dm+d

Unassigned

New Medicines

NY-ESO-1 and/or LAGE-1a-positive solid tumours

Information

New molecular entity
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Nov 17Adaptimmune announces that, with GSK exercising its option over NY-ESO programme, the planned pivotal registration trial of letetresgene autoleucel in synovial sarcoma, will transition to GSK [3].
Jul 16EMA grants Priority Medicine (PRIME) statusl for the treatment of HLA-A*201, HLA-A*205, or HLA-A*206 allele positive patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumour expresses the NY-ESO-1 tumour antigen [3].
Jul 16Granted orphan drug status in EU for synovial sarcoma (soft tissue sarcoma). Previously also awarded in the US [3].
Feb 16FDA grants breakthrough therapy status for letetresgene autoleucel in synovial sarcoma for HLA-A*201, HLA-A*205 or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma who received prior chemotherapy and whose tumour expressed the NY-ESO-1 tumour antigen. The designation was based on the results of the PI/II trial (NCT01343043) in patients with unresectable, metastatic or recurrent synovial sarcoma and previously treated with chemotherapy [3].

Category

An affinity enhanced T-cell immunotherapy based on Adaptimmune SPEAR T-cells (Specific Peptide Enhanced Affinity Receptor T-cells), targets NY-ESO-1 or LAGE-1a antigenic peptides & HLA-A2. Autologous polyclonal T cells transduced by a lentiviral vector
Variable depending on tumour type. CTAs, NY-ESO-1 and LAGE-1A, are expressed on tumour cells. Expression frequency of NY-ESO-1 differs greatly with the most commonly expressing tumours being myxoid and round cell liposarcoma (89–100%), neuroblastoma (82%), synovial sarcoma (80%), melanoma (46%), and ovarian cancer (43%) [1].
NY-ESO-1 and/or LAGE-1a-positive solid tumours
Intravenous infusion

Trial or other data

Nov 21PII IGNYTE-ESO trial is recruiting; timescales unchanged [4].
Nov 20PII IGNYTE-ESO trial is recruiting. It uses a master protocol consisting of a core protocol with multiple independent substudies, investigating GSK3377794 treatment in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced metastatic or unresectable synovial sarcoma (Substudy 1) and GSK3377794 as second line or higher (2L+) treatment HLA-A*02+ participants with NY-ESO-1+ advanced metastatic or unresectable synovial sarcoma who have progressed following treatment with anthracycline based chemotherapy (Substudy 2). (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumour types [2].
Dec 19PII IGNYTE-ESO trial to evaluate the efficacy of affinity letetresgene autoleucel in synovial sarcoma starts (NCT03967223; 208467). 65 patients aged 10 years and older will be recruited in the UK (Manchester and London - exact sites not stated), Canada, France, Germany, the Netherlands, Spain and the US. Primary outcome is overall response rate up to 5 years; collection of these data is due to complete Nov 22 [2].
Jun 18In a PI/II trial (NCT02992743) being conducted in patients with myxoid/ round cell liposarcoma (MRCLS), four patients were reported to have partial responses (three confirmed and one to be confirmed) and one stable disease was reported. There was tumour burden decrease in majority of patients across target lesions ranged from 16.9% to 50%. Updated data from the trial showed that out of ten MRCLS patients, four partial responses (three confirmed and one to be confirmed) and four stable diseases were reported. Overall, there was a reduction in target lesions in seven out of eight evaluable patients [3].