Ilixadencel/Sunitinib Combo Showcases Promising Survival Benefit in mRCC

The off-the-shelf immune primer ilixadencel in combination with sunitinib (Sutent) showcased an encouraging, clinically meaningful survival benefit when used in the first-line treatment of newly diagnosed patients with metastatic renal cell carcinoma (mRCC), according to updated data from the phase 2 MERECA trial (NCT02432846).¹

Updated results demonstrated a median overall survival (OS) of 35.6 months with the ilixadencel combination versus 25.3 months with single-agent sunitinib. Previously, in August 2020, the median OS had not yet been reached in the combination arm compared with 25.0 months in the monotherapy arm.

“The observed difference of 10 months in median OS for the ilixadencel combination group versus the control group is substantial and clinically meaningful,” Peter Suenaert, MD, PhD, the Chief Medical Officer at Immunicum, stated in a press release.² “Although the randomized, controlled study was not statistically powered for the OS end point, the data announced today suggests that ilixadencel has the potential to become a promising treatment option for these patients by improving survival outcomes when combined with standard-of-care cancer therapies.”

As of February 2021, investigators reported a separation in the Kaplan-Meier survival curves that favored ilixadencel/sunitinib; this was in line with the projected separation from August 2020. Additionally, 41% (n = 23/56) of patients were alive in the combination arm versus 30% (n = 9/30) of those in the monotherapy arm. 

In the follow-up, all 5 patients who received ilixadencel/sunitinib and had complete tumor response as their best response were still alive, while 1 patient who achieved a complete response with sunitinib monotherapy died during the first follow-up period. 

Survival updates for patients in the MERECA study will be announced for each consecutive 12-month follow-up period, according to Immunicum AB (publ), the developer of ilixadencel.

“These updated results from the phase 2 MERECA trial underscore the positive impact on OS that ilixadencel may achieve for [patients with] kidney cancer,” Sven Rohmann, MD, PhD, CEO ar Immunicum, added in the release. “With today’s longer follow-up data, the encouraging signal observed has matured and builds our conviction to bring ilixadencel to patients in need.”

Ilixadencel is an immunotherapy developed for the treatment of solid tumors, with an active ingredient of activated allogeneic dendritic cells that are derived from healthy blood donors. Injection of these cells into the tumor generates an inflammatory response which leads to tumor-specific stimulation of cytotoxic T cells.

MERECA is an exploratory, international, randomized, controlled, open-label clinical trial in which enrolled 88 newly diagnosed patients with intermediate- to poor-prognosis mRCC.

To be eligible for enrollment, patients had to be aged 18 years or older and have newly diagnosed (defined as less than 6 months) mRCC, and at least 1 computed tomography–verified metastasis of at least 10 mm for which complete metastasectomy is not planned. Additionally, patients must have planned resection of their primary tumor and a primary tumor diameter of at least 40 mm.³

Patient with a life expectancy of less 4 months; central nervous system metastasis that is symptomatic, progressing, untreated, or that requires current therapy; and active autoimmune disease that requires treatment with systemic immunosuppressive agents, were excluded. Moreover, if a patient had a Karnofsky performance status of less than 70%, they were not permitted. 

The primary end points of the trial included OS and 18-month OS, while secondary end points comprised safety and tolerability, tumor response, and immunological profiling, including T-cell infiltration.

In the trial, participants were randomized in a 2:1 fashion to receive either 2 intratumoral doses of ilixadencel prior to nephrectomy and subsequent treatment with sunitinib, or sunitinib monotherapy post nephrectomy.

Preliminary results from the trial showed that among 70 patients evaluable for overall response per RECIST v1.1 criteria and central blinded review, complete tumor response was achieved by 11% of patients who received the ilixadencel combination (n = 5/45) versus 4% of those given single-agent sunitinib (n = 1/25).

The 18-month survival rates were comparable in the ilixadencel/sunitinib and sunitinib arms, at 63% and 66%, respectively. At that time point, the median progression free survival and time to progression also proved to be similar between the 2 treatment arms. 

Overall safety and tolerability data were also comparable between the 2 arms. The findings were determined to be in line with prior data reported from other clinical trials of ilixadencel.

References

1. Immunicum announces encouraging signs of survival benefit in phase II MERECA trial of ilixadencel in kidney cancer. News release. Immunicum AB (publ). February 22, 2021. Accessed February 23, 2021. https://bit.ly/3sdSBia
2. Immunicum AB (publ) announces positive phase II MERECA topline results including complete tumor responses in metastatic renal cell carcinoma patients. News release. Immunicum AB (publ). August 29, 2019. Accessed August 26, 2020. https://bit.ly/2zxwutL
3. Intratumoral vaccination with intuvax pre-nephrectomy followed by sunitinib post-nephrectomy vs sunitinib post-nephrectomy in newly diagnosed metastatic renal cell carcinoma (mRCC) (MERECA). ClinicalTrials.gov. Updated September 4, 2019. Accessed February 23, 2021. https://clinicaltrials.gov/ct2/show/NCT02432846