Adaptimmune Therapeutics plc announced updated data from its Phase 1 SURPASS trial in multiple solid tumors to be presented in a digital poster at the upcoming European Society for Medical Oncology (ESMO) annual meeting. Topline results from the Phase 1 SURPASS trial (data cut-off August 2, 2021): Emerging efficacy and durability data are promising with responses in five solid tumor indications. As of the data cut-off date, 25 patients had received the next-generation cell therapy, ADP-A2M4CD8, in the Phase 1 SURPASS trial, 22 patients were evaluable for efficacy with at least one post-baseline scan meeting the =4-week duration for evaluation of stable disease. All patients had advanced metastatic disease and had received multiple prior regimens of systemic therapy (median: 3; range 1-6). The overall response rate was 36% and the disease control rate was 86%. There was a complete response reported in a patient with ovarian cancer, which remains ongoing at 6 months post-infusion (data on file at Adaptimmune). Initial durability is encouraging. As of the data cut-off, 11 patients remain on study. Of the 8 responders, 5 remain in response with some remaining progression free >24 weeks. ADP-A2M4CD8 demonstrated an acceptable safety profile: Eighteen (72%) patients experienced cytokine release syndrome (CRS) related to T-cell infusion, most of which were lower grade: Grade 1 or 2 (n=14); Grade 3 (n=4). The most common serious adverse event (SAE) of any grade (> 30% of patients) was CRS. Four (16%) patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) related to T-cell infusion: Grade 1 (n=1); Grade 2 (n=1); Grade 3 (n=2). Five (20%) patients experienced prolonged cytopenia at Week 4. One patient experienced a fatal (Grade 5) SAE of pancytopenia. ADP-A2M4CD8 was designed to be more potent than the first-generation product. Adaptimmune’s Specific Peptide Enhanced Affinity Receptor (SPEAR) T-cell therapies are a mix of CD8+ (“killer”) and CD4+ (“helper”) T-cells engineered with a T-cell receptor (TCR) designed with Adaptimmune’s proprietary affinity enhancement technology to recognize a cancer target. ADP-A2M4CD8 is a next-generation T-cell therapy engineered to target MAGE-A4 positive tumors, and to express a CD8a co-receptor. ADP-A2M4CD8 uses the same engineered T-cell receptor that recognizes MAGE-A4 as Adaptimmune’s first-generation T-cell therapy, afami-cel, which has shown compelling results in synovial sarcoma and myxoid/round cell liposarcoma (presented at ASCO 2021). Co-expression of CD8a adds CD8+ killer cell capability to CD4+ helper T-cells, while maintaining or enhancing the CD4+ helper function (i.e., producing the inflammatory cytokines IFN-? and IL-2). Initial translational data confirm that ADP-A2M4D8 is more potent and better engages the immune system, compared to the first-generation product: Patient manufactured product and serum samples from the first-generation Phase 1 afami-cel trial and the next-generation SURPASS trial were compared. In vitro tumor cell killing assays confirm that the next-generation product results in greater tumor cell killing by CD4+ SPEAR T-cells. Analyses of patient serum samples demonstrate increases in a subset of 22 measured serum cytokines confirming increased helper function of the next-generation CD4+ T-cells and engagement of the broader immune system. Additional serum analyses showed increased serum IL-12 in the SURPASS trial versus the first-generation Phase 1 trial, which is also consistent with engagement of the broader immune system, including dendritic cells, as IL-12 is not known to be produced by T-cells. Conclusions from the Phase 1 SURPASS Trial Data at ESMO: Initial efficacy and durability data are encouraging with responses across five different solid tumors including a complete response in a patient with ovarian cancer ongoing at 6 months. The safety profile of the next-generation ADP-A2M4CD8 cell therapy was acceptable. Data confirm preclinical observations that the enhanced TCR interaction in ADP-A2M4CD8 results in a more potent product. Safety and efficacy, including duration of response, will continue to be evaluated in the ongoing SURPASS trial, which is enrolling eligible patients with gastroesophageal, head and neck, lung, bladder, and ovarian cancers. A Phase 2 trial, SURPASS-2, has initiated for patients with esophageal and EGJ cancers. Overview of Phase 1 SURPASS trial design: This is a Phase 1, open-label, dose escalation clinical trial designed to evaluate the safety and antitumor activity of ADP-A2M4CD8 in patients with MAGE-A4+ tumors in the context of HLA-A*02. This is a first-in-human dose-escalation trial using a modified 3+3 design, with 2 dose cohorts plus an expansion cohort. The number of transduced cells ranged from 0.8x109 to 1.2x109 (Cohort 1 complete), 1.2x109 to 6.0x109 (Cohort 2 complete), and 1.2x109 to 10.0x109 (Expansion). Dose-limiting toxicities are adjudicated by a Safety Review Committee, regardless of the investigator’s attribution. Responses are assessed per RECIST v1.1.