The addition of the off-the-shelf cancer immune primer ilixadencel to sunitinib (Sutent) trended toward a benefit in overall survival (OS) compared with sunitinib alone as a first-line treatment for patients with newly diagnosed metastatic renal cell carcinoma (RCC), according to updated results of the phase II MERECA trial (NCT02432846) presented during the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium.1,2
Updated data from December 2019 confirm the separation in survival curves in favor of the ilixadencel arm, which was projected by Kaplan-Meier curves in the prior readout of data; results showed that 54% of patients who received ilixadencel/sunitinib were alive compared with 37% of those who received sunitinib alone. The median OS value in either arm cannot yet be calculated, as the data remain immature, Immunicum AB (publ), the developer of ilixadencel, stated in a press release.
Moreover, the extended analysis showed that, of 70 evaluable patients, the combination regimen demonstrated a confirmed objective response rate (ORR) of 42.2% compared with 24.0% for sunitinib alone.
“The updated data emphasize that both tumor responses and the durability of patient response with ilixadencel treatment as part of a combination regimen were better compared to sunitinib alone,” principal investigator Magnus Lindskog, MD, PhD, associate professor, clinical oncologist at Uppsala University Hospital, Sweden, stated in the press release. “The addition of ilixadencel did not increase either the frequency or the severity of side effects. However, longer follow-up is required before we with certainty can comment on any differences in long-term survival.”
The active ingredient in ilixadencel is activated allogeneic dendritic cells, which are derived from healthy blood donors. The intratumoral injection of such cells is designed to produce an inflammatory response, which then elicits tumor-specific activation of cytotoxic T cells.
The exploratory, international, randomized, controlled, open-label, phase II MERECA trial enrolled 88 newly diagnosed, intermediate and poor-prognosis patients with mRCC. Patients were randomized 2:1 to receive either 2 intratumoral doses of ilixadencel prior to nephrectomy and subsequent treatment with sunitinib or sunitinib alone following nephrectomy.
To be eligible for enrollment, patients must have had newly diagnosed RCC with ≥1 CT-verified metastasis, had planned resection of the primary tumor, a primary tumor diameter of ≥40 mm, was a candidate for frontline sunitinib to be initiated 5 to 8 weeks after nephrectomy, and had adequate hematological parameters. Some exclusion criteria included those with a life expectancy of <4 months; central nervous system metastasis that was symptomatic, progressing, or required current therapy; active autoimmune disease; and a Karnofsky performance status <70%.
The primary endpoints were median OS and 18-month OS rates; secondary endpoints included evaluation of safety and tolerability, tumor response, and immunological profiling.
Overall, the median age was 63 years old, and 74% of patients were male. Additionally, 72% of patients had International Metastatic Renal-Cell Carcinoma Database Consortium (IDMC) intermediate-risk disease and 28% patients had IDMC poor-risk disease. A total 22.5% of patients had sarcomatoid features.
The median progression-free survival was 11.8 months for ilixadencel/sunitinib and 11.1 months for sunitinib alone. When stratified by risk group, the median OS was immature was immature in the intermediate-risk group; in the poor-risk group, the median OS was 10.6 months for the combination and 9.3 months for sunitinib alone.
According to independent blinded review, the median duration of response was 7.1 months for ilixadencel/sunitinib compared with 2.9 months for the control arm. The investigators also noted that patients with sarcomatoid features were not associated with responses to the combination.
Regarding safety, the most common treatment-related adverse event with ilixadencel plus sunitinib was pyrexia; moreover, 57% of patients on the combination arm developed de novo ilixadencel-specific alloantibodies.
At the preliminary analysis, earlier results showed that 5 patients (11%) on the ilixadencel arm experienced a complete response compared with 1 patient (4%) in the control arm.3 Moreover, the 18-month OS rates were 63% with ilixadencel compared with 66% in the control group.
“The fact that ilixadencel, when combined with subsequent sunitinib treatment, induces a nearly 2-fold increase in the confirmed objective response rate and more complete responses when compared to sunitinib monotherapy, is of course highly encouraging. Additionally, the favorable early separation of the Kaplan-Meier curves that now has been confirmed and the long-term survival projections are clearly interesting,” Alex Karlsson-Parra, CSO, associate professor and interim CEO of Immunicum, stated in the press release. “We continue our discussions with regulatory bodies to define the next step in the development of ilixadencel as a treatment for a range of solid tumors.”
1. Immunicum AB (publ) presents updated data from phase II MERECA trial of ilixadencel in kidney cancer at ASCO-SITC Clinical Immuno-Oncology Symposium [news release]. Immunicum AB (publ). Published February 6, 2020. https://bit.ly/38p9L2L. Accessed February 12, 2020.
2. Lindskog M, Laurell A, Kjellman A, et al. A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma. J Clin Oncol. 2020;38(suppl; abstr 11).
3. Immunicum AB (publ) announces positive phase II MERECA topline results including complete tumor responses in metastatic renal cell carcinoma patients. Immunicum AB (publ). Published August 29, 2019. https://bit.ly/2zxwutL. Accessed August 29, 2019.
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