The combination of ilixadencel plus sunitinib (Sutent) has evidenced favorable survival compared with sunitinib alone in patient with newly diagnosed metastatic synchronous renal cell carcinoma (mRCC), clinical sponsor Immunicum AB recently announced and will present at the 2020 American Society of Clinical Oncology-Society for Immunotherapy of Cancer Clinical Immuno-Oncology Symposium revealed a survival curve separation in the Phase II MERECA trial revealing promising signals.
Renal Cell Carcinoma
A relatively rare form of kidney cancer that includes fewer than 200,000 cases per year, it is the most common form of kidney cancer. The incidence of the disease varies according to geographic, demographic and, to a lesser extent, hereditary factors. There are some known risk factors, however the significance of other potential risk factors remains more controversial. The incidence of the cancer has been increasing in frequency worldwide at a rate of approximately 2–3% per decadeuntil the last few years where the number of new cases has stabilized.
The incidence of RCC varies between sexes, ages, races and geographic location around the world. Men have a higher incidence than women (approximately 1.6:1) and the vast majority are diagnosed after 65 years of age. Asians reportedly have a significantly lower incidence of RCC than whites and while African countries have the lowest reported incidences, African Americans have the highest incidence of the population in the United States. Developed countries have a higher incidence than developing countries, with the highest rates found in North America, Europe and Australia / New Zealand.
Metastatic Synchronous Renal Cell Carcinoma
Renal cell carcinoma is the most commonly diagnosed neoplasm of the kidney, its simultaneous diagnosis with gastrointestinal malignancy is a rarer but well reported phenomenon.
According to their website, Ilixadencel, Immunicum AB’s lead development candidate, is an off-the-shelf cell-based cancer immunotherapy indicated for treatment of hepatocellular carcinoma, gastrointestinal stromal tumors and mRCC.
The experimental drug uses dendritic cells sourced from healthy human donors that are specifically activated to produce significant amounts of vigorous immune stimulatory factors. By administration through intratumoral injection, these cells induce a local inflammatory reaction, leading to destruction of tumor cells, and recruitment and activation of the patient’s own dendritic cells into the tumor environment. The recruited dendritic cells will encounter and engulf dying tumor cells, including the full array of tumor specific proteins, called neoantigens, that will act as an antigen source to activate and educate the tumor specific T cells, specifically cytotoxic CD8+ T cells, resulting in a highly personalized and potent anti-tumor response.
Marketed at Sutent by Pfizer, it is an oral small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.
The study sponsor sought with the Phase II study to compare tumor response, progression free survival (PTS) and overall survival (OS) in newly diagnosed mRCC patients treated with Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy vs. Sunitinib post-nephrectomy in non-vaccinated patients. Put another way, the combination of ilixadencel plus Sutent has demonstrated favorable survival compared with sunitinib alone in patients with newly diagnosed metastatic synchronous renal cell carcinoma (mRCC).
The study was conducted at 28 sites located in the United States and Europe.
Discussion with Principal Investigator
As reported by Nichole Tucker with Targeted Oncology, “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 with sunitinib alone. The addition of ilixadencel did not increase either the frequency or the severity of adverse effects. However, longer follow-up is required before we, with certainty, can comment on any differences in long-term survival” reported principal investigator Magnus Lindskog, MD, PhD associate professor and clinical oncologist, Uppsala University Hospital, Sweden and principal investigator for the MERECA study.
By December 2019, the ilixadencel group rate of survival totaled 54% as compared to the 37% rate of survival associated with the sunitinib monotherapy group out of a total of 88 patients. Moreover, the research team found out of the ilixadencel group a 42% objective response rate as compared to only 24% for the sunitinib group. The responses went on for a median of 7.1 months with ilixadencel plus sunitinib 2.9 months for sunitinib alone. Median progression-free survival was higher in the ilixadencel group (11.8) vs. the combined group (11.0). The study sponsors don’t have sufficient data yet for the medial OS. However, by July 2019 of those patients that were on ilixadencel plus sunitinib, 57% were still alive while only 43% were alive of those on sunitinib monotherapy. The combining of ilixadencel with seniti didn’t lead to any serious adverse events.
The Sponsor: Immunicum AB
Immunicum AB, based in Sweden, is establishing a unique immuno-oncology approach through the development of allogeneic, off-the-shelf cell-based therapies. Their goal is to improve survival outcomes and quality of life by priming the patient’s own immune system to fight cancer. The company’s lead product ilixadencel, consisting of pro-inflammatory allogeneic dendritic cells, has the potential to become a backbone component of modern cancer combination treatments in a variety of solid tumor indications. Founded and based in Sweden, Immunicum is publicly traded on the Nasdaq Stockholm.
Business & Financials
Founded in 2002, they have raised over $50 million. They employ between 15 and 25. For the latest financial report, see the link.
Lead Research Sites
According to ClincialTrials.gov, Börje Ljungberg with Umeå University Hospital served as one of the study’s PI. This site represents a major hospital in northern Sweden. The hospital employs 5,600 people. It also serves as a teaching hospital for Umea University, with Faculty of Medicine as the responsible authority; 13 departments and two science centers, 12 undergraduate programs and several master programs. According to the recent Targeted Oncology report, Magnus Lindskog with Uppsala University also led the trial. Ranked as one of the top 100 universities in the world, Uppsala University is Sweden’s oldest university founded in 1477.
Börje Ljungberg, MD, Professor Umeå University Hospital
Magnus Lindskog, MD, PhD associate professor and clinical oncologist