mendiola
Session: Poster Display session 1
Resources:
Abstract
1040 - EREMISS: Efficacy of regorafenib (REG) as maintenance therapy in non-adipocytic soft tissue sarcomas (STS) having received 1st-line doxorubicin-based chemotherapy (Doxo-CT)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
1048 - A Phase 2 biomarker-driven study evaluating the clinical efficacy of an MDM2 inhibitor, milademetan, in patients with intimal sarcoma, a disease with a high unmet need
Presenter: Kan Yonemori
Session: Poster Display session 1
Resources:
Abstract
1511 - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract