LBA18_PR - Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC)
H-J.J. Lenz1, E. Van Cutsem2, M.L. Limon3, K.Y. Wong4, A. Hendlisz5, M. Aglietta6, P. Garcia-Alfonso7, B. Neyns8, G. Luppi9, D. Cardin10, T. Dragovich11, U. Shah12, A. Atasoy13, R. Postema14, Z. Boyd15, J-M. Ledeine16, M. Overman17, S. Lonardi18
1Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 2Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium, 3Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain, 4Medical Oncology, Westmead Hospital, Sydney, Australia, 5Internal Medicine, Institut Jules Bordet, Brussels, Belgium, 6Medical Oncology, Candiolo Cancer Institute and University of Torino Medical School, Candiolo, Italy, 7Medical Oncology, Hospital Gral Universitario Gregorio Marañon, Madrid, Spain, 8Medical Oncology, University Hospital Brussels, Brussels, Belgium, 9Oncology and Hematology, University Hospital of Modena, Modena, Italy, 10Department of Medicine, Vanderbilt – Ingram Cancer Center, Nashville, TN, USA, 11Medical Oncology and Hematology, Banner MD Anderson, Gilbert, AZ, USA, 12Hematology-Medical Onoclogy, Lehigh Valley Hospital, Allentown, PA, USA, 13R&D Oncology Clinical Development, Bristol-Myers Squibb Company, Princeton, NJ, USA, 14HEOR, Bristol-Myers Squibb Company, London, UK, 15Oncology Translational Medicine, Bristol-Myers Squibb Company, Princeton, NJ, USA, 16Biostatistics, Bristol-Myers Squibb Company, Princeton, NJ, USA, 17Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 18Medical Oncology, Istituto Oncologico Vento IOV-IRCSS, Padua, Italy
Background: In previously chemotherapy-treated patients with MSI-H/dMMR mCRC from the phase II CheckMate-142 trial, NIVO + low-dose IPI (1 mg/kg) provided durable clinical benefit (investigator-assessed [INV] objective response rate [ORR] 55%, median duration of response [DOR] not reached, 12-month overall survival [OS] rate 85%) and manageable safety. Here we report the first results of the efficacy and safety of NIVO + low-dose IPI as a first-line (1L) therapy for patients with MSI-H/dMMR mCRC from CheckMate-142.
Methods: Patients with no prior treatment for MSI-H/dMMR mCRC were treated with NIVO 3 mg/kg every 2 weeks (Q2W) + low-dose IPI every 6 weeks (Q6W) until disease progression. The primary endpoint was ORR (INV; RECIST v1.1).
Results: Of 45 patients, 51% were male and median age was 66 years. Median follow-up (time from first dose to data cut-off) was 13.8 months (range 9–19). The ORR and disease control rate (DCR) were 60% and 84%, respectively, with a 7% complete response rate (Table). Median DOR was not reached. At 12 months, progression-free survival (PFS) and OS rates were 77% and 83%, respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 16% of patients and 7% of patients had any grade TRAEs leading to discontinuation. Any grade select immune-mediated TRAEs affecting the hepatic (13%), gastrointestinal (11%), pulmonary (2%), and renal (2%) systems resolved in 100% of patients, while those affecting the skin (33%) and endocrine (24%) systems resolved in 45% and 60% of patients, respectively.
Conclusions: NIVO (Q2W) + low-dose IPI (Q6W) demonstrated robust and durable clinical benefit and was well-tolerated as a 1L treatment for MSI-H/dMMR mCRC. These results suggest that NIVO + low-dose IPI may represent a new treatment option for these patients.
Table. Efficacy and Safety
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NIVO + IPI (N = 45)
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ORRa, n (%) (95% CI)
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27 (60) (44–74)
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Best overall response, n (%) CR PR SD PD Not determined
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3 (7) 24 (53) 11 (24) 6 (13) 1 (2)
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DCRb, n (%) (95% CI)
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38 (84) (71–94)
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Median time to response, months (range)
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2.6 (1.2–13.8)
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Median DOR, months (95% CI)
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NR (11.5–NE)
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Median PFS, months (95% CI) 12-month rate, % (95% CI)
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NR (14.1–NE) 77 (62.0–87.2)
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Median OS, months (95% CI) 12-month rate, % (95% CI)
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NR (NE) 83 (67.6–91.7)
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TRAEs, n (%) Any grade Grade 3–4
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35 (78) 7 (16)
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TRAEs leading to discontinuation, n (%) Any grade Grade 3–4
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3 (7) 1 (2)
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aPatients with CR or PR divided by the number of treated patients bPatients with a CR, PR, or SD for ≥12 weeks divided by the number of treated patients CI = confidence interval; CR = complete response; NE = not estimable; NR = not reached; PD = progressive disease; PR = partial response; SD = stable disease
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Clinical trial identification: NCT02060188
Editorial Acknowledgement: Professional medical writing assistance and editorial assistance was provided by Tanmayi Mankame, PhD, and Christine Craig of Parexel International, funded by Bristol-Myers Squibb
Legal entity responsible for the study: Bristol-Myers Squibb
Funding: Bristol-Myers Squibb
Disclosure:
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H-J.J. Lenz: Honoraria: Bayer, Boehringer Ingelheim, Merck Serono, Roche; Consulting or Advisory Role: Bayer, Merck Serono, Pfizer, Roche; Travel, Accommodations, Expenses: Bayer, Merck Serono, Roche.
E. Van Cutsem: Grants: Amgen, Bayer, BMS, Boehringer, Celgene, Ipsen, Lilly, Merck, MSD, Novartis, Roche, Servier; Honoraria: Bayer, BMS, Celgene, Lilly, Novartis, Servier.
K.Y. Wong: Consultant/advisory role: Baxalta; Honoraria: Baxalta; Travel, accommodations, expenses: Roche.
M. Aglietta: Honoraria: Bristol-Myers Squibb; Consulting or Advisory Role: Bristol-Myers Squibb; Travel, Accommodations, Expenses: Bristol-Myers Squibb.
B. Neyns: Honoraria: BMS, Merck, Novartis, Roche; Consultant/Advisory: BMS, Merck, Novartis, Roche; Speakers' Bureau: Novartis; Research (Inst): Merck KGaA, Novartis, Pfizer; Travel: Amgen, BMS, Merck, Novartis, Roche.
D. Cardin: Consulting or Advisory Role: Merrimack, Raphael Pharmaceuticals; Research Funding (Inst.): Celgene, EMD Serono, Hoffman-LaRoche, Incyte, Oncolytics, Synta, BMS, Advaxis (Inst).
A. Atasoy: Employment: BMS.
R. Postema: BMS employee and shareholder.
Z. Boyd: Employment: Bristol Meyers Squibb; Stock and other ownership interests: Roche/Genentech, Bristol Meyers Squibb
J-M. Ledeine: Employment: Bristol-Myers Squibb; Stock and other ownership interests: Bristol-Myers Squibb.
M. Overman: Consulting or Advisory Role: Bristol-Myers Squibb, Merrimack, Roche/Genentech; Research Funding: Amgen, Bristol-Myers Squibb, Celgene, MedImmune, Merck, Roche.
S. Lonardi: Consulting or Advisory Role: Amgen, Bayer, Merck, Lilly; Speakers' Bureau: Lilly, Roche, BMS; Research Funding: Amgen.
All other authors have declared no conflicts of interest.
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