Ilixadencel is a cell-based, allogeneic, off-the-shelf product aimed at priming the anticancer immune response when injected intratumorally. The phase II MERECA study evaluated this allogeneic dendritic cell product given with sunitinib in 88 patients with metastatic renal cell carcinoma. The study did not meet its co-primary endpoints; nevertheless, the results were considered encouraging by experts at the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium.1
Magnus Lindskog, MD, PhD
“Compared to sunitinib monotherapy, combined treatment with ilixadencel followed by sunitinib demonstrated higher confirmed objective response rates, including several complete responses and longer duration of response,” said Magnus Lindskog, MD, PhD, of Uppsala University in Sweden.
MERECA Study Details
In the multicenter, randomized, phase II MERECA trial, the intratumoral administration of ilixadencel (two doses, 2 weeks apart) before nephrectomy, followed by sunitinib postnephrectomy, was compared with sunitinib monotherapy postnephrectomy as first-line systemic therapy in 88 patients with newly diagnosed synchronous metastatic renal cell carcinoma. The co-primary endpoints were 18-month overall survival and overall survival in total.
At a median time of 18 months, 70 patients were evaluable by blinded independent review. At this time, the median progression-free survival was 11.8 months vs 11.0 months, respectively, and overall survival was 63% and 66%, respectively. Median overall survival was not reached in either group.
Interestingly, however, despite missing these endpoints, a possible survival benefit down the line seems to be emerging. “There is a late separation of the curves, as we see in many immunotherapy trials,” Dr. Lindskog said. The Kaplan-Meier curves are fairly on top of each other to start with and then start to separate after about 2 years.”
“Also, in the ilixadencel combination group, we actually had five complete responders (11%), all of whom are alive with a minimum follow-up of 30 to 33 months. In the control group receiving sunitinib alone, there was one complete responder (4%), who remained in response but died after 41 months,” he added.
The confirmed respective objective response rates were 42.2% and 24.0%, and the median durations of response were 7.1 and 2.9 months. At the time of the presentation, the combination arm had 54% of patients still alive, compared to 34% of the sunitinib arm.
“We do have more durable or confirmed responses in the combination arm, and we also have some complete responses that could be confirmed,” he said. By risk group, he added, “it seems that the possible activity of this combination treatment is driven by patients at intermediate risk, whereas those with high-risk disease have a poor prognosis, irrespective of treatment arms in this study.”
Treatment with ilixadencel did not increase treatment-related grade 3 to 4 adverse events over sunitinib alone.
For this treatment, healthy donors undergo leukapheresis; monocytes are isolated and differentiated into mature dendritic cells, and patients receive a “cocktail of several agents” aimed at inducing Th1-like pro-inflammatory activity in these cells. Ultimately, a single donor produces about 100 vials, with 2 vials per patient injected into either the primary or metastatic tumor.
“We believe that ilixadencel produces a lot of chemokines and cytokines that both recruit and activate natural killer cells, and possibly bystander dendritic cells from the patient. These cells invade the tumor and ultimately travel to the lymph nodes for cross-presentation to CD8-positive T cells of tumor antigens. No antigen is given; instead, this approach relies on the full repertoire of new antigens already present in the tumor,” he explained.
DISCLOSURE: The study was funded by Immunicum AB, Stockholm, Sweden. Dr. Lindskog has served as a consultant or advisor for Pfizer and Bristol-Myers Squibb and has received honoraria from Pfizer, Bristol-Myers Squibb, and Ipsen.
1. Lindskog M, Laurell A, Kjellman A, et al: A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib vs sunitinib alone in synchronous metastatic renal cell carcinoma. 2020 ASCO-SITC Clinical Immuno-Oncology Symposium. Abstract 11. Presented February 6, 2020.
Ilixadencel is essentially a dendritic cell vaccine without preloaded antigens. In the MERECA study, ilixadencel produced “a great signal,” though this approach is still very experimental, said the study’s invited discussant, Navid Hafez, MD, MPH, of Yale Cancer Center. Dr. Hafez is a member of the ...