Ilixadencel Plus Sunitinib Shows Survival Benefit in Metastatic RCC

The combination of the off-the-shelf cancer immune primer Ilixadencel and sunitinib (Sutent) has demonstrated promising survival benefit when used as a frontline treatment for newly diagnosed patients with metastatic renal cell carcinoma (mRCC), according to updated data from the phase 2 MERECA trial (NCT02432846).¹

Results showed that as of August 2020, the median overall survival (OS) had not yet been reached in those who received the combination compared with 25.0 months in those who were given sunitinib alone. Moreover, the findings continue to illustrate a separation in Kaplan-Meier survival curves with the median OS in favor of the experimental cohort.

Forty-three percent (n = 24/56) of patients on the ilixadencel/sunitinib arm were still alive versus 33% (n = 10/30) of those on the control arm. Moreover, all 5 patients who achieved complete responses (CRs) with the combination were still alive at the time of the follow-up, while the 1 patient who achieved a CR with sunitinib alone died during the first follow-up period, as was previously reported.

“As our largest and longest study, the phase 2 MERECA trial continues to give us insight into the potential efficacy of ilixadencel in combination with standard-of-care in patients with metastatic tumors,” Alex Karlsson-Parra, associate professor, chief scientific officer, and CEO of Immunicum, stated in a press release. “As such, we are encouraged that the data at this stage show that only 2 injections of ilixadencel continue to have an impact on survival of patients as the median OS of that group has not yet been reached.”

Immunicum AB (publ), the developer of ilixadencel, announced that follow-up survival data will continue be collected and updated at 6-month intervals. The next data update from the trial is anticipated to be released in Q1 2021.

“As the data continue to mature, we are able to further analyze which patients most benefit from ilixadencel and design our future studies to maximize our understanding of therapeutic potential for patients,” Karlsson-Parra added.

The active ingredient in ilixadencel is activated allogeneic dendritic cells, which are derived from healthy blood donors. The intratumoral injection of these cells is designed to elicit an inflammatory response, which then prompts tumor-specific activation of cytotoxic T cells.

In the exploratory, international, controlled, open-label, phase 2 trial, a total of 88 newly diagnosed patients with intermediate- and poor-prognosis mRCC were enrolled. A total of 88 participants were then randomized 2:1 to receive treatment with either 2 intratumoral doses of ilixadencel before nephrectomy followed by sunitinib or sunitinib alone following nephrectomy; these patients were subsequently followed for survival.

Patients must have had newly diagnosed disease with 1 or more computed tomography–verified metastasis, planned resection of the primary tumor, and a primary tumor diameter of 40 mm or more, to be included in the trial. Moreover, patients had to be candidates for frontline sunitinib to be initiated 5 to 8 weeks following nephrectomy and have had acceptable hematological parameters to participate.

Patients who had a life expectancy of 4 months or less; central nervous system metastasis that was symptomatic, progressing, or required current therapy; active autoimmune disease; and a Karnofsky performance status of 70% or less were not permitted to enroll.

The primary end points of the trial were median OS and 18-month OS rates, while key secondary end points included safety and tolerability, tumor response, and immunological profiling.

Topline data from the trial showed that a total of 70 patients were evaluable for overall response per RECIST v1.1 criteria with a central blinded review; 45 patients were enrolled to the experimental arm, while 25 were enrolled to the control arm.²

Results showed that 11% (n = 5) of those on the combination arm achieved a CR versus 4% (n = 1) of those on the control arm. Additionally, the 18-month OS rate was 63% with ilixadencel/sunitinib versus 66% with sunitinib alone. The median progression-free survival and time to progression were reported to have been comparable between the 2 treatment arms. The data pertaining to immunological profiling, which included T-cell infiltration findings, were reported to require further examination.

Moreover, the company reported that the data regarding safety and tolerability between the 2 arms proved to be similar and they were consistent with clinical data that had previously been reported with the off-the-shelf cancer immune primer.

In May 2020, ilixadencel was granted a Regenerative Medicine Advanced Therapy designation from the FDA for the treatment of patients with mRCC. The regulatory decision was based on prior data from MERECA.³

References:

1. Immunicum AB (publ) announces update on survival data from phase II MERECA trial of ilixadencel in kidney cancer. News release. Immunicum AB (publ). August 18, 2020. Accessed August 26, 2020. https://bit.ly/3aXhBTg.
2. Immunicum AB (publ) announces positive phase II MERECA topline results including complete tumor responses in metastatic renal cell carcinoma patients. Immunicum AB (publ). August 29, 2019. Accessed August 26, 2020. https://bit.ly/2zxwutL.
3. Immunicum AB (publ) receives Regenerative Medicine Advanced Therapy designation from FDA for ilixadencel in kidney cancer. News release. Immunicum AB (publ). May 6, 2020. Accessed August 26, 2020. https://bit.ly/3aZWJuE.