Abstract 3946
Background
Toll-like receptor (TLR) activation can enhance a range of antitumor immune responses via production of inflammatory cytokines and modulation of immune cells in the tumor microenvironment. GSK1795091 is a synthetic TLR4 agonist that showed immunomodulatory activity in preclinical cancer models (Gao et al. J Clin Oncol 2018) and successfully completed a safety, pharmacokinetic (PK) and pharmacodynamic (PD) study using IV administration in healthy volunteers. The current study will evaluate GSK1795091 with immunotherapies that have highly complementary mechanisms of action and supporting preclinical data (e.g. GSK3174998 [an OX40 agonist], GSK3359609 [an ICOS agonist], or pembrolizumab [a PD-1 inhibitor]) with the aim of generating greater antitumor activity than with monotherapy.
Trial design
This is a Phase I, open-label, non-randomized study in patients (≥18 years) with advanced solid tumors who have progressed on, or are ineligible for, standard therapy. In Part 1, up to 72 patients will be divided into 3 arms: GSK1795091 (50–250 ng IV; dose escalation) plus either GSK3174998 (24 mg IV), GSK3359609 (80 mg IV), or pembrolizumab (200 mg IV). GSK1795091 will be given weekly for 12 weeks; combination partners will be administered every 3 weeks (q3w) from Week 3 to allow a 2-week GSK1795091 monotherapy run-in period. After Week 12, GSK1795091 will be administered q3w, coinciding with the combination partner. Up to 6 participants per dose level may be enrolled into a PK/PD cohort for each combination. In Part 2, initial expansion cohorts of up to 15 patients with head and neck squamous cell carcinoma will be enrolled in each treatment arm at the dose(s) identified in Part 1. The primary objective is to evaluate the safety and tolerability of GSK1795091 combination therapy. Additional objectives include clinical activity, PK, PD and immunogenicity. Enrollment for the GSK1795091 + GSK3174998 arm began in March 2018; 12 patients have completed the first 2 dose cohorts. The remaining arms will commence enrollment in 1Q2019. Funded by GlaxoSmithKline.
Clinical trial identification
NCT03447314.
Editorial acknowledgement
Medical writing and editorial assistance was provided by Leigh O’Connor-Jones, PhD, of Fishawack Indicia Ltd and was funded by GSK.
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
A.R. Hansen: Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Research grant / Funding (institution): Karyopharm Therapeutics. J. Strauss: Shareholder / Stockholder / Stock options: Abbvie; Shareholder / Stockholder / Stock options: Abbott Laboratories; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Shareholder / Stockholder / Stock options: Intuitive Surgical; Shareholder / Stockholder / Stock options: Johnson and Johnson; Shareholder / Stockholder / Stock options: Merck; Advisory / Consultancy, Consulting agreement in 2017, no longer active: Tempus; Advisory / Consultancy, Member of advisory board: Dialectic Therapeutics. J. Chaves: Research grant / Funding (self), Research grant / Funding (institution): Immune Design; Research grant / Funding (self), Research grant / Funding (institution): Zymeworks; Research grant / Funding (self), Research grant / Funding (institution): Calithera; Research grant / Funding (self), Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (self), Research grant / Funding (institution): Merck; Research grant / Funding (self), Research grant / Funding (institution): EMD Serono; Research grant / Funding (self), Research grant / Funding (institution): Novartis; Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (self), Research grant / Funding (institution): Genentech; Research grant / Funding (self), Research grant / Funding (institution): Array BioPharma; Research grant / Funding (self), Research grant / Funding (institution): Incyte; Research grant / Funding (self), Research grant / Funding (institution): Nektar; Research grant / Funding (self), Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (self), Research grant / Funding (institution): Regeneron; Research grant / Funding (self), Research grant / Funding (institution): Halozyme; Research grant / Funding (self), Research grant / Funding (institution): Tesaro. S.A. Piha-Paul: Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): XuanZhu; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Principa Biopharma; Research grant / Funding (institution): Helix BioPharma; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): BlueLink; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Pieris Pharmaceuticals; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Samumed. H. Park: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Regeneron. E. Garralda: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Principia Biopharma Inc.; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Genentech Inc; Research grant / Funding (institution): Loxo Oncology; Travel / Accommodation / Expenses: Menarini; Travel / Accommodation / Expenses: Glycotope; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck, Sharp & Dohme; Research grant / Funding (institution): Incyte Biosciences International; Research grant / Funding (institution): Pharma Mar, SA; Research grant / Funding (institution): Kura Oncology Inc; Research grant / Funding (institution): Macrogenics Inc; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: F. Hoffman/La Roche; Advisory / Consultancy: Ellipses Pharma; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Janssen Global Services; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Neomed Therapeutics Inc. C.J. Matheny: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. J. Carver: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. A. Moore: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. B.A. Hug: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline.
Resources from the same session
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract