An autologous Vγ9Vδ2 T lymphocytes cell therapy product generated by BrHPP (INNACELL Gamma Delta [IGD]) in metastatic renal cell carcinoma patients: Phase I clinical trial results

Abstract

2550 Background: Vγ9Vδ2 (γδ) T lymphocytes, a peripheral blood lymphocyte subset, have shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes γδ can be selectively expanded ex vivo with BrHPP (Phosphostim) and IL-2. We conducted a phase I trial, to define the dose limiting toxicities (DLT), characterize the safety profile, the pharmacodynamics and potential efficacy. Methods: Patients (pts), with progressive mRCC, PS of 0–1 and no organ dysfunction, were included. A one hour iv infusion of IGD was administered alone at cycle 1, and combined with low dose of sc IL-2 (2 MIU/m2 d1 to d7) in the 2 subsequent cycles (every 3 weeks). IGD dose was escalated from 1, up to 8 billions cells (bil). Results: 10 mRCC pts were treated in the study at 3 IGD dose levels: 1 patient at 1 bil, 6 pts at 4 bil, 3 pts at 8 bil. One patient experienced a grade (G)3 hypotension (4 bil, cycle 3), and one patient presented reversible signs of biological disseminated intravascular coagulation (8 bil, cycle 2) graded as a serious adverse event and fulfilling a DLT criteria. At all doses the treatment was well tolerated during the product alone infusion (cycle 1). The most frequent type of adverse events presented was mild to moderate flue like symptomes as fever, chills and asthenia reported during the second and third cycles in the IL-2 combined cycles. Patients presented also gastrointestinal symptoms as nausea and vomiting of grade 1 or 2. Preliminary efficacy assessment evaluation shows: 2 pts were not evaluable, 3 pts were withdrawn for disease progression at 3, 8 and 11 weeks, 2 pts maintained a stable disease for 36 and 63 weeks, and 2 pts are still under follow up with a stable disease at >91 and >124 weeks post treatment. Of note, one patient showed a 19% decrease in tumour size and another one presented a significant pain decrease leading to quality of life improvement. One other patient recently treated, is still under follow-up without progression after >16 weeks post treatment. Conclusion: IGD in combination with sc low dose IL-2 is safe, well tolerated, and shows promising antitumor signs of efficacy. These results warrant further product evaluation in phase 2 clinical trials. [Table: see text]