On November 29, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported the transfer of the IND for letetresgene autoluecel (lete-cel) from GSK to Adaptimmune for the pivotal IGNYTE-ESO (NCT03967223) clinical trial (Press release, Adaptimmune, NOV 29, 2023, View Source [SID1234638053]).
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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "The compelling clinical data from the pivotal IGNYTE-ESO trial frames lete-cel as the ideal synergistic product to afami-cel and could enable our sarcoma franchise to more than double the addressable patient population. Further, we can deliver lete-cel to market efficiently using the same commercial footprint we intend to use for afami-cel."
Adaptimmune recently reported data from a protocol-defined interim analysis of the pivotal IGNYTE-ESO trial. In this analysis, 40% (18/45) of people with synovial sarcoma or myxoid/ round cell liposarcoma (MRCLS) had confirmed clinical responses with lete-cel by independent review. The primary efficacy endpoint requires 16/60 patients have responses. As a result, the Company is evaluating the integration of lete-cel into its sarcoma franchise and is looking forward to sharing its development plans for lete-cel in the new year.
Lete-cel, an engineered TCR T-cell therapy targeting the solid tumor antigen NY-ESO-1, was originally developed by Adaptimmune, and further developed under a collaboration and license agreement with GSK plc. Lete-cel is being investigated for the treatment of synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) in the pivotal IGNYTE-ESO (NCT03967223) trial in patients who received prior anthracycline treatment. In 2023, Adaptimmune and GSK agreed terms regarding the return of the NY-ESO program back to Adaptimmune. Per the terms of the Agreement, Adaptimmune has received an upfront amount and will receive milestone-based payments totaling £30 million in relation to the transfer of the clinical trials for the NY-ESO targeted programs.
About synovial sarcoma
There are approximately 50 types of soft tissue sarcomas which are categorized by tumors that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.1 Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas (there are approximately 13,400 new soft tissue cases in the U.S. each year).2 One third of patients with synovial sarcoma will be diagnosed under the age of 30.2 The five-year survival rate for people with metastatic disease is just 20% and most people undergoing standard of care treatment for advanced disease experience recurrence and go through multiple lines of therapy, often exhausting all options.3
1. View Source accessed Oct. 24, 2023
2. Synovial Sarcoma – NCI (cancer.gov) accessed Oct. 24, 2023
3. Aytekin MN, et al. J Orthop Surg (Hong Kong). 2020;28(2)
About Myxoid/round cell liposarcoma (MRCLS)
Myxoid/round cell liposarcoma (MRCLS) is a type of soft tissue sarcoma that is predominantly found in the limbs. MRCLS accounts for approximately 5% to 10% of all soft tissue sarcomas.1 One-third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations. MRCLS commonly presents at an age ranging from 35-55 years and has a poor prognosis because it recurs locally and tends to metastasize quickly and widely. The 5-year survival rate for metastatic MRCLS is only 5%.2
1. View Source accessed Oct. 24, 2023
2. https: www.orpha.net accessed Oct. 24, 2023
Overview of IGNYTE-ESO trial design
IGNYTE-ESO is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of lete-cel. Lete-cel’s engineered TCR T-cells target NY-ESO-1+ tumors. NY-ESO-1 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.
Key eligibility criteria include ECOG performance status of 0 or 1; HLA*02 positive with confirmed NY-ESO expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 10 years; and patients must have measurable disease according to RECIST v1.1 at the time of treatment. The IGNYTE-ESO master protocol include two substudies – Substudy 1 was designed to investigate lete-cel in previously untreated advanced (metastatic or unresectable) synovial sarcoma or MRCLS; and Substudy 2 was designed to investigate lete-cel in advanced (metastatic or unresectable) synovial sarcoma or MRCLS post-anthracycline chemotherapy. Eligible patients received lete-cel doses between 1-15 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.
Approximately 10 people were planned to be treated in Substudy 1, 5 patients were treated and enrollment was stopped. Approximately 60 people were planned to be treated in Substudy 2 and enrollment is complete.