A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma.

Abstract

11 Background: Ilixadencel is a cell-based allogeneic off-the-shelf product aimed to prime anti-cancer immune response when injected intratumorally. The present randomized Phase II multicenter trial (MERECA; NCT02432846) evaluated intratumoral ilixadencel administration (2 doses 2 weeks apart) pre-nephrectomy followed by sunitinib post-nephrectomy compared with sunitinib monotherapy post-nephrectomy as first-line systemic therapy in patients with newly diagnosed synchronous metastatic renal cell carcinoma (mRCC). Methods: Patients were randomly assigned at two-to-one ratio to the combination (COMBO) or sunitinib (SUN) arm. Overall survival (OS) was assessed from enrollment while progression free survival (PFS) and tumor response was assessed per RECIST 1.1 (independent blinded central review) from start of sunitinib. Results: From April 2014 to January 2017, 88 patients (58 COMBO, 30 SUN) were randomized. In the COMBO arm, 2 patients did not receive ilixadencel, 10 did not receive sunitinib, and 1 did not have any follow up CT-scan. Five patients in the SUN arm never received sunitinib. Five patients (11%) in the COMBO arm had a complete response as best response versus one patient (4%) in the SUN arm. Confirmed ORR was 42.2 % (19/45) versus 24.0% (6/25). Median Duration of Response was 7.1 months versus 2.9 months. Median PFS was 11.8 months versus 11.0 months. Median OS has still not been reached in either group. As of July 2019, 57% and 43% were alive in the COMBO and SUN arms, respectively. Treatment with ilixadencel did not add any treatment-related Grade 3-4 Adverse Events. Conclusions: Compared to sunitinib monotherapy, combined treatment with ilixadencel followed by sunitinib demonstrated higher confirmed ORR, including several complete responses and longer duration of response, in patients with newly diagnosed synchronous mRCC. Clinical trial information: 02432846.

The Changing Landscape of Therapeutic Cancer Vaccines—Novel Platforms and Neoantigen Identification

“…In addition, a vaccine using yeast cell wall particles (YCWP) to load autologous tumor lysate into autologous DCs is being studied for melanoma and for solid tumors (35)(36)(37)(38); in a phase II trial, the YCWP vaccine resulted in prolonged disease-free survival in patients with resected melanoma, with a disease-free interval of >3 months, compared with those who received unloaded YCWP (36,37). A further phase II study of ilixadencel, an off-theshelf, cell-based immune primer, in combination with sunitinib, pre-and post-nephrectomy, showed greater rates of complete and objective response, but similar progression-free survival, compared with sunitinib monotherapy in patients with newly diagnosed metastatic renal cell carcinoma (39).…”

Cell‐Based Delivery Systems: Emerging Carriers for Immunotherapy

“…Remarkably, according to the global Phase II MERECA clinical trial (nct02432846), the total remission rate of patients with advanced metastatic mRCC treated with the combination of ilixadencel and sunitinib was twice as high as that of sunitinib alone. [ 90 ] Moreover, the treatment of solid tumors, such as kidney cancer, liver cancer, gastrointestinal stromal tumors, head and neck tumors, non‐small cell lung cancer and gastric cancer with DC vaccines, is also under accelerated preclinical and clinical development. [ 91 ]…”

New approaches to first-line treatment of advanced renal cell carcinoma

“… 65 – 67 In the randomized phase II MERECA study, the dendritic cell vaccine ilixadencel followed by sunitinib was compared with sunitinib as a first-line treatment, with improved ORR but similar PFS and OS results. 68 …”