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.
- 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.