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*02–eligible 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: 31–75) mainly with melanoma, non-small cell lung, ovarian, gastroesophageal, head and neck, or urothelial cancers received 1.02–9.95x109 ADP-A2M4CD8 T-cells. Median (range) number of prior lines of therapy was 3 (1–8) and MAGE-A4 expression H-score was 250 (90–300). 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.
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