Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10)

被引：0

作者：

Siefker-Radtke, Arlene O. ^{[1
]}

Huddart, Robert A. ^{[2
]}

Bilen, Mehmet A. ^{[3
]}

Balar, Arjun ^{[4
]}

Castellano, Daniel ^{[5
]}

Sridhar, Srikala S. ^{[6
]}

De Giorgi, Ugo ^{[7
]}

Penkov, Konstantin ^{[8
]}

Vasiliev, Aleksandr ^{[9
]}

Peer, Avivit ^{[10
]}

Jarvinen, Riikka ^{[11
]}

Harputluoglu, Hakan ^{[12
]}

Koshkin, Vadim S. ^{[13
]}

Poushnejad, Shermeen ^{[14
]}

Wang, Tianhua ^{[14
]}

Qureshi, Anila ^{[15
]}

Tagliaferri, Mary A. ^{[14
]}

Zalevsky, Jonathan ^{[14
]}

Loriot, Yohann ^{[16
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[2] Royal Marsden NHS Fdn Trust, Surrey, England

[3] Emory Univ, Winship Canc Inst, Atlanta, GA USA

[4] NYU Langone Hlth, Perlmutter Canc Ctr, New York, NY USA

[5] Hosp Univ 12 Octubre, Madrid, Spain

[6] Princess Margaret Canc Ctr, Toronto, ON, Canada

[7] Ist Romagnolo Studio Tumori IRST Dino Amadori, Meldola, Emilia Romagna, Italy

[8] Private Med Inst Euromedserv, St Petersburg, Russia

[9] Railway Clin Hosp JSC RZhD, St Petersburg, Russia

[10] Rambam Hlth Care Campus, Haifa, Israel

[11] Helsinki Univ Hosp, Helsinki, Finland

[12] Inonu Univ, Malatya, Turkiye

[13] Univ Calif San Francisco, San Francisco, CA USA

[14] Nektar Therapeut, San Francisco, CA USA

[15] Bristol Myers Squibb, Princeton, NJ USA

[16] Inst Gustave Roussy, Paris, France

来源：

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS | 2025年 / 43卷 / 05期

关键词：

Combination; IL-2; Immunotherapy; Urothelial carcinoma; OPEN-LABEL; CHEMOTHERAPY; MULTICENTER; PEMBROLIZUMAB; ATEZOLIZUMAB; EFFICACY; NKTR-214;

D O I：

10.1016/j.urolonc.2024.09.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma. Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment. Patients received BEMPEG plus NIVO were administered intravenously every 3 weeks for <= 2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) in patients with low programmed death ligand-1 (PD-L1) expression. Secondary endpoints included ORR and duration of response in the overall population. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. Results: One hundred and eighty-eight patients were enrolled; 123 patients were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS >= 10), and 6 had PD-L1 status unknown (3.2%). ORR per blinded independent central review in patients with PD-L1-low tumors was 17.9% (95% confidence interval [CI] 11.6-25.8) while in all treated patients was 19.7% (95% CI 14.3-26.1). Median PFS and OS in the overall population were 3.0 months and 12.6 months, respectively. BEMPEG plus NIVO combination was well tolerated, with a safety profile similar to previously reported trials; no new or unexpected safety signals were reported. Conclusions: BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression. (c) 2024 Published by Elsevier Inc.

引用

页码：1 / 9

页数：9

共 27 条

[1] Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial [J].

Albiges, Laurence ;

Tannir, Nizar M. ;

Burotto, Mauricio ;

McDermott, David ;

Plimack, Elizabeth R. ;

Barthelemy, Philippe ;

Porta, Camillo ;

Powles, Thomas ;

Donskov, Frede ;

George, Saby ;

Kollmannsberger, Christian K. ;

Gurney, Howard ;

Grimm, Marc-Oliver ;

Tomita, Yoshihiko ;

Castellano, Daniel ;

Rini, Brian, I ;

Choueiri, Toni K. ;

Saggi, Shruti Shally ;

McHenry, M. Brent ;

Motzer, Robert J. .

ESMO OPEN, 2020, 5 (06)

[2]

[Anonymous], 2023, BRISTOL MYERS SQUIBB

[3]

[Anonymous], NCCN CLIN PRACTICE G

[4] Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial [J].

Balar, Arjun V. ;

Galsky, Matthew D. ;

Rosenberg, Jonathan E. ;

Powles, Thomas ;

Petrylak, Daniel P. ;

Bellmunt, Joaquim ;

Loriot, Yohann ;

Necchi, Andrea ;

Hoffman-Censits, Jean ;

Perez-Gracia, Jose Luis ;

Dawson, Nancy A. ;

van der Heijden, Michiel S. ;

Dreicer, Robert ;

Srinivas, Sandy ;

Retz, Margitta M. ;

Joseph, Richard W. ;

Drakaki, Alexandra ;

Vaishampayan, Ulka N. ;

Sridhar, Srikala S. ;

Quinn, David I. ;

Duran, Ignacio ;

Shaffer, David R. ;

Eigl, Bernhard J. ;

Grivas, Petros D. ;

Yu, Evan Y. ;

Li, Shi ;

Kadel, Edward E., III ;

Boyd, Zachary ;

Bourgon, Richard ;

Hegde, Priti S. ;

Mariathasan, Sanjeev ;

Thastrom, AnnChristine ;

Abidoye, Oyewale O. ;

Fine, Gregg D. ;

Bajorin, Dean F. .

LANCET, 2017, 389 (10064) :67-76

[5] A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel 1L2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors [J].

Bentebibel, Salah-Eddine ;

Hurwitz, Michael E. ;

Bernatchez, Chantale ;

Haymaker, Cara ;

Hudgens, Courtney W. ;

Kluger, Harriet M. ;

Tetzlaff, Michael T. ;

Tagliaferri, Mary A. ;

Zalevsky, Jonathan ;

Hoch, Ute ;

Fanton, Christie ;

Aung, Sandra ;

Hwu, Patrick ;

Curti, Brendan D. ;

Tannir, Nizar M. ;

Sznol, Mario ;

Diab, Adi .

CANCER DISCOVERY, 2019, 9 (06) :711-721

[6] Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy. [J].

Bernatchez, Chantale ;

Haymaker, Cara L. ;

Hurwitz, Michael E. ;

Kluger, Harriet M. ;

Tetzlaff, Michael T. ;

Jackson, Natalie ;

Gergel, Ivan ;

Tagliaferri, Mary Ann ;

Zalevsky, Jonathan ;

Hoch, Ute ;

Fanton, Christie ;

Iacucci, Ernesto ;

Aung, Sandra ;

Imperiale, Michael ;

Liao, Ej ;

Bentebibel, Salah E. ;

Tannir, Nizar M. ;

Hwu, Patrick ;

Sznol, Mario ;

Diab, Adi .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35

[7] Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy [J].

Charych, Deborah ;

Khalili, Samira ;

Dixit, Vidula ;

Kirk, Peter ;

Chang, Thomas ;

Langowski, John ;

Rubas, Werner ;

Doberstein, Stephen K. ;

Eldon, Michael ;

Hoch, Ute ;

Zalevsky, Jonathan .

PLOS ONE, 2017, 12 (07)

[8] NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models [J].

Charych, Deborah H. ;

Hoch, Ute ;

Langowski, John L. ;

Lee, Steve R. ;

Addepalli, Murali K. ;

Kirk, Peter B. ;

Sheng, Dawei ;

Liu, Xiaofeng ;

Sims, Paul W. ;

VanderVeen, Laurie A. ;

Ali, Cherie F. ;

Chang, Thomas K. ;

Konakova, Marina ;

Pena, Rhoneil L. ;

Kanhere, Rupesh S. ;

Kirksey, Yolanda M. ;

Ji, Chunmei ;

Wang, Yujun ;

Huang, Jicai ;

Sweeney, Theresa D. ;

Kantak, Seema S. ;

Doberstein, Stephen K. .

CLINICAL CANCER RESEARCH, 2016, 22 (03) :680-690

[9] Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results [J].

Diab, Adi ;

Gogas, Helen ;

Sandhu, Shahneen ;

Long, Georgina V. ;

Ascierto, Paolo A. ;

Larkin, James ;

Sznol, Mario ;

Franke, Fabio ;

Ciuleanu, Tudor E. ;

Pereira, Caio ;

Munoz Couselo, Eva ;

Bronzon Damian, Fernanda ;

Schenker, Michael ;

Perfetti, Aldo ;

Lebbe, Celeste ;

Quereux, Gaelle ;

Meier, Friedegund ;

Curti, Brendan D. ;

Rojas, Carlos ;

Arriaga, Yull ;

Yang, Haisu ;

Zhou, Ming ;

Ravimohan, Shruthi ;

Statkevich, Paul ;

Tagliaferri, Mary A. ;

Khushalani, Nikhil I. .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (30) :4756-+

[10] Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma [J].

Diab, Adi ;

Tykodi, Scott S. ;

Daniels, Gregory A. ;

Maio, Michele ;

Curti, Brendan D. ;

Lewis, Karl D. ;

Jang, Sekwon ;

Kalinka, Ewa ;

Puzanov, Igor ;

Spira, Alexander, I ;

Cho, Daniel C. ;

Guan, Shanhong ;

Puente, Erika ;

Tuan Nguyen ;

Hoch, Ute ;

Currie, Sue L. ;

Lin, Wei ;

Tagliaferri, Mary A. ;

Zalevsky, Jonathan ;

Sznol, Mario ;

Hurwitz, Michael E. .

JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (26) :2914-+

← 1 2 3 →