Pembrolizumab Plus Enfortumab Vedotin in Collecting Duct and Renal Medullary Carcinoma

Summary

This is a single-arm, monocentric, phase II trial, enrolling patients with histological diagnosis of collecting duct carcinoma and renal medullary carcinoma with locally advanced or metastatic disease who will be treated with Pembrolizumab plus Enfortumab Vedotin. Approximately, 23 patients will be enrolled. At screening, pre-existing archival primary and metastatic FFPE tumor specimen will be collected and submitted for central pathology review and translational analysis. All participants will undergo baseline screening imaging for clinical staging. Patients will be treated with Pembrolizumab q21 plus Enfortumab Vedotin 1,8q21 for 3 cycles (3 infusion of Pembrolizumab and 6 infusion of Enfortumab Vedotin) then radiological imaging will be repeated and patients with SD, PR or CR will continue pembrolizumab until disease progression, unacceptable toxicities or completion of treatment (17 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. Patients who will experience progressive disease during pembrolizumab monotherapy treatment could restart Enfortumab Vedotin. The study will also involve collection of a blood sample taken at the commencement of treatment, at the first cycle, after cycle 3 and at the end of treatment or progression of disease, to be used for research purposes.

Timeline

Start

2025-05-30

Primary completion

2027-10

Completion

2029-05

Publications

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• Results Pagani F, Colecchia M, Sepe P, Apollonio G, Claps M, Verzoni E, de Braud F, Procopio G. Collecting ducts carcinoma: An orphan disease. Literature overview and future perspectives. Cancer Treat Rev. 2019 Sep;79:101891. doi: 10.1016/j.ctrv.2019.101891. Epub 2019 Aug 27.
• Results Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, Raitano A, Nadell R, Liu W, Lortie DR, Capo L, Verlinsky A, Leavitt M, Malik F, Avina H, Guevara CI, Dinh N, Karki S, Anand BS, Pereira DS, Joseph IB, Donate F, Morrison K, Stover DR. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016 May 15;76(10):3003-13. doi: 10.1158/0008-5472.CAN-15-1313. Epub 2016 Mar 24.
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• Results Takai Y, Ikeda W, Ogita H, Rikitake Y. The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin. Annu Rev Cell Dev Biol. 2008;24:309-42. doi: 10.1146/annurev.cellbio.24.110707.175339.
• Results Rikitake Y, Takai Y. Interactions of the cell adhesion molecule nectin with transmembrane and peripheral membrane proteins for pleiotropic functions. Cell Mol Life Sci. 2008 Jan;65(2):253-63. doi: 10.1007/s00018-007-7290-9.
• Results Wahler D, Reymond JL. Novel methods for biocatalyst screening. Curr Opin Chem Biol. 2001 Apr;5(2):152-8. doi: 10.1016/s1367-5931(00)00184-8.
• Results Takai Y, Miyoshi J, Ikeda W, Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol. 2008 Aug;9(8):603-15. doi: 10.1038/nrm2457.
• Results Fabre-Lafay S, Monville F, Garrido-Urbani S, Berruyer-Pouyet C, Ginestier C, Reymond N, Finetti P, Sauvan R, Adelaide J, Geneix J, Lecocq E, Popovici C, Dubreuil P, Viens P, Goncalves A, Charafe-Jauffret E, Jacquemier J, Birnbaum D, Lopez M. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer. 2007 May 2;7:73. doi: 10.1186/1471-2407-7-73.
• Results Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, Baranda J, Lang J, Plimack ER, Sangha R, Heath EI, Merchan J, Quinn DI, Srinivas S, Milowsky M, Wu C, Gartner EM, Zuo P, Melhem-Bertrandt A, Petrylak DP. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol. 2020 Apr 1;38(10):1041-1049. doi: 10.1200/JCO.19.02044. Epub 2020 Feb 7.
• Results Gargiuli C, Sepe P, Tessari A, Sheetz T, Colecchia M, de Braud FGM, Procopio G, Sensi M, Verzoni E, Dugo M. Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma. Cancers (Basel). 2021 Jun 10;13(12):2903. doi: 10.3390/cancers13122903.
• Results Buti S, Trentini F, Sepe P, Claps M, Isella L, Verzoni E, Procopio G. BONSAI-2 study: Nivolumab as therapeutic option after cabozantinib failure in metastatic collecting duct carcinoma patients. Tumori. 2023 Aug;109(4):418-423. doi: 10.1177/03008916221141483. Epub 2022 Dec 6.
• Results Procopio G, Verzoni E, Iacovelli R, Colecchia M, Torelli T, Mariani L. Is there a role for targeted therapies in the collecting ducts of Bellini carcinoma? Efficacy data from a retrospective analysis of 7 cases. Clin Exp Nephrol. 2012 Jun;16(3):464-7. doi: 10.1007/s10157-012-0589-3. Epub 2012 Jan 26.
• Results Mennitto A, Verzoni E, Peverelli G, Alessi A, Procopio G. Management of Metastatic Collecting Duct Carcinoma: An Encouraging Result in a Patient Treated With Cabozantinib. Clin Genitourin Cancer. 2018 Jun;16(3):e521-e523. doi: 10.1016/j.clgc.2018.03.010. Epub 2018 Mar 27. No abstract available.

Drugs

Indications