The Stockholm-based immuno-oncology company (IO) Immunicum has several ongoing projects studying the effects of their off the shelf-cell-based candidate ilixadencelThe immunotherapy drug is being developed for the treatment of solid tumors. Its active ingredient consists of allogeneic dendritic cells from healthy blood donors, which are cells responsible for driving the body's immune response.
MERECA – Immunicum's largest study
Earlier this year, ilixadencel received so-called Regenerative Medicine Advanced Therapy (RMAT) status from the US Food and Drug Administration FDA. The agency's decision was based on previously communicated results from the company's main project, the MERECA Phase II clinical trial. The status gives Immunicum the opportunity to engage more closely with FDA officials in order to accelerate the development and review of the therapy. In fact, the company is currently preparing and discussing next steps and milestones for ilixadencel with the regulatory authorities.
MERECA is a global, exploratory, randomized phase II study designed to evaluate how ilixadencel works when combined with the commonly used tyrosine kinase inhibitor (TKI) sunitinib in metastatic renal cell carcinoma (RCC). The study includes a total of 88 patients newly diagnosed with metastatic renal cell carcinoma and whose prognosis is intermediate or poor. After being randomly divided into two groups, patients either received two intratumoral doses of ilixadencel before surgical removal of the tumor-affected kidney followed by treatment with sunitinib, while the other group was treated with sunitinib alone after surgery.
Study update indicates survival benefit
After the company announced a first set of top-line results from the MERECA study in 2019, Immunicum returned with the second round of data in February. These confirmed and reinforced the positive trends announced already last year. Most striking was the objective response rate (ORR), which measures the reduction in a patient's tumor size on repeat X-ray examinations. The ORR was 42 percent in the group treated with the combination therapy that included ilixadencel, compared to 24 percent in the group treated with sunitinib alone.
Just yesterday, the company released another round of new data from MERECA. The results show that median overall survival (OS) – a measure that indicates the average survival time for each patient group – has been achieved in the monotherapy group, while the final median survival in the ilixadencel group has not yet been reached. This is a strong indication that ilixadencel increases the chances of survival for the current patients when the candidate is combined with sunitinib.
Looking at patients with complete tumor response (CR) – meaning all tumor tissue has disappeared – the update shows that all five patients with CR in the ilixadencel group were still alive at the time of follow-up, while the only CR patient in the control group had already died at an earlier follow-up, another encouraging sign of ilixadencel’s treatment efficacy.
»Ilixadencel has shown deeper and more durable responses even in suboptimal conditions in which the standard-of-care is given months later. We can now move into the next phase of development in which ilixadencel, with the learnings from studies so far, will be tested in its most effective combinations and given to the patients who should benefit most. As every study will further reduce the development risk and expand the market potential of ilixadencel, we are certain that we can intrigue the likes of pharmaceutical companies that the asset adds value to their oncology portfolio« — Sijme Zeilemaker, COO for Immunicum.
COO comments on the new results
In the wake of the study update, it is becoming increasingly clear that ilixadencel has a positive effect in kidney cancer patients. Not only that, but when looking at the confirmed ORR data from the February update, these reflect similar results with other potent immunotherapy combinations, such as nivolumab plus ipilimumab. This is in line with the hypothesis that combination immunotherapies can play a major role in treating the most aggressive cancers.
BioStock contacted Immunicum's COO Sijme Zeilemaker to learn more about what the new results mean and what the company expects in the coming months.
Sijme Zeilemaker, first of all, what was your reaction when you first saw the results from this MERECA trial update?
– This was an exciting time point for us, as we knew the control group should be close to reaching the median OS based on the projections from the Kaplan-Meier survival graph from previous follow-ups. Every follow-up can potentially change the course of the survival graph as data further matures, so seeing the confirmation that the survival in both groups continued to have the observed difference was important and even a relief in some way. When we also saw that the patients who had a complete response were still alive was inspiring, as it continues to make a difference for those patients.
Could you tell us a bit more about what these results mean, specifically why they indicate a benefit from ilixadencel?
- The median OS is an important endpoint in later stage oncology studies to show that your candidate has a positive effect on survival for the average patient. However, we also know that for immunotherapies, this benefit is mostly visible for patients who are initially responding to the therapy, ie by reduced tumor size, called a tumor response. Therefore, already being able to pick up a difference in the average survival of patients is very positive, while we know that the benefit is most pronounced in patients who have a more durable response, as is the case in the patients who had a complete response.
How crucial has the RMAT designation from the FDA been so far, and how crucial will it be now that you have obtained these results?
- We are currently using the initial feedback from both FDA and EMA and the updated data from the MERECA study to design our next steps in development. If not for the RMAT, we would be limited in our interactions along these preparations. Now, we are in a position to plan our next meeting with the FDA to show our updated results and discuss updated designs. All in all, it will optimize our path to the market and make sure that the next study will be streamlined to their expectations.
In February, you announced a substantial difference in the Objective Response Rate between the two treatment groups (42 per cent in the combination group, compared to 24 per cent in the sunitinib monotherapy group). Has that changed since then?
- Unfortunately, our study could only follow patients for their tumor scans up to 18 months into the study, and subsequently only for survival status. We know from other studies that immunotherapies can even have a delayed deepening of the response, or later reduction of tumor size, but we cannot follow that beyond the initial follow-up. Therefore, these numbers will not change, but they do help us in designing our next study to make sure we can maximize our chances of picking up the efficacy benefit of ilixadencel.
Those numbers are similar to those seen with other prominent combination therapies currently in clinical trials. Could you comment on how ilixadencel is different from such therapies?
- First of all, it is important to see that the control arm with sunitinib is performing very similar in response and survival to other studies in kidney cancer with sunitinib. This underlines the benefit of ilixadencel on top of the standard-of-care and the quality of the clinical data obtained. Combination therapies have been able to increase the response and survival in kidney cancer and ilixadencel, despite given months before sunitinib, is indeed showing a similar pattern of improvement. Crucial to future combination regimens, ilixadencel has a favorable safety profile, which is something most of the current combination therapies are being limited by.
When should we expect another update from this trial?
- The survival follow-ups are at 6-month intervals, so we are looking towards Q1 2021 to receive and analyze the next results. Although we already know that there will be a difference in the median OS, it will be important for designing our next studies to interpret the size of the effect, so we are eager to await the median OS in the ilixadencel group to become final. However, we do hope it will take some time!
Given what you know so far, what are your overall expectations for ilixadencel in the long term and what business opportunities do you envision for Immunicum's primary asset?
- We have learned so much from the exploratory Phase II MERECA study and the smaller Phase I/II studies before that. Ilixadencel has shown deeper and more durable responses even in suboptimal conditions in which the standard-of-care is given months later. We can now move into the next phase of development in which ilixadencel, with the learnings from studies so far, will be tested in its most effective combinations and given to the patients who should benefit most. As every study will further reduce the development risk and expand the market potential of ilixadencel, we are certain that we can intrigue the likes of pharmaceutical companies that the asset adds value to their oncology portfolio.
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