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

被引：39

作者：

Diab, Adi ^{[1
,26
]}

Gogas, Helen ^{[2
]}

Sandhu, Shahneen ^{[3
]}

Long, Georgina V. ^{[4
]}

Ascierto, Paolo A. ^{[5
]}

Larkin, James ^{[6
]}

Sznol, Mario ^{[7
]}

Franke, Fabio ^{[8
]}

Ciuleanu, Tudor E. ^{[9
]}

Pereira, Caio ^{[10
]}

Munoz Couselo, Eva ^{[11
]}

Bronzon Damian, Fernanda ^{[12
]}

Schenker, Michael ^{[13
]}

Perfetti, Aldo ^{[14
]}

Lebbe, Celeste ^{[15
]}

Quereux, Gaelle ^{[16
]}

Meier, Friedegund ^{[17
,18
]}

Curti, Brendan D. ^{[19
]}

Rojas, Carlos ^{[20
]}

Arriaga, Yull ^{[21
]}

Yang, Haisu ^{[21
]}

Zhou, Ming ^{[21
]}

Ravimohan, Shruthi ^{[22
]}

Statkevich, Paul ^{[23
]}

Tagliaferri, Mary A. ^{[24
]}

Khushalani, Nikhil I. ^{[25
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Melanoma Med Oncol Dept, Houston, TX USA

[2] Natl & Kapodistrian Univ Athens, Dept Med 1, Athens, Greece

[3] Univ Melbourne, Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia

[4] Univ Sydney, Royal North Shore & Mater Hosp, Melanoma Inst Australia, Sydney, NSW, Australia

[5] Ist Nazl Tumori IRCCS Fdn G Pascale, Melanoma Canc Immunotherapy & Dev Therapeut Dept, Naples, Italy

[6] Royal Marsden Hosp, Med Oncol, London, England

[7] Yale Univ, Sch Med, Yale Canc Ctr, Smilow Canc Hosp Yale New Haven,Med Oncol, New Haven, CT USA

[8] Oncosite Ctr Pesquisa Clin, Med Oncol, Ijui, Brazil

[9] Inst Prof Dr Ion Chiricuţa, Med Oncol, Cluj Napoca, Romania

[10] FdN Pio XII, Hosp Canc Barretos, Barretos, Brazil

[11] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Med Oncol, Barcelona, Spain

[12] Hosp Sao Lucas PUCRS, Porto Alegre, Brazil

[13] Univ Med & Pharm, Sf Nectarie Oncol Ctr, Craiova, Romania

[14] Clin Adventista Belgrano, Buenos Aires, Argentina

[15] Nord Univ Paris Cite, Univ Paris Cite, Canc Inst APHP, AP HP Dept Dermato Oncol & CIC,INSERM, Paris, France

[16] Nantes Univ Hosp, Dept Dermatol, CIC 1413, Cancero Dermatol CIC Biotherapie Nantes, Nantes, France

[17] Univ Canc Ctr Dresden, Skin Canc Ctr, Natl Ctr Tumor Dis, Dresden, Germany

[18] Univ Hosp Carl Gustav Carus, Dept Dermatol, Dresden, Germany

[19] Earle A Chiles Res Inst, Providence Canc Inst, Portland, OR 97213 USA

[20] Bradford Hill Clin Res Ctr, Med Oncol, Santiago, Chile

[21] Bristol Myers Squibb, Med Oncol, Princeton, NJ USA

[22] Bristol Myers Squibb, Translat Med, Princeton, NJ USA

[23] Bristol Myers Squibb, Clin Pharmacol & Pharmacometr, Princeton, NJ USA

[24] Nektar Therapeut, Clin Dev, San Francisco, CA USA

[25] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL USA

[26] Univ Texas MD Anderson Canc Ctr, Melanoma Med Oncol Dept, 1515 Holcombe Blvd, Houston, TX 77030 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2023年 / 41卷 / 30期

关键词：

IPILIMUMAB; SURVIVAL; EFFICACY; NKTR-214; CELLS;

D O I：

10.1200/JCO.23.00172

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEDespite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma.METHODSPatients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses.RESULTSIn 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02.CONCLUSIONThe PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.

引用

页码：4756 / +

页数：21

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