MERECA Q&A – English
What are the main findings and conclusions from the MERECA study?
The topline data on survival benefit in all patients showed that a higher percentage of ilixadencel patients were alive as per data cut-off in July 2019. Among the responders, meaning the patients with Complete Responses (CR) and Partial Responses (PR), the addition of ilixadencel to sunitinib induced stronger and more durable tumor responses. In detail, the results from the study show that complete tumor response was reached in 5 out of 45 evaluable patients treated with the combination of ilixadencel and sunitinib. This result in itself was unexpected to both us and the primary investigators since complete tumor response is achieved when all signs of cancer disappear in response to the treatment. Tumor eradication is the ultimate goal of all cancer treatments and is rarely achieved in the metastatic cancer setting, including kidney cancer.
Taken together, the results indicate that ilixadencel provided a systemic therapeutic benefit while maintaining a positive safety and tolerability profile. These data support the continued clinical development of ilixadencel as an immune primer in RCC and other solid tumors, to provide cancer patients with additional treatment alternatives.
What additional understanding did the further analysis give?
The most important findings of the detailed analysis are:
- Survival as of July 2019 was 57% (32 out of 56) in patients who were treated with ilixadencel in combination with sunitinib, compared with 43% (13 out of 30) in patients treated with sunitinib alone.
- In terms of tumor responses: the study showed a longer median Duration of Response (7.1 months versus 2.9 months in the sunitinib monotherapy group) within the 18-months follow-up; a higher percentage of responses ongoing at the 18-months follow-up, 60% (12 out of 20 patients) in the combination group versus 33% (4 out of 12 patients) in the sunitinib monotherapy group; and a higher percentage of Responders alive at last patient contact, 85% (17 out of 20 patients) in the combination group versus 58% (7 out of 12 patients) in the sunitinib monotherapy group.
- Tumor infiltration showed a high variability of CD8+ T cells infiltration (as measured by the area of CD8-staining versus the total tumor area) within the treatment groups, between different samples taken from the same tumor and also within Complete Responders. That indicates that the intratumor infiltration of CD8+ T cells by itself, without considering CD8+ T cell specificity and functionality, does not explain the systemic therapeutic impact of ilixadencel when combined with sunitinib.
- The further analysis confirmed the overall safety and tolerability data communicated in August. The data was similar in both treatment groups, meaning that the addition of ilixadencel to sunitinib did not add toxicity.
The results from the further analysis is discussed in more detail in a presentation given by Immunicum’s CEO, Carlos de Sousa, found on the Company website, immunicum.com. This presentation aims at answering many of detailed questions which may arise.
Why isn’t it possible to calculate the median Overall Survival rate even though less than half of the patients in the treatment arm are alive?
The median Overall Survival final value cannot yet be calculated in either group as the data from a scientific and statistical perspective is not mature enough. There are several patients still alive and individual survival data can have an impact on the final value for the median Overall Survival.
Follow-up on survival data will be collected and updated continuously at 6-month intervals, with the first update expected in January 2020. Based on this ongoing follow-up, Immunicum will communicate the median OS values once the data becomes more mature.
Why did the control arm have a “better” 18 months survival rate than the ilixadencel arm?
The results are very similar and reflect that both treatment groups responded well to the treatment. However, survival at 18 months is too early to draw any conclusions about any differences in the subsequent median Overall Survival, particularly with immunotherapies. We need to continue to follow these patients for survival which we will do at 6-month intervals.
Why is the 18 months survival rate (66%) clearly higher in the control group compared to data from the CARMENA study (Mejean et al, 2018) where newly diagnosed mRCC patients with metastasis at diagnosis (synchronous mRCC) given sunitinib post-nephrectomy had an 18 months survival rate of approximately 45%?
The most likely explanation is that the proportion of high-risk patients was lower in our study (30% vs 44%).
Is there any explanation as to why it is not possible to draw any conclusion on tumor infiltration?
The high variability of CD8-stained area in the tumors within the treatment groups, between different samples taken from the same tumor and also within Complete Responders, indicate that the intratumor infiltration of CD8+ T cells by itself, without considering CD8+ T cell specificity and functionality, does not explain the systemic therapeutic impact of ilixadencel when combined with sunitinib considering the good systemic therapeutic effect on tumor responses.
Also, remember the MERECA-study is an exploratory study where infiltration was an exploratory secondary endpoint. Infiltration is not a regulatory endpoint and is not needed to design and conduct future clinical studies. In that context, achieving 5 complete responses out of 45 patients, shrinking or clearing tumors at a higher rate and for a longer time is what is important rather than being able to fully validate the mode-of-action. We will nevertheless continue to explore ways of identifying the sub-type of CD8+ T cells having the highest anti-tumor activity.
What are Immunicum’s next steps?
We will now complete the analysis of the full data package from the MERECA study, share the data with regulatory authorities as well as potential future partners and we will also start the preparations for the initiation of a pivotal study in RCC, which can be done by us alone or in collaboration with a potential licensing partner.