1082MO - 5-year characterization of complete responses in patients with advanced melanoma who received nivolumab plus ipilimumab (NIVO+IPI) or NIVO alone

Background

5-year outcomes of patients (pts) with a CR to NIVO+IPI or NIVO alone and factors associated with continued CR or relapse are unknown. The current pooled analysis addresses these key questions, including a 12-mo CR landmark analysis used to decrease the time guarantee bias.

Methods

In this post hoc analysis, 5-yr data were pooled from the phase III CheckMate 066 and 067 studies and the phase II CheckMate 069 study of pts with treatment-naive, advanced melanoma. Analyzed pts received either the approved regimen of NIVO+IPI followed by NIVO monotherapy or NIVO monotherapy. Characteristics and outcomes of pts with a CR (by RECIST) were investigated, including 12-mo landmark survival analyses to determine the likelihood of being alive at 5-y among pts in CR by 12 mo (to mitigate the time guarantee bias).

Results

Minimum follow-up was 60 mo since randomization of the last pt in each study; pooled median mo of follow-up was 63 for NIVO+IPI (n=409) and 64 for NIVO (n=526). CRs were demonstrated in 96 (23%) NIVO+IPI pts and 102 (19%) NIVO pts; of CR pts alive at 5 yrs, 75/79 (95%) and 85/91 (93%) had not received subsequent systemic therapy. Baseline characteristics significantly associated with CR (Table) were M stage (NIVO+IPI), PD-L1 ≥ 5% (NIVO), normal lactate dehydrogenase (LDH; both) and fewer disease sites (both). Median duration of CR and median time to subsequent systemic therapy were not reached in either group. Median mo (Q1, Q3) to CR was 9.1 (2.8, 23.1) for NIVO+IPI and 11.8 (5.8, 26.5) for NIVO alone. In pts in CR at 12-mo, 5-y OS for NIVO+IPI and NIVO respectively was 85% and 86%; PFS was 84% and 82%.

Conclusions

NIVO+IPI- or NIVO-treated pts in CR at 12 mo have a high likelihood of being alive at 5 y even without subsequent systemic therapy. Several baseline pt characteristics were associated with CR duration. Factors associated with CR may differ for NIVO+IPI and NIVO alone. Biomarker analyses are ongoing. Table: 1082MO

ULN, upper limit of normal.

Clinical trial identification

NCT01721772; NCT01927419; NCT01844505.

Editorial acknowledgement

Writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

C. Robert: Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Biothera; Advisory/Consultancy: Ultimovacs. G.V. Long: Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Mass-Array; Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: Merck Sharp & Dohme Corp.; Advisory/Consultancy: Novartis; Advisory/Consultancy: OncoSec Medical Incorporated; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Roche; Advisory/Consultancy: Sandoz International GmbH. J. Larkin: Advisory/Consultancy, Research grant/Funding (self): Achilles Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb Company; Advisory/Consultancy: Eisai Co., Ltd.; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Ipsen Pharma; Advisory/Consultancy: Imugene Limited; Advisory/Consultancy: Incyte; Advisory/Consultancy: iOnctura; Advisory/Consultancy: Kymab; Advisory/Consultancy: Merck Sorono; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (self): Nektar; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy, Research grant/Funding (self): Pfizer Inc.; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Secarma; Advisory/Consultancy: Vitaccess; Advisory/Consultancy: Covance Inc.; Advisory/Consultancy, Research grant/Funding (self): Immunocore, Ltd.; Advisory/Consultancy: AVEO Pharmaceuticals, Inc.; Advisory/Consultancy: Pharmacyclics LLC. J.D. Wolchok: Advisory/Consultancy, Shareholder/Stockholder/Stock options: BeiGene; Shareholder/Stockholder/Stock options: Linneaus Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Arsenal-Caprion; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Sephora; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Apricity Therapeutics, Inc.; Advisory/Consultancy: Ascentage Pharma; Advisory/Consultancy: Astellas Pharma US, Inc.; Advisory/Consultancy: Bayer AG; Advisory/Consultancy: Celgene; Advisory/Consultancy: Chugai Pharmaceutical Co., Ltd.; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Elucida Oncology, Inc.; Advisory/Consultancy: F-star Biotechnology Limited; Advisory/Consultancy: Kyowa Kirin Co., Ltd.; Advisory/Consultancy: Merck and Co., Inc.; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Polynoma LLC; Advisory/Consultancy: PsiOxus Therapeutics; Advisory/Consultancy: Recepta Biopharma; Speaker Bureau/Expert testimony: Takara Bio Inc.; Advisory/Consultancy: Trieza Therapeutics; Advisory/Consultancy: Truvax Inc.; Advisory/Consultancy: Serametrix; Advisory/Consultancy: Surface; Advisory/Consultancy: Syndax Pharmaceuticals Inc.; Advisory/Consultancy: Syntalogic Pharmaceuticals, Inc. J.C. Hassel: Speaker Bureau/Expert testimony, Research grant/Funding (self), Payments for patient treatment in clinical trial: Bristol-Myers Squibb Company; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Sun Pharma. D. Schadendorf: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen Inc.; Honoraria (self), Advisory/Consultancy: Immunocore, Ltd.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Incyte; Honoraria (self), Advisory/Consultancy: 4SC; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre Group; Advisory/Consultancy: Sanofi/Regeneron; Travel/Accommodation/Expenses: Merck & Co., Inc.; Honoraria (self): Agenus Inc.; Honoraria (self): Array BioPharma; Honoraria (self): Pfizer; Honoraria (self): Philogen; Honoraria (self): Regeneron; Advisory/Consultancy: Nektar; Advisory/Consultancy: Sandoz. F.S. Hodi: Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck & Co., Inc.; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Licensing/Royalties: Novartis; Advisory/Consultancy: Takeda, Surface Pharmaceuticals, Compass Therapeutics, Verastem, Rheos, Amgen; Licensing/Royalties: Therapeutic Peptides Therapeutic Peptides Patent number: 9402905; Honoraria (self), Advisory/Consultancy: Genentech/Roche; Licensing/Royalties: Methods of Using Pembrolizumab and Trebananib Vaccine compositions and methods for restoring NKG2D pathway function against cancers Patent number: 10279021; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity Therapeutics; Honoraria (self), Advisory/Consultancy: Bayer; Advisory/Consultancy: Aduro Biotech; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: 7 Hills Pharma; Licensing/Royalties: Antibodies that bind to MHC class I polypeptide-related sequence a Patent number: 10106611; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Torque Pharmaceuticals; Licensing/Royalties: Anti-Galectin Antibody Biomarkers Predictive of Anti-Immune Checkpoint And Anti-Angiogenesis Responses Publication number: 20170343552; Honoraria (self), Advisory/Consultancy: Kairos Pharma; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Bicara Therapeutics; Honoraria (self), Advisory/Consultancy: Psioxus Therapeutics; Honoraria (self), Advisory/Consultancy: Pieris Pharmaceuticals; Licensing/Royalties: Methods for Treating MICA-Related Disorders (#20100111973); Research grant/Funding (institution), Licensing/Royalties: Tumour antigens and uses thereof (#7250291); Research grant/Funding (institution): Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603); Research grant/Funding (institution), Licensing/Royalties: Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407); Research grant/Funding (institution), Licensing/Royalties: Therapeutic peptides (#20160046716); Licensing/Royalties: Therapeutic Peptides (#20140004112); Licensing/Royalties: Therapeutic Peptides (#20170022275); Licensing/Royalties: Therapeutic Peptides (#20170008962); Advisory/Consultancy, Shareholder/Stockholder/Stock options: Pionyr Immunotherapeutics. C. Lebbé: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre Group. J-J. Grob: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi. K. Grossmann: Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Prometheus Biosciences; Advisory/Consultancy: Roche/Genentech. J. Wagstaff: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb Company. J. Chesney: Research grant/Funding (institution): Bristol-Myers Squibb Company. M.O. Butler: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Adaptimmune Therapeutics plc; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Immunocore, Ltd.; Advisory/Consultancy: EMD Serono. I. Márquez-Rodas: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre Group; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Incyte; Advisory/Consultancy: Merck Sorono; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bioncotech Therapeutics. A.C. Pavlick: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Jounce Therapeutics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Merck & Co., Inc.; Research grant/Funding (institution): Replimune Group Inc.; Research grant/Funding (institution): Iovance Biotherapeutics. S. Re: Full/Part-time employment: Bristol-Myers Squibb Company. M.A. Postow: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Incyte; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Aduro Biotech; Research grant/Funding (institution): RGenix; Research grant/Funding (institution): Infinity Pharmaceuticals; Research grant/Funding (institution): AstraZeneca. P.A. Ascierto: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Incyte; Advisory/Consultancy: MedImmune LLC; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax Pharmaceuticals, Inc.; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera Pharmaceuticals; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz International; Advisory/Consultancy: Immunocore, Ltd.; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco SpA; Advisory/Consultancy: Nektar; Advisory/Consultancy: Boehringer-Ingelheim; Travel/Accommodation/Expenses: Merck & Co., Inc. All other authors have declared no conflicts of interest.