Ilixadencel Plus Sunitinib Induces Complete Responses in Metastatic RCC

The combination of the off-the-shelf cancer immune primer ilixadencel and sunitinib (Sutent) elicited a 11% complete response (CR) rate in patients with metastatic renal cell carcinoma (RCC), according to topline findings from the phase II MERECA trial (NCT02432846).

The median overall survival (OS) has not been reached in either the combination arm or in patients who received sunitinib alone following nephrectomy. Full findings will be published in a peer-reviewed journal and/or presented at an upcoming medical meeting, Immunicum AB (publ), the developer of ilixadencel, reported in a press release.

“As a clinical oncologist specialized in treating kidney cancer patients, the prospect of an immune primer that can support the achievement of complete responses in advanced-stage patients with a positive tolerability and safety profile is extremely exciting, especially in an indication in which complete responses are rare,” study investigator Magnus Lindskog, MD, associate professor of Uppsala University Hospital, stated in the press release. “If this response rate can be confirmed in a larger pivotal trial, it would represent a major step forward for the treatment of kidney cancer patients.”

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 is symptomatic, progressing, or requires 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.

Seventy patients were evaluable for overall response using RECIST v1.1 criteria with a central blinded review; 45 patients were in the ilixadencel group, and 25 were patients in the control arm.

Results showed that 5 patients (11%) on the ilixadencel arm experienced a CR compared with 1 patient (4%) in the control arm. Moreover, the 18-month OS rates were 63% with ilixadencel compared with 66% in the control group. Additional follow-up will continue for these patients to gain further survival data.

Moreover, the median progression-free survival and time to progression were similar in the 2 arms. However, the immunological profiling, which includes T-cell infiltration data, requires further analysis, the company stated in the press release.

The safety and tolerability data were similar between the 2 arms, and was consistent with prior clinical findings with ilixadencel.

“Our main objective for MERECA was to explore the therapeutic benefit of ilixadencel in combination with a standard treatment regimen. The surprising number of complete responses in advanced-stage cancer patients is particularly encouraging and highly supportive of our vision for ilixadencel as a backbone therapy in modern cancer treatment regimens,” Carlos de Sousa, CEO of Immunicum, stated in the press release. “We are eager to conduct the full analysis of the data and use that to refine and accelerate ilixadencel’s clinical development.”

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. Accessed August 29, 2019. https://bit.ly/2zxwutL.