Nyligen publicerades en interimsanalys av Merck KGaA och Pfizers kliniska studie JAVELIN i njurcancerpatienter i ansedda New England Journal of Medicine. Resultaten var positiva och ger bränsle åt de redan höga förväntningarna på kombinationsbehandlingar inom immunonkologi – svenska Immunicum är ett bolag som följer utvecklingen med stort intresse.

De interimdata som publicerats i New England Journal of Medicine (NEJM) av de bägge läkemedelsjättarna Pfizer och tyska Merck KGaA visar att behandling med en kombination av checkpoint-hämmaren Bavencio (avelumab) och tyrosine kinase-hämmaren Inlyta (axitinib) gav bättre effekt i njurcancerpatienter än dagens standardbehandling med sunitinib som monoterapi.

Effektmåttet progressionsfri överlevnad (PFS) förbättrades med i snitt 5 månader jämfört med hos patienter som fått standardbehandlingen, samtidigt som objective response rate (ORR), ett effektmått som vanligen definieras som andelen patienter vars tumörbörda minskat, också dubblades. Studien, kallad JAVELIN Renal 101 fortgår och kommer även att utvärdera det primära effektmåttet overall survival (OS).

För patienter med framskriden cancer är varje månad som sjukdomen kan fördröjas värdefull. Immunonkologi har under en längre tid hyllats som cancerforskningens viktigaste genombrott, och de senaste framstegen ligger helt i linje med den rådande hypen av olika kombinationsterapier inom immunonkologifältet.

Sverige har flera bolag inom det glödheta immunonkologifältet och för Immunicum, vars läkemedelskandidat Ilixadencel också just nu utvärderas som kombinationsterapi i en fas II-studie (MERECA) i patienter med metastaserad njurcancer, är resultaten från Pfizer/Merck KGaAs kliniska studie extra intressanta. BioStock kontaktade bolagets vd Carlos de Sousa för en kommentar.

» The results from the Phase III Merck KGaA/Pfizer trial in Renal Cell Carcinoma are positive for both patients with RCC as well as Immunicum, as the outcome of the study directly validates our use of the combination approach in cancer. « – Carlos de Sousa, vd Immunicum 

Carlos de Sousa, vd Immunicum

Carlos de Sousa, vd Immunicum

Merck KGaA and Pfizer recently presented positive results from their Phase III study comparing the combination of avelumab and axitinib in contrast to sunitinib as a monotherapy. How does this data relate to Immunicum and the Phase II MERECA trial in metastatic Renal Cell Carcinoma?

– The results from the Phase III Merck KGaA/Pfizer trial in Renal Cell Carcinoma are positive for both patients with RCC as well as Immunicum, as the outcome of the study directly validates our use of the combination approach in cancer.

Could you elaborate on how it specifically validates your approach with ilixadencel used in combination therapies?

– In the Merck KGaA/Pfizer trial, they explored the combination of a checkpoint inhibitor (CPI) and a tyrosine kinase inhibitor (TKI), in contrast to the standard-of-care TKI, sunitinib alone. The outcome of their trial indicates that the combination of a CPI and a TKI have a natural expected efficacy benefit over the TKI alone. They also both act on the same side of the cancer immunity cycle by blocking the defense mechanisms of the tumor cells and killing them.

– In comparison, whether used alone or in combination with the TKI sunitinib as is done in the MERECA study, ilixadencel’s mechanism of action is as an immune system activator designed to be combined with, and hopefully improve the efficacy of, all forms of cancer treatment including CPIs and TKIs. Ilixadencel therefore remains a complementary approach and a possible option to support the stimulation of the immune system to better target and attack cancer cells.

» The endpoints [from MERECA] will be evaluated when we announce the topline results in mid-2019. Based on the outcome of these results, the next step would be to run a regulatory-focused pivotal trial in combination with the newest classes of drugs, such as CPIs. «

The Phase II MERECA trial is designed as an exploratory study. What is the difference compared to a pivotal trial and what can we then expect to learn from the upcoming top line trial results in mid-2019?

– The clinical drug development process is lengthy and follows specific steps and guidelines to ensure the product has been properly tested and effectively evaluated. In most cases, Phase III clinical trials are pivotal and result in statistically significant results that can be used to provide evidence for a drug marketing approval. Only in rare circumstances are Phase IIa trials designed to be pivotal from a regulatory standpoint.

– In this case, as MERECA is a Phase IIa, exploratory clinical trial, it was not intended to be a pivotal regulatory trial. The study design is focused on providing valuable information on patient survival, safety, tumor-specific immune activation and potential clinical efficacy. These endpoints will be evaluated when we announce the topline results in mid-2019. Based on the outcome of these results, the next step would be to run a regulatory-focused pivotal trial in combination with the newest classes of drugs, such as CPIs.

Combination treatments seem to be dominating current discourse with regards to the field of immuno-oncology. How does ilixadencel fit in among the other numerous novel combination therapies in development?

– There will always be a need for various treatment approaches as all cancers and patients are different. Ilixadencel’s position in this space is as an immune primer that has the potential to be broadly applied in combination with CPIs, TKIs and/or other standard-of-care treatments with the ultimate goal for it to become a backbone therapy for the treatment of solid tumors.

» As novel therapies in the immuno-oncology field enter the market, we will continue to monitor the development in the space and stay up-to-date on the best possible combinations for ilixadencel. As mentioned earlier, we have the possibility of combining with any of these classes of drugs, and with a benefit in terms of safety. «

The Bavencio & Inlyta-combo is expected by analysts to face fierce competition from another combination, that of Inlyta and Merck’s mega-blockbuster Keytruda. How do you keep an edge in this competetive landscape?

– As novel therapies in the immuno-oncology field enter the market, we will continue to monitor the development in the space and stay up-to-date on the best possible combinations for ilixadencel. As mentioned earlier, we have the possibility of combining with any of these classes of drugs, and with a benefit in terms of safety. This can already be seen in our ILIAD study, in which we will evaluate ilixadencel as an immune primer combined with checkpoint inhibitors in three indications: head and neck cancer, non-small cell lung cancer and gastric cancer. The first patient of the Phase Ib/II study was recently dosed, and we expect to have the first announcement related to the trial in the second half of 2019.

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