subslover
11 months ago
Adaptimmune Announces U.S. FDA Acceptance of Biologics License Application for Afami-cel for the Treatment of Advanced Synovial Sarcoma with Priority Review
Newsfile Corp.
Newsfile Corp
If approved, afami-cel will be the first engineered T-cell therapy for solid tumors and the first effective treatment option for synovial sarcoma in more than a decade
Philadelphia, Pennsylvania and Oxford, United Kingdom--(Newsfile Corp. - January 31, 2024) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review its Biologics License Application (BLA) for afami-cel, an investigational engineered T-cell therapy for advanced synovial sarcoma. The application has a Prescription Drug User Fee Act (PDUFA) target action date of August 4, 2024.
Adrian Rawcliffe, Adaptimmune's Chief Executive Officer: βThe FDAβs acceptance of the BLA submission brings us one step closer to redefining treatment for people with synovial sarcoma. Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel - the first engineered T-cell therapy on the market for a solid tumor cancer.β
Dennis Williams, PharmD, Senior VP of Late-Stage Development: "Historic outcomes are poor for advanced synovial sarcoma, with low objective response rates for second-line therapies and overall survival of less than 12 months for people who have received two or more prior lines of therapy. In clinical trials, afami-cel has demonstrated an impressive response rate of ~39% among heavily pre-treated patients with advanced synovial sarcoma and about a 17-month median survival. This regulatory milestone is a testament to our teams' relentless work to deliver a novel treatment option to more people diagnosed with synovial sarcoma."
This acceptance is supported by positive data from Cohort 1 of the pivotal trial SPEARHEAD-1, which met its primary endpoint for efficacy. Data from the trial were presented at the Connective Tissue Oncology Society (CTOS) 2023 Annual Meeting.
jondoeuk
11 months ago
Hard to say, but they have only talked about sequential/combination treatment with afami-cel and lete-cel, not committed to it. Based on what others are doing, I would like them to pick up the pass of innovation. Based on their own data, a TGF-B signature was measured across tumour indications, so think they should test the combination of NY-ESO-1 with MAGE-A4 TCRs that co-express the CD8a co-receptor with a dnTGF-BRII as well. They also ran a sub-study testing afami-cel with low-dose radiation. While small, it did show greater detection of SPEAR T-cells in tumour biopsies when infusion followed it. As for TC-520 (targeting CD70), I think it should be dropped.
jondoeuk
1 year ago
Hard to say, but in the next few I expect to see datasets from others trials (testing ADCs) in platinum-resistant ovarian. However, there are downsides including, TEAEs, such as those leading to drug discontinuation, interruption or reduction. Also, dosing every 'x' amount of weeks.
jondoeuk
1 year ago
The ESMO abstract
1019O - Clinical and translational data from the phase I SURPASS trial of ADP-A2M4CD8 T cell receptor (TCR) T cell therapy alone or combined with nivolumab in solid tumors
Background
ADP-A2M4CD8 is a TCR T-cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), modified with a CD8a coreceptor, to treat human leukocyte antigen A*02βeligible patients (pts) with unresectable/metastatic solid tumors. ADP-A2M4CD8 monotherapy has demonstrated an acceptable benefit-to-risk profile and encouraging anti-tumor activity in the ongoing phase 1 SURPASS trial. Nevertheless, inhibition of immunosuppressive pathways may improve anti-tumor responses; therefore, new SURPASS cohorts include ADP-A2M4CD8 combined with nivolumab or pembrolizumab. We report data from pts receiving monotherapy and nivolumab combination therapy.
Methods
T-cells are obtained by leukapheresis, transduced with a lentiviral vector carrying the TCR and CD8a coreceptor genes, expanded ex vivo, and infused back to the pt following lymphodepleting chemotherapy. ~Four weeks after ADP-A2M4CD8 infusion, a subset of pts also received nivolumab 480 mg every 4 weeks until unacceptable toxicity/disease progression. Primary and secondary objectives are safety and anti-tumor activity, respectively.
Results
As of March 9, 2023, 51 pts with a median age of 60 years (range: 31β75) mainly with melanoma, non-small cell lung, ovarian, gastroesophageal, head and neck, or urothelial cancers received 1.02β9.95x109 ADP-A2M4CD8 T-cells. Median (range) number of prior lines of therapy was 3 (1β8) and MAGE-A4 expression H-score was 250 (90β300). The four most common adverse events related to T-cell therapy were cytokine release syndrome (n=38 [74.5%]; 7 [13.7%] were Grade≥3), neutropenia (27.5%), pyrexia and fatigue (each 21.6%). Overall response rate per RECIST v1.1 by investigator review in monotherapy pts (n=45) was 35.6% (2 complete response, 14 partial response [PR]). Median duration of response was 20.79 weeks (95%CI: 11.6, 30.9). In pts assigned to nivolumab combination (n=6), there was 1 PR, 3 stable disease, and 2 not evaluable (2 pts have not received nivolumab and have no post-baseline RECIST assessment). Data from additional pts treated by August 2023 will be presented.
Conclusions
ADP-A2M4CD8 continues to show an acceptable benefit-to-risk profile, including in pts receiving nivolumab combination therapy.