729P - Adoptive T-cell therapy during chemotherapy with or without peginterferon-α (IFNα) in patients with platinum sensitive recurrent epithelial ovarian cancer (EOC)

Background

The correlation between T-cell infiltration and EOC survival suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL). Carboplatin-paclitaxel chemotherapy (CPC) lowers the number of tumor induced immune suppressive myeloid cells, creating a window-of-opportunity for TILs to exert their effective anti-tumor response. IFNα supports TIL. A phase I/II trial (NCT04072263) was initiated to study the feasibility and safety of TIL during CPC +/- IFNα in patients with recurrent platinum sensitive EOC.

Methods

Fourteen patients with recurrent platinum sensitive EOC received CPC iv q3weeks 6 times and TIL iv 2 weeks after the 2^nd, 3^rd and 4^th CPC cycle. IFNα was added in the second cohort for 12 weeks, starting one week before the first TIL infusion. Patients who received 3 TIL cycles were evaluable. The primary endpoint was feasibility and safety of TIL administration during CPC with or without IFNα. Secondary, signs of activity, its underlying mechanisms, immunomodulation, and T-cell reactivity were studied.

Results

Twelve patients were available for analysis. Median age 58 years (range, 29-75), 11 HGSOC and 1 LGMOC. TIL could be successfully expanded for all patients. Treatment with TIL during CPC was safe and did not add toxicity. Addition of IFNα resulted in grade 3 leucopenia and grade 3 trombocytopenia in the first 2 patients and was therefore omitted in subsequent patients. CPC alleviated the immunosupressive TME, reflected by reduced plasma IL-6 levels and circulating myeloid-cell numbers, with increased required lymphocytes and improved T-cell function, most prominently at 1-2 weeks after the 2^nd CPC. Objective responses were observed in 10/12 (83%) patients and 2 had stable disease. Interestingly, in at least one patient the ongoing platinum free interval (PFI) of 19 months far exceeds the first PFI of 8 months after similar CPC. In depth studies on immune modulation by chemotherapy and by TIL/IFNα, and correlations between TIL phenotype and clinical outcome are ongoing and will be presented at ESMO.

Conclusions

Combined treatment with CP chemotherapy and properly timed TIL may result in clinical benefit for patients with EOC.

Clinical trial identification

NCT04072263.

Editorial acknowledgement

Legal entity responsible for the study

Leiden University Medical Center.

Funding

OVACURE unrestricted grant.

Disclosure

All authors have declared no conflicts of interest.