Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma : A Randomized Phase 2 Study
Lindskog, M. (Department of Immunology. Genetics and Pathology. Uppsala University Hospital. Uppsala University)
Laurell, Anna (Department of Oncology. Akademiska University Hospital)
Kjellman, Anders (Department of Urology. CLINTEC. Karolinska University Hospital. Karolinska Institutet)
Melichar, Bohuslav (Department of Urology and Urological Oncology. Wojewodzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego)
Maroto Rey, Pablo (Institut d'Investigació Biomèdica Sant Pau)
Zieliński, Henryk (Clinical Urology. Military Institute of Medicine)
Villacampa, Felipe (Hospital Universitario 12 de Octubre (Madrid). Servicio de Urología)
Bigot, Pierre (Department of Urology. Centre Hospitalier Universitaire d'Angers)
Zoltan, Bajory (Szent-Györgyi Albert Klinikai Központ. Szegedi Tudomanyegyetem Altalanos Ovostudomanyi Kar Urologiai Klinika)
Parikh, Omi (Rosemere Cancer Centre. Royal Preston Hospital)
Vázquez Alba, David (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Jellvert, Åsa (Department of Oncology. Institute of Clinical Sciences. Sahlgrenska Academy. University of Gothenburg)
Flaskó, Tibor (Department of Urology. Medical School. University of Debrecen)
Gallardo, Eduard (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Ribal Caparrós, María José (Hospital Clínic i Provincial de Barcelona)
Purkalne, Gunta (Oncology Clinic. Pauls Stradins Clinical University Hospital)
Suenaert, Peter (Immunicum AB)
Karlsson-Parra, Alex (Department of Immunology. Genetics and Pathology. Section of Clinical Immunology. Uppsala University)
Ljungberg, Börje (Department of Surgical and Perioperative Sciences. Urology and Andrology. Umeå University)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design, setting, and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients). Outcome measurements and statistical analysis: The primary endpoints were 18-mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests. Results and limitations: The median OS was 35. 6 mo in the ILIXA/SUN arm versus 25. 3 mo in the SUN arm (hazard ratio 0. 73, 95% confidence interval 0. 42-1. 27; p = 0. 25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42. 2% (19/45), including three patients with complete response, versus 24. 0% (six/25) in the SUN arm (p = 0. 13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy. Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Allogeneic dendritic cells ; Ilixadencel ; Intratumoral administration ; Metastatic renal cell carcinoma ; Off the shelf ; Phase 2 trial ; Randomized ; Sunitinib
Publicat a:	European Urology Open Science, Vol. 40 (june 2022) , p. 38-45, ISSN 2666-1683

DOI: 10.1016/j.euros.2022.03.012
PMID: 35638086

8 p, 841.5 KB

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