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517 Background: ADP-A2M4CD8 is a specific peptide enhanced affinity receptor mixed CD4+ and CD8+ T-cell therapy targeting the cancer testis antigen MAGE-A4 and modified with addition of a CD8α co-receptor designed to provide additional functionality to CD4+ T-cells. ADP-A2M4CD8 has demonstrated an acceptable benefit to risk profile in the Phase 1 SURPASS trial (NCT04044859) in HLA A*02–eligible patients with unresectable or metastatic tumors positive for MAGE-A4.1 Here we report updated clinical outcomes in patients with urothelial cancer (UC). Methods: SURPASS is a first-in-human trial consisting of a modified 3+3 dose-escalation design and an expansion cohort. Autologous T-cells are obtained by leukapheresis, transduced with a self-inactivating lentiviral vector expressing the MAGE-A4-specific T-cell receptor and the CD8α co-receptor, and infused back to the patients as ADP-A2M4CD8 following lymphodepleting chemotherapy. Primary and secondary objectives are safety and anti-tumor activity, respectively. Results: At ESMO 2022, we reported promising results from SURPASS in several tumour types.2 In the 43 evaluable patients, the overall response rate was 28%, including 1 complete response and 11 partial responses (PR), and an additional 2 unconfirmed PRs awaiting confirmatory scans (as of August 1, 2022). Data from the 7 evaluable patients in the UC subset (updated September 6, 2022) showed that 3 (43%) had a best overall response of PR, and 1 (14%) had an unconfirmed PR. Disease control rate was 100% (3 PR + 1 unconfirmed PR + 3 stable disease). Adverse events have been consistent with those typically observed with lymphodepletion chemotherapy or cellular therapy. This trial is ongoing; data from additional patients with UC treated by January 2023 and updated translational data will be presented. Conclusions: ADP-A2M4CD8 continues to show an acceptable benefit to risk profile in multiple MAGE-A4+ unresectable or metastatic tumors, and preliminary encouraging evidence of efficacy in UC. An additional treatment cohort has been included in the updated trial protocol to evaluate ADP-A2M4CD8 combined with nivolumab. 1. Hong DS, et al. E-poster 540P: ESMO 2021; Virtual. 2. Hong DS, et al. Ann Oncol 33(suppl_7); S331-S355, Abstract 735MO. ESMO 2022. Clinical trial information: NCT04044859 .

349 Background: ADP-A2M4CD8 is a specific peptide enhanced affinity receptor mixed CD4+ and CD8+ T-cell therapy targeting the cancer testis antigen MAGE-A4 and modified with addition of a CD8α co-receptor designed to provide additional functionality to CD4+ T-cells. ADP-A2M4CD8 has demonstrated a favorable benefit to risk profile in the Phase 1 SURPASS trial (NCT04044859) in HLA A*02–eligible patients (pts) with unresectable or metastatic tumors positive for MAGE-A4 (Hong DS, et al. E-poster 540P: ESMO 2021; Virtual). Here we report updated clinical outcomes in pts with esophageal, esophagogastric junction (EGJ), or gastric cancer. Methods: SURPASS is a first-in-human trial consisting of a modified 3+3 dose-escalation design and an expansion cohort. Autologous T-cells are obtained by leukapheresis, transduced with a self-inactivating lentiviral vector expressing the MAGE-A4-specific T-cell receptor and the CD8α co-receptor, and infused back to the pts as ADP-A2M4CD8 following lymphodepleting chemotherapy. Primary and secondary objectives are safety and anti-tumor activity, respectively. Results: As September 6, 2022, 13 pts (11 male, 2 female) with esophageal (3), EGJ (8), and gastric cancer (2) received ADP-A2M4CD8 (range: 1.02–9.9x109 transduced T-cells). All pts had adenocarcinoma, median age was 55 years (range: 31–71), median MAGE-A4 expression H-score was 245 (range: 160–300), and pts received median of 2 lines of prior therapy (range 1–5). Adverse events (AEs) were consistent with those typically associated with lymphodepleting chemotherapy, cellular therapy, and/or disease. One pt had a Grade 5 (fatal) AE of pancytopenia. Overall response rate per RECIST v1.1 by investigator review was 15% (2 partial response [PR]). Disease control rate was 77% (2 PR+8 stable disease). This trial is ongoing, and additional data will be presented. Conclusions: Results indicate an acceptable benefit to risk profile and encouraging anti-tumor activity of ADP-A2M4CD8. An additional treatment cohort has been included in the updated SURPASS trial protocol to evaluate ADP-A2M4CD8 combined with nivolumab. A Phase 2, open-label trial in advanced esophageal and EGJ cancers has been initiated (SURPASS-2; NCT04752358). Clinical trial information: NCT04044859 .

e24138 Background: Distress has a negative impact on the patient experience of cancer. We previously demonstrated that patients with metastatic non-small cell lung cancer (mNSCLC) face significant and sustained distress during first-line treatment. However, the association between distress and unplanned healthcare utilization (HCRU) is not well understood. Here we examine this association. Methods: We conducted secondary analyses of data from 152 adult patients with mNSCLC treated at Duke Cancer Institute who were part of a retrospective chart review study (3/15-6/20). For the original investigation, demographic, clinical, and distress data were abstracted. NCCN Distress Thermometer (DT) scores were recorded at each clinic visit from start of first-line therapy to end of first year, change in therapy or death. The DT is an 11-point ordinal scale, with a 39-item Problem List, assessing overall distress. DT scores of > = 4 indicate actionable distress. Further HCRU data were analyzed, including unplanned hospitalizations, 30-day readmissions, length of stay, clinic visits, infusion center visits, emergency department (ED) visits, and death. Descriptive statistical analyses were performed for sources of distress and HCRU. To examine the association between distress and HCRU, we utilized an adjusted frailty model (for baseline demographics, metastatic site, and National Cancer Institute Index). This Cox proportional hazards model allowed for multiple HCRU events per patient and included actionable distress as a time-dependent covariate. Results: First, the proportion of actionable DT scores (423/1652, 25.6%) was strikingly high. Most DTs included report of at least one physical problem (n = 1593, 96.4%), regardless of distress level. However, emotional problems (e.g., worry, nervousness, depression) were reported much more frequently when the DT score was actionable (61.9% vs. 20.8%). At the patient level (n = 152), actionable distress was associated with increased HCRU. For example, a larger proportion of those with an average DT score > = 4 had at least one hospitalization (n = 22, 53.7%), infusion center visit (n = 11, 26.8%) or ED visit (n = 28, 68.3%) compared to patients with a non-actionable average DT score. Furthermore, HCRU was 54% more likely to occur after a patient reporting actionable distress compared to a patient reporting lower distress levels any time during treatment (adjusted HR 1.54; CI 1.20, 1.97). A one-point increase in distress was associated with an 8% increase in risk of HCRU (HR 1.08; CI 1.03, 1.13) at any point during treatment. Conclusions: Patients with mNSCLC experience high levels of distress, with actionable distress appearing to be driven significantly by emotional problems. Patient-reported distress is also associated with HCRU. Intervention development and testing is needed to address the unmet psychological needs in lung cancer care and their potential impact on unplanned HCRU.