6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study

Background

NY-ESO-1 and LAGE-1a are antigens expressed in several tumours, including non-small cell lung cancer (NSCLC). Previous clinical trials using autologous T cells directed against NY-ESO-1/LAGE-1a have shown objective responses between 40% and 60% in synovial sarcoma, metastatic melanoma and multiple myeloma. Pembrolizumab (PEM) is a monoclonal antibody that blocks PD-1/PD-L1 interaction and increases anti-tumour activity in anti-tumour T cells. Here, PEM will be used in combination with NY-ESO-1/LAGE-1a T-cell receptor engineered patient T cells (GSK3377794) to potentially improve clinical benefit in this patient population.

Trial design

This is a phase Ib/IIa, randomised, multi-arm, open-label study (NCT03709706) of GSK3377794 in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive adults with NY-ESO-1 and/or LAGE-1a-expressing tumours. Eligible patients with unresectable Stage IIIb/IV NSCLC are either ineligible for standard-of-care chemoradiotherapy, have received PD-1 therapy or appropriate targeted therapy, have terminated prior treatment due to intolerable side effects, or have refused standard approved treatment. At least 30 patients with NSCLC without EGFR or ALK/ROS1 aberrations will be randomised (1:1) to Arm A or B; at least 15 patients with EGFR or ALK/ROS1 aberration will be assigned to Arm C. Patients in Arm A will receive a single IV infusion of GSK3377794; those in Arms B and C will receive GSK3377794 IV on Day 1, then PEM 200 mg starting on Day 22 and continuing for up to 35 cycles or disease progression. Patients in Arm A who progress within 25 weeks post GSK3377794 infusion may receive PEM at the same dose/duration as Arms B and C. The study will have 3 parts: eligibility screening (Part 1); leukapheresis and manufacture of GSK3377794 (Part 2); lymphodepletion and infusion of GSK3377794 (interventional phase; Part 3). Primary objectives are to assess the safety and tolerability of GSK3377794 alone or in combination with PEM and to determine the clinical response. The first patient was screened on December 31, 2018.

Clinical trial identification

NCT03709706.

Editorial acknowledgement

Fiona Woodward, PhD, and Leigh O’Connor-Jones, PhD, of Fishawack Indicia Ltd, UK, funded by GlaxoSmithKline (GSK).

Legal entity responsible for the study

GSK in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

GlaxoSmithKline.

Disclosure

K.L. Reckamp: Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Acea; Research grant / Funding (institution): Adaptimmune; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy: Genentech; Research grant / Funding (institution): GSK; Honoraria (self), Advisory / Consultancy: Guardant; Research grant / Funding (institution): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Loxo Oncology; Research grant / Funding (institution): Molecular Partners; Research grant / Funding (institution): Xcovery; Research grant / Funding (institution): Zeno; Honoraria (self), Advisory / Consultancy: Precision Health; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Tesaro. W. Akerley: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Takeda. E. Calvo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Project lead: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Nanobiotix; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: GLG; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Non-remunerated activity/ies: PsiOxus Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Medscape; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Cerulean Pharma; Honoraria (self), Advisory / Consultancy: EUSA; Honoraria (self), Advisory / Consultancy: Gehrmann Consulting; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Project lead: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Guidepoint; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amcure; Honoraria (self), Advisory / Consultancy: OncoDNA; Honoraria (self), Advisory / Consultancy: Alkermes; Leadership role, Full / Part-time employment, Director, Clinical Research; employed as medical oncologist: START Madrid; Leadership role, Full / Part-time employment, Director, Clinical Research; employed as medical oncologist: HM Hospitals Group; Leadership role, Co-director: Methods in Clinical Cancer Research (MCCR) ; Leadership role, Founder and president, non-for-profit Foundation: INTHEOS; Shareholder / Stockholder / Stock options: START Madrid; Shareholder / Stockholder / Stock options: Oncoart Associated; Shareholder / Stockholder / Stock options: International Cancer Consultants; Research grant / Funding (institution): ACEO; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Cytomx; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): H3; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Kura; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Menarini; Research grant / Funding (institution): Merus; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Principia; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution), Project lead: BeiGene; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Innovio; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Daiichi; Research grant / Funding (institution): ORCA; Research grant / Funding (institution): Boston Therapeutics; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): DebioPharm; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Millenium; Research grant / Funding (institution): Synthon; Research grant / Funding (institution): Spectrum; Research grant / Funding (institution): Rigonetec; Non-remunerated activity/ies, Membership: SEOM; Non-remunerated activity/ies, Membership: EORTC; Leadership role, Membership, non-remunerated: ESMO; Leadership role, Membership, non-remunerated: ASCO. J. Clarke: Research grant / Funding (institution), Research Grant Principle Investigator: Medpacto; Advisory / Consultancy, Research grant / Funding (institution), Principle Investigator: Eli Lilly; Research grant / Funding (institution), Principle Investigator: Bristol-Myers Squibb; Research grant / Funding (institution), Principle Investigator: Genentech; Research grant / Funding (institution), Principle Investigator: Spectrum; Research grant / Funding (institution), Principle Investigator: Adaptimmune; Research grant / Funding (institution), Principle Investigator: Bayer; Research grant / Funding (institution), Principle Investigator: AbbVie; Research grant / Funding (institution), Principle Investigator: Moderna; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant; Honoraria (self), Advisory / Consultancy: AstraZeneca. M.J. Edelman: Advisory / Consultancy, Advisor/board member: WindMIL Therapeutics; Advisory / Consultancy, Consultant/Independent Contractor: Armo; Advisory / Consultancy, Consultant/Independent Contractor: BerGen Bio; Advisory / Consultancy, Consultant/Independent Contractor: Syndax; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Takeda; Shareholder / Stockholder / Stock options: Biomarker Strategies. K. He: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory Board: BMS; Advisory / Consultancy, Consultant: Consultant/Independent Contractor; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Geneplus; Research grant / Funding (institution): Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Mirati; Research grant / Funding (institution), Travel / Accommodation / Expenses: GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses: Adaptimmune. J.W. Neal: Advisory / Consultancy, Research grant / Funding (institution): ARIAD/Takeda; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Jounce Therapeutics; Advisory / Consultancy: Lilly; Advisory / Consultancy: Loxo Oncology; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Novartis. S.P. Patel: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Illumina; Advisory / Consultancy: Novartis; Advisory / Consultancy: Tempus; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Fate Therapeutics; Research grant / Funding (institution): Genocea; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Xcovery. J.W. Riess: Advisory / Consultancy, Consultant: Celgene; Advisory / Consultancy, Advisor / board member: Heron; Advisory / Consultancy, Advisor / board member: Loxo; Advisory / Consultancy, Advisor / board member: Boehringer Ingelheim; Research grant / Funding (institution): Spectrum; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. A.G. Sacher: Advisory / Consultancy, Advisory Board Member: Bayer; Honoraria (self): Bayer; Honoraria (self): AstraZeneca; Honoraria (self): Genentech-Roche; Honoraria (self): Merck. S. Turcotte: Advisory / Consultancy: TVM Life Sciences Management Inc.; Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): AstraZeneca; Honoraria (self): Exactis Innovation. L.C. Villaruz: Advisory / Consultancy, Research grant / Funding (institution), Advisor/board member: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merck. M.G. Zauderer: Officer / Board of Directors, Non-remunerated activity/ies: Mesothelioma Applied Research Foundation; Advisory / Consultancy, Independent contractor: Aldeyra; Advisory / Consultancy, Research grant / Funding (institution), Independent contractor: Epizyme; Full / Part-time employment, Employee of MSK which receives royalties from IBM (collaboration on Watson for Oncology tool): MSK; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Sellas Life Sciences; Research grant / Funding (institution): Millenium; Research grant / Funding (institution): Curis. B. Farsaci: Shareholder / Stockholder / Stock options, Full / Part-time employment: GSK. N. Skoura: Shareholder / Stockholder / Stock options, Full / Part-time employment: GSK. M. Chisamore: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme, Corp., a subsidiary Merck & Co., Inc., Kenilworth, NJ, USA. M.L. Johnson: Honoraria (institution), Advisory / Consultancy: Araxes Pharma; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Calithera; Honoraria (institution), Advisory / Consultancy: Genentech/Roche; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Guardant Health; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Incyte; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Loxo Oncology; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (institution), Advisory / Consultancy: Mersana Therapeutics; Honoraria (institution), Advisory / Consultancy: Mirati; Honoraria (institution), Advisory / Consultancy: Ribon Therapeutics; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Honoraria (institution), Advisory / Consultancy: Otsuka Pharmaceuticals; Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Daiichi Sankyo; Travel / Accommodation / Expenses: Exelixis; Travel / Accommodation / Expenses: Sysmex Inostics; Travel / Accommodation / Expenses: Vapotherm; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Acerta; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Apexigen; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Birdie; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Corvus; Research grant / Funding (institution): Cytomx; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Genocea; Research grant / Funding (institution): Gritstone; Research grant / Funding (institution): Hengrui Therapeutics, Inc.; Research grant / Funding (institution): Kadmon; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): Neovia; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Tarveda. All other authors have declared no conflicts of interest.