Ilixadencel Improves Responses, Extends Survival in Newly-diagnosed Metastatic Kidney Cancer, Trial Results Show

Ilixadencel Improves Responses, Extends Survival in Newly-diagnosed Metastatic Kidney Cancer, Trial Results Show

Adding Immunicum‘s ilixadencel to standard surgical and medical treatment for newly-diagnosed metastatic renal cell carcinoma — the most common form of kidney cancer — increases patient responses, duration of response, and appears to help people live longer, updated findings from a Phase 2 trial show.

However, more time and study is needed to confirm the survival data, researchers say.

Those results were presented at the the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium, in Orlando, Florida, Feb. 6–8, in a presentation titled, “A randomised phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma.”

Ilixadencel is an immune primer designed to increase the body’s defenses against cancer cells. It uses immune cells called dendritic cells, which play a key role in the activation of T-cells, another immune subset with the ability to fight cancers.

The dendritic cells are collected from healthy donors. After isolation, they undergo a procedure to become highly activated and produce molecules that induce a strong immune response. The dendritic cells are injected directly into patients’ tumors, causing an inflammatory response that promotes the recruitment and activation of T-cells that then attack cancer cells.

Unlike other dendritic cell-based therapies, the approach does not work as a vaccine, in which the immune system becomes primed toward specific cancer targets. Rather, it is based on a more broad activation of the immune system.

The open-label, randomized MERECA Phase 2 trial (NCT02432846) was designed to assess the effects of adding ilixadencel to standard treatment for newly-diagnosed metastatic renal cell carcinoma — surgery followed by treatment with the oral, small molecule inhibitor Sutent (sunitinib).

It included 88 participants with intermediate and high-risk disease who were divided in two groups. One received two ilixadencel injections, two weeks apart, followed by surgery to remove the affected kidney, and Sutent given five to eight weeks after surgery and until 18 months or disease progression. Patients in the second group were scheduled directly for surgery followed by Sutent.

The trial’s primary goal was to determine if the immune primer extended patients’ median overall survival, as well as the proportion of patients alive at 18 months. Secondary measures included safety, tolerability, objective response rate, time to disease worsening or death, and the degree of T-cell infiltration into tumors.

An prior analysis showed a high survival in both groups, with 63% of those in the ilixadencel group and 66% of patients in the control arm being alive at 18 months. The median time patients lived without their disease worsening and time to progression were similar in patients from both groups, as were overall safety and tolerability.

At the time, while survival was similar among both groups, survival curves were predicting better survival outcomes in the ilixadencel group at later timepoints. This was confirmed in the most recent analysis, corresponding to data collected in December 2019, which showed that more patients on ilixadencel were alive (54%) than those in the control group (37%).

In a post-study analysis, researchers also found that more patients on ilixadencel had a response to treatment (42.2% versus 24% for the control group), and that responses were stronger — with 11% versus 4% of patients attaining a complete tumor clearance — and longer in this patient group (7.1 months vs. 2.9 months).

Of note, the complete response rate achieved in the ilixadencel group is “exciting as compared to other combination studies in mRCC,” researchers wrote in the presentation. The closest was a 9% complete response achieved with a double immunotherapy combination of Opdivo (nivolumab) and Yervoy (ipilimumab).

“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,” associate professor Magnus Lindskog, clinical oncologist at Uppsala University Hospital, Sweden and principal investigator of the MERECA study, said in a press release.

“The addition of ilixadencel did not increase either the frequency or the severity of side effects,” he said. “However, longer follow-up is required before we with certainty can comment on any differences in long-term survival.”

Measures of tumor infiltration in surgically removed kidneys showed that people in both groups had similar levels of T-cells in their tumors, and that there was a high variability even in patients attaining complete responses; some had high levels of immune cell infiltration whereas other had not.

Because tumor infiltration was not enough to explain ilixadencel’s benefits, researchers now plan to examine specific subgroups of T-cells, “including specificity and functionality, to identify potential biomarkers for response.”

“The fact that ilixadencel, when combined with subsequent suntinib treatment, induces a nearly twofold increase in the confirmed Objective Response Rate and more complete responses when compared to sunitinib monotherapy, is of course highly encouraging,” said associate professor Alex Karlsson-Parra, chief science officer and interim CEO of Immunicum.

Ilixadencel is now moving toward late-stage clinical development.

“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,” Karlsson-Parra said.