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)

Date

22 Oct 2018

Session

Proffered paper session - Gastrointestinal tumours, colorectal

Presenters

Heinz-Josef Lenz

Authors

H.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. Ledeine16, M. Overman17, S. Lonardi18

Author affiliations

  • 1 Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 2 Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, 3000 - Leuven/BE
  • 3 Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Seville/ES
  • 4 Medical Oncology, Westmead Hospital, 2145 - Sydney/AU
  • 5 Internal Medicine, Institut Jules Bordet, 1000 - Brussels/BE
  • 6 Medical Oncology, Candiolo Cancer Institute and University of Torino Medical School, 10060 - Candiolo/IT
  • 7 Medical Oncology, Hospital Gral Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 8 Medical Oncology, University Hospital Brussels, 1090 - Brussels/BE
  • 9 Oncology And Hematology, University Hospital of Modena, 41125 - Modena/IT
  • 10 Department Of Medicine, Vanderbilt – Ingram Cancer Center, 37232 - Nashville/US
  • 11 Medical Oncology And Hematology, Banner MD Anderson, 85234 - Gilbert/US
  • 12 Hematology-medical Onoclogy, Lehigh Valley Hospital, 18103 - Allentown/US
  • 13 R&d Oncology Clinical Development, Bristol-Myers Squibb Company, 08540 - Princeton/US
  • 14 Heor, Bristol-Myers Squibb Company, EC3N 2LS - London/GB
  • 15 Oncology Translational Medicine, Bristol-Myers Squibb Company, 08540 - Princeton/US
  • 16 Biostatistics, Bristol-Myers Squibb Company, 08540 - Princeton/US
  • 17 Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 18 Medical Oncology, Istituto Oncologico Vento IOV-IRCSS, 35128 - Padova/IT
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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
NIVO + IPI (N = 45)

ORRa, n (%)

(95% CI)

27 (60)

(44–74)

Best overall response, n (%)

CR

PR

SD

PD

Not determined

3 (7)

24 (53)

11 (24)

6 (13)

1 (2)

DCRb, n (%)

(95% CI)

38 (84)

(71–94)
Median time to response, months (range) 2.6 (1.2–13.8)
Median DOR, months (95% CI) NR (11.5–NE)

Median PFS, months (95% CI)

12-month rate, % (95% CI)

NR (14.1–NE)

77 (62.0–87.2)

Median OS, months (95% CI)

12-month rate, % (95% CI)

NR (NE)

83 (67.6–91.7)

TRAEs, n (%)

Any grade

Grade 3–4

35 (78)

7 (16)

TRAEs leading to discontinuation, n (%)

Any grade

Grade 3–4

3 (7)

1 (2)

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

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.

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