Early data from a first-in-human study of affinity-enhanced autologous SPEAR T cells (AFPc332) directed towards the HLA-A*02-restricted AFP peptide FMNKFIYEI showed no on-target or off-target toxicity in 2 patients with hepatocellular carcinoma, according to the results presented at the American Association of Cancer Research (AACR) Annual Meeting 2019.

In addition, no protocol defined dose-limiting toxicities have occurred, supporting the continued investigation of AFPc332 T cells.

To qualify for the study, patients have to have hepatocellular carcinoma, and:

  • be ineligible for transplant, resection, or locoregional therapy
  • have failed, be intolerant to, or refused standard of care treatment
  • be HLA-A*02:01 positive of 02:642 positive
  • have AFP expression by immunohistochemistry at ≥1+ in ≥20% HCC tumor cells or serum AFP ≥400 ng/ml and ≤5% IHC AFP in non-cancerous liver tissue

Researchers plan to enroll up to 24 patients. Data presented were from the first 2 patients treated with AFP SPEAR T cells.

Patients received lymphodepletion with fludarabine 20 mg/m2 per day and cyclophosphamide 500 mg/m2 per day on days -7 and -5. Initial transduced cell dose is 0.1 x 109 with additional doses at 1 x 109 and 5 x 109.

Both patients had cytopenias related to the lymphodepleting therapy. However, no cytokine release syndrome or serious adverse events occurred during their initial hospitalization. AFPc332 T cells were detected in both patients.

In the first patient, posttreatment imaging showed stable disease at week 12. The patient had a grade 1 cognitive disturbance on day 8, serious adverse events of biliary obstruction at week 9 treated by stenting, and abdominal pain at week 12. A biopsy of the tumor at week 8 showed diffuse tissue necrosis with cholestasis suspicious for necrotic tumor cells.

To date, no serious adverse events have been reported in the second patient, and posttreatment imaging is pending.

Reference

  1. Goyal L, Frigault M, Meyer T, et al. Initial safety of AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract 3183/6.