Introduction/Background ADP-A2M4CD8, an autologous mixed CD4+ and CD8+ T-cell receptor (TCR) T-cell therapy, targets melanoma-associated antigen A4 (MAGE-A4) in an HLA-A*02 restricted manner and expresses a CD8α co-receptor conferring additional functionality. MAGE-A4 is expressed (≥30% tumour cells at ≥2+ intensity by immunohistochemistry) in ~25% of ovarian cancers, and ~45% of the US/European population express the relevant HLA-A*02 alleles. The ongoing Phase 1 SURPASS trial (NCT04044859) of ADP-A2M4CD8 in HLA-A*02-eligible participants demonstrated an acceptable benefit to risk profile with responses across multiple MAGE-A4+ solid tumours, including platinum-resistant ovarian cancer, with an overall response rate on 09 March 2023 of 40% (6/15).

Methodology Consequently, an open-label, non-comparative Phase 2 trial (SURPASS-3; NCT05601752; partnered with GOG Foundation, GOG-3084) will investigate ADP-A2M4CD8 for ovarian cancer, including a combination cohort with nivolumab exploring the potential to increase ADP-A2M4CD8 efficacy by overcoming immunosuppressive pathways.

Results Approximately 66 participants, aged 18–75 years, will be randomised 1:1 to receive ADP-A2M4CD8 or ADP-A2M4CD8/nivolumab. Key eligibility criteria: histologically confirmed high-grade serous or endometrioid recurrent/progressive ovarian carcinoma; ≥3 cycles of prior platinum-/taxane-based chemotherapy; measurable disease per RECIST v1.1; MAGE-A4 expression; HLA-A*02:01P, 02:02P, 02:03P, or 02:06P but no HLA-A*02:05P alleles; and ECOG performance status of 0 or 1. Autologous T-cells will be collected by leukapheresis and transduced with a lentiviral vector. Lymphodepletion chemotherapy (fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days) will be followed by infusion of 1–10x10^9 ADP-A2M4CD8 T-cells. From Week 4 post-infusion, combination arm participants will receive nivolumab 480 mg every 4 weeks. Imaging will be performed at baseline, Weeks 8, 16, 24, then every 2 months ± 28 days until disease progression. Primary endpoint is objective response per RECIST v1.1 by independent review. Adverse events will be monitored, with participants followed for 15 years from T-cell infusion.

Conclusion SURPASS-3 is initiating in Q2 2023.

Disclosures The authors would like to acknowledge Jose Saro, Stavros Rafail, and Robert Connacher of/formerly of Adaptimmune for their contributions to SURPASS-3 trial design. This study was sponsored by Adaptimmune. Writing/editorial support was provided by Christine Ingleby, DPhil, CMPP, of Excel Scientific Solutions and was funded by Adaptimmune.