Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09)

Author:

Tannir Nizar M.1ORCID,Formiga Maria Nirvana2ORCID,Penkov Konstantin3,Kislov Nikolay4ORCID,Vasiliev Aleksandr5,Gunnar Skare Nils6,Hong Walter7,Dai Stanley7ORCID,Tang Lily7ORCID,Qureshi Anila8,Zalevsky Jonathan7,Tagliaferri Mary A.7ORCID,George Daniel9ORCID,Agarwal Neeraj10ORCID,Pal Sumanta11ORCID,Marathe Omkar,Curti Brendan,Hussain Arif,Bilen Mehmet Asim,Pal Sumanta Kumar,Tannir Nizar M.,Uchio Edward,Nair Seresh,Zuniga Richard,Clark William,Agarwal Neeraj,Tester William,Franks Emily,Patel Kamal,Barata Pedro C.,Sharma Janaki Neela,Radhi Saba,Joshi Monika,Parnis Francis,Gurney Howard,Zielinski Robert,Guminski Alexander,Campbell David,Fu Simon,Vasiliev Alexandr,Kopyltsov Evgeniy,Penkov Konstantin,Gladkov Oleg,Perlin Dmitry,Nosov Dmitry,Kheifets Vladimir,Lifirenko Igor,Varlamov Sergey,Kislov Nikolay,Karyakin Oleg,Zhiltsova Elena,Fadeeva Natalia,Kahl Susana,Kowalyszyn Rubén,Pilnik Norma,Amuchastegui Valeria Agostinetti,Pastor Andrea,Vázquez Rocío,Lucas Kaen Diego,Brown Arnold Mario Alfredo,Palazzo Felipe Salvador,Jarchum Gustavo,Pfluger Yanina,Salinas Jorge,Re Juan Pablo,Jobim de Azevedo Sergio,Fay Andre Poisi,Kussumoto Celio,Rocha Roberto Odebrecht,Ferreira Ubirajara,Jose da Fonseca Vinholes Jeferson,Girotto Gustavo Colagiovanni,Lopes dos Santos Victor Marcondes,Nirvana da Cruz Formiga Maria,Zereu Manuela,de Cassia Costamilan Rita,D'Almeida Preto Daniel,Holanda Soares Joao Paulo,Skare Nils Gunnar,Kann Ariel Galapo,Guimaraes Rodrigo Cunha,Patricia dos Santos Martins Suelen,Azambuja Alan Arrieira,Lopes Nogueira Jose Alberto,Brust Leandro,Martins Segalla Jose Getulio,de Liz Vassen Schurmann Maite,Franke Fabio Andre,Sales Silvio Correia,de Castro Monteiro Daniel,Marinho dos Santos Gisele,Cesar de Andrade Mota Augusto,Martinez Lira Jose Luis,Bernal Eduardo Tellez,Bailon Denisse Anorve,Alvarez Ivan Martinez,Soto Francisco Medina,Acevedo Zanabria Carmen Laura,Torrejon Alejandro Figueroa,Zorrilla Silvera Jose David,Salas Rojas Renzo Mauricio,Panay Sergio,Acevedo Gaete Alejandro Andres,Gorena Palominos Mario Alberto,Salman Boghikian Pamela Victoria,de las Nieves Loredo Fort Eugenia,Orellana Ulunque Eric Armando,Hornig Epple Valentina Isabel,Elqueta Pinochet Sergio Fabian,Peng Thomas Soh I.,Sing Ng Quan,Crilley Pamela,Ghani Muhammad

Affiliation:

1. The University of Texas MD Anderson Cancer Center, Houston, TX

2. A.C. Camargo Cancer Center, São Paulo, Brazil

3. Private Medical Institution Euromedservice, St Petersburg, Russian Federation

4. Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation

5. Railway Clinical Hospital JSC RZhD, St Petersburg, Russian Federation

6. Paraná Institute of Oncology, and Hospital Erasto Gaertner, Curitiba, Brazil

7. Nektar Therapeutics, San Francisco, CA

8. Bristol Myers Squibb, Princeton, NJ

9. Duke Cancer Institute, Durham, NC

10. Huntsman Cancer Hospital, Salt Lake City, UT

11. City of Hope, Duarte, CA

Abstract

PURPOSE Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8+ T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment. The open-label, phase III randomized controlled PIVOT-09 trial investigated the efficacy and safety of BEMPEG plus nivolumab (NIVO) as first-line treatment for advanced/metastatic clear cell renal cell carcinoma (ccRCC) with intermediate-/poor-risk disease. METHODS Patients with previously untreated advanced/metastatic ccRCC were randomly assigned (1:1) to BEMPEG plus NIVO, or investigator's choice of tyrosine kinase inhibitor (TKI; sunitinib or cabozantinib). Coprimary end points were objective response rate (ORR) by blinded independent central review and overall survival (OS) in patients with International Metastatic RCC Database Consortium (IMDC) intermediate-/poor-risk disease. RESULTS Overall, 623 patients were randomly assigned to BEMPEG plus NIVO (n = 311) or TKI (n = 312; sunitinib n = 225, cabozantinib n = 87), of whom 514 (82.5%) had IMDC intermediate-/poor-risk disease. In patients with IMDC intermediate-/poor-risk disease, ORR with BEMPEG plus NIVO versus TKI was 23.0% (95% CI, 18.0 to 28.7) versus 30.6% (95% CI, 25.1 to 36.6; difference, –7.7 [95% CI, –15.2 to –0.2]; P = .0489), and median OS was 29.0 months versus not estimable (hazard ratio, 0.82 [95% CI, 0.61 to 1.10]; P = .192), respectively. More frequent all-grade treatment-related adverse events (TRAEs) with BEMPEG plus NIVO versus TKI included pyrexia (32.6% v 2.0%) and pruritus (31.3% v 8.8%). Grade 3/4 TRAEs were less frequent with BEMPEG plus NIVO (25.8%) versus TKI (56.5%). CONCLUSION First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI.

Publisher

American Society of Clinical Oncology (ASCO)

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