LBA1_PR - Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung canc...

Date 11 April 2019
Event European Lung Cancer Congress 2019
Session ESMO-IASLC Best Abstracts
Topics Small Cell Lung Cancer
Immunotherapy
Presenter Taofeek Owonikoko
Citation Annals of Oncology (2019) 30 (suppl_2): ii77-ii80. 10.1093/annonc/mdz094
Authors T.K. Owonikoko1, H.R. Kim2, R. Govindan3, N. Ready4, M. Reck5, S. Peters6, S.R. Dakhil7, A. Navarro8, J. Rodriguez-Cid9, M. Schenker10, J.S. Lee11, V. Gutierrez12, I. Percent13, D. Morgensztern14, J. Fairchild15, C. Baudelet15, K. Park16
  • 1Winship Cancer Institute of Emory University, 30322 - Atlanta/US
  • 2Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 3Washington University Medical School, 63110 - St. Louis/US
  • 4Duke University Medical Center, Durham/US
  • 5Lungenclinic Grosshansdorf, Airway Research Center North (arcn), German Center for Lung Research (DZL), Grosshansdorf/DE
  • 6Multidisciplinary Oncology Centre, Centre Hospitalier Universitaire Vaudois, Lausanne/CH
  • 7Cancer Center of Kansas, Wichita/US
  • 8Vall d'Hebron University Hospital, Barcelona/ES
  • 9Centro Oncológico, Médica Sur, Mexico City/MX
  • 10Centrul de Oncologie Sf Nectarie, Craiova/RO
  • 11Seoul National University Bundang Hospital, Seoul/KR
  • 12Hospital Carlos Haya de Malaga, Malaga/ES
  • 13Florida Cancer Specialists, Punta Gorda/US
  • 14Washington University Medical School, St. Louis/US
  • 15Bristol-Myers Squibb, Princeton/US
  • 16Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR

Background

In pts with ED-SCLC, response rates to 1L platinum-based chemo are high but lack durability. Treatments (txs) that prolong response duration and improve survival are needed. CheckMate 451 (NCT02538666) is a global, double-blind, phase 3 study of nivo+ipi or nivo vs pbo as maintenance therapy in pts with ED-SCLC who did not progress on 1L platinum-based chemo.

Methods

Pts (N = 834) with ED-SCLC, ECOG performance status (PS) ≤ 1 and response or stable disease after 4 cycles of 1L platinum-based chemo were randomized 1:1:1 (3–9 weeks from last dose of 1L chemo or 3–11 weeks for pts who received prophylactic cranial irradiation [PCI]) to nivo 1 mg/kg + ipi 3 mg/kg Q3W intravenously (IV; 4 doses followed by nivo 240 mg Q2W IV; n = 279), nivo 240 mg Q2W IV (n = 280), or pbo (n = 275), stratified by PS, sex and prior PCI. Pts were treated up to 2 years or until progression or unacceptable toxicity. Primary endpoint was overall survival (OS) for nivo+ipi vs pbo. Secondary endpoints included OS for nivo vs pbo and progression-free survival (PFS) per blinded independent central review for nivo+ipi vs pbo and nivo vs pbo.

Results

Minimum study follow-up was 9 months. Baseline characteristics were balanced between arms. OS was not significantly prolonged with nivo+ipi vs pbo (HR, 0.92; 95% CI 0.75–1.12; P = 0.3693). OS was also not prolonged for nivo vs pbo (HR, 0.84; 95% CI 0.69–1.02), although not formally tested due to statistical hierarchy. PFS HRs vs pbo were: nivo+ipi, 0.72 (0.60–0.87); nivo, 0.67 (0.56–0.81). Rates of all-grade (grade 3–4) tx-related adverse events were: nivo+ipi, 86% (52%); nivo, 61% (12%); pbo, 50% (8%). Rates of discontinuation due to tx toxicity were: nivo+ipi, 31%; nivo, 9%; pbo, <1%. Tx-related deaths were: nivo+ipi, 7 (2.5%); nivo, 1 (<1%); pbo, 1 (<1%).

Conclusions

In CheckMate 451, maintenance therapy with nivo+ipi (primary endpoint) or nivo did not prolong OS vs pbo for ED-SCLC patients who did not progress on 1L chemo. Safety profiles of nivo+ipi and nivo were consistent with previous reports at this dose/schedule in SCLC.

Clinical trial identification

NCT02538666; Release date: 2 September 2015.

Editorial acknowledgement

Writing and editorial assistance was provided by Cristina Tomas, PhD, of Caudex and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

T.K. Owonikoko: Research support: AbbVie, Adaptimmune, Amgen, AstraZeneca, Bristol-Myers Squibb, Corvus, G1 Therapeutics, Novartis, Pfizer, Regeneron/Sanofi; Advisory board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly/Armo, PharmaMar, Xcovery; IRC/DSMB: EMD Serono, Roche/Genentech; Co-founder: Cambium Oncology. H.R. Kim: Speakers bureau, honoraria: AstraZeneca, ONO/Bristol-Myers Squibb; Consultant: Roche. R. Govindan: Consultant/advisory committees: AbbVie, Adaptimmune, AstraZeneca, Celgene, Ignyta, Inivata, Merck, Nektar, Pfizer, Roche. N. Ready: Advisor: AbbVie, G1 therapeutics, Merck, Novartis; Advisor/speaker: Bristol-Myers Squibb, Celgene; Education: AstraZeneca, EMD Serrano, Tesaro. M. Reck: Honoraria for lectures and consultancy: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Peters: Honoraria, education grants, consultancy, attended advisory boards, and/or provided lectures: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda. A. Navarro: Advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Safety committee member: Oryzon Genomics; Travel support: Boehringer Ingelheim, Pfizer. J. Rodriguez-Cid: Investigational resources: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, MSD, Novartis, Roche, Takeda; Advisory role: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, MSD, Novartis, Pfizer, Roche, Takeda; Speaker role: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda. M. Schenker: For clinical trial participation (as PI/SI) my institution and I have received funds from: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bioven, Bristol-Myers Squibb, Eisai, Eli Lilly, Gilead, Merck Serono, MSD, Mylan, Nano Carrier, Novartis, Pfizer, PharmaMar, Regeneron, Roche, Samsung D. Morgensztern: Advisory board: AbbVie, Bristol-Myers Squibb, PharmaMar, Takeda. J. Fairchild: Stock ownership: Bristol-Myers Squibb. C. Baudelet: Employee: Bristol-Myers Squibb. K. Park: Advisor: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Abstract

Background

In pts with ED-SCLC, response rates to 1L platinum-based chemo are high but lack durability. Treatments (txs) that prolong response duration and improve survival are needed. CheckMate 451 (NCT02538666) is a global, double-blind, phase 3 study of nivo+ipi or nivo vs pbo as maintenance therapy in pts with ED-SCLC who did not progress on 1L platinum-based chemo.

Methods

Pts (N = 834) with ED-SCLC, ECOG performance status (PS) ≤ 1 and response or stable disease after 4 cycles of 1L platinum-based chemo were randomized 1:1:1 (3–9 weeks from last dose of 1L chemo or 3–11 weeks for pts who received prophylactic cranial irradiation [PCI]) to nivo 1 mg/kg + ipi 3 mg/kg Q3W intravenously (IV; 4 doses followed by nivo 240 mg Q2W IV; n = 279), nivo 240 mg Q2W IV (n = 280), or pbo (n = 275), stratified by PS, sex and prior PCI. Pts were treated up to 2 years or until progression or unacceptable toxicity. Primary endpoint was overall survival (OS) for nivo+ipi vs pbo. Secondary endpoints included OS for nivo vs pbo and progression-free survival (PFS) per blinded independent central review for nivo+ipi vs pbo and nivo vs pbo.

Results

Minimum study follow-up was 9 months. Baseline characteristics were balanced between arms. OS was not significantly prolonged with nivo+ipi vs pbo (HR, 0.92; 95% CI 0.75–1.12; P = 0.3693). OS was also not prolonged for nivo vs pbo (HR, 0.84; 95% CI 0.69–1.02), although not formally tested due to statistical hierarchy. PFS HRs vs pbo were: nivo+ipi, 0.72 (0.60–0.87); nivo, 0.67 (0.56–0.81). Rates of all-grade (grade 3–4) tx-related adverse events were: nivo+ipi, 86% (52%); nivo, 61% (12%); pbo, 50% (8%). Rates of discontinuation due to tx toxicity were: nivo+ipi, 31%; nivo, 9%; pbo, <1%. Tx-related deaths were: nivo+ipi, 7 (2.5%); nivo, 1 (<1%); pbo, 1 (<1%).

Conclusions

In CheckMate 451, maintenance therapy with nivo+ipi (primary endpoint) or nivo did not prolong OS vs pbo for ED-SCLC patients who did not progress on 1L chemo. Safety profiles of nivo+ipi and nivo were consistent with previous reports at this dose/schedule in SCLC.

Clinical trial identification

NCT02538666; Release date: 2 September 2015.

Editorial acknowledgement

Writing and editorial assistance was provided by Cristina Tomas, PhD, of Caudex and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

T.K. Owonikoko: Research support: AbbVie, Adaptimmune, Amgen, AstraZeneca, Bristol-Myers Squibb, Corvus, G1 Therapeutics, Novartis, Pfizer, Regeneron/Sanofi; Advisory board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly/Armo, PharmaMar, Xcovery; IRC/DSMB: EMD Serono, Roche/Genentech; Co-founder: Cambium Oncology. H.R. Kim: Speakers bureau, honoraria: AstraZeneca, ONO/Bristol-Myers Squibb; Consultant: Roche. R. Govindan: Consultant/advisory committees: AbbVie, Adaptimmune, AstraZeneca, Celgene, Ignyta, Inivata, Merck, Nektar, Pfizer, Roche. N. Ready: Advisor: AbbVie, G1 therapeutics, Merck, Novartis; Advisor/speaker: Bristol-Myers Squibb, Celgene; Education: AstraZeneca, EMD Serrano, Tesaro. M. Reck: Honoraria for lectures and consultancy: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Peters: Honoraria, education grants, consultancy, attended advisory boards, and/or provided lectures: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda. A. Navarro: Advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Safety committee member: Oryzon Genomics; Travel support: Boehringer Ingelheim, Pfizer. J. Rodriguez-Cid: Investigational resources: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, MSD, Novartis, Roche, Takeda; Advisory role: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, MSD, Novartis, Pfizer, Roche, Takeda; Speaker role: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda. M. Schenker: For clinical trial participation (as PI/SI) my institution and I have received funds from: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bioven, Bristol-Myers Squibb, Eisai, Eli Lilly, Gilead, Merck Serono, MSD, Mylan, Nano Carrier, Novartis, Pfizer, PharmaMar, Regeneron, Roche, Samsung D. Morgensztern: Advisory board: AbbVie, Bristol-Myers Squibb, PharmaMar, Takeda. J. Fairchild: Stock ownership: Bristol-Myers Squibb. C. Baudelet: Employee: Bristol-Myers Squibb. K. Park: Advisor: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.