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CNS tumours

3698 - Nivolumab (nivo) in Combination With Radiotherapy (RT) ± Temozolomide (TMZ): Updated Safety Results From CheckMate 143 in Pts With Methylated or Unmethylated Newly Diagnosed Glioblastoma (GBM)

Date

08 Sep 2017

Session

CNS tumours

Topics

Immunotherapy;  Surgical Oncology;  Radiation Oncology;  Prostate Cancer;  Central Nervous System Malignancies

Presenters

Michael Lim

Citation

Annals of Oncology (2017) 28 (suppl_5): v109-v121. 10.1093/annonc/mdx366

Authors

M. Lim1, A. Omuro2, G. Vlahovic3, D.A. Reardon4, S. Sahebjam5, T. Cloughesy6, J. Baehring7, N. Butowski8, V. Potter9, R. Zwirtes9, P. Paliwal9, M. Carleton9, J. Sampson3, A.A. Brandes10

Author affiliations

  • 1 Metastatic Brain Tumor Center, Johns Hopkins University School of Medicine, - - Baltimore/US
  • 2 Neurology, Memorial Sloan Kettering Cancer Center, New York/US
  • 3 The Preston Robert Tisch Brain Tumor Center At Duke, Duke University Medical Center, 27710 - Durham/US
  • 4 Center For Neuro-oncology, Dana-Farber Cancer Institute and Harvard University School of Medicine, Boston/US
  • 5 Oncology, H. Lee Moffitt Cancer Center University of South Florida, 33612 - Tampa/US
  • 6 Neurology-oncology, University of California Los Angeles, Los Angeles/US
  • 7 Neurology, Yale School of Medicine, New Haven/US
  • 8 Department Of Neurological Surgery, University of California, San Francisco, San Francisco/US
  • 9 Oncology, Bristol-Myers Squibb, Princeton/US
  • 10 Neurology, AUSL-IRCCS Institute of Neurological Sciences, Bologna/IT
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Abstract 3698

Background

Prognosis is poor for pts with GBM, as nearly all have recurrence after standard-of-care therapy. Nivo, a fully human IgG4 mAb inhibitor of the programmed death-1 receptor, is approved for the treatment of multiple cancers. Exploratory cohorts 1c and 1d of CheckMate 143 (NCT02017717) assessed the safety/tolerability of nivo in combination with RT ± TMZ in pts with newly diagnosed GBM.

Methods

In cohort 1c, pts received nivo 3 mg/kg Q2W + standard RT + concurrent TMZ (75 mg/m2 daily) followed by adjuvant TMZ (150-200 mg/m2; 5 days/28-day cycle for ≥ 6 cycles). In cohort 1d, pts received nivo 3 mg/kg Q2W + standard RT without TMZ. All pts continued to receive nivo until confirmed progression/unacceptable toxicity. Pts (n = 58) were initially assigned to 1c or 1d based on MGMT methylation status (1c, methylated or unmethylated; 1d, unmethylated). Following the initial evaluation, a second group of 55 pts with unmethylated MGMT were randomized 1:1 to 1c or 1d. Pooled safety data for all 113 pts are described here.

Results

Twelve pts with methylated and 43 pts with unmethylated MGMT were treated in 1c, and 58 pts with unmethylated MGMT were treated in 1d. Pts discontinued treatment in 1c (67% each arm) and 1d (83%) mostly due to radiographic progression (1c, 50% [methylated], 37% [unmethylated]; 1d, 64%), study drug toxicity (8%, 9%; 10%), or pt decision (8%, 14%; 0%). AEs (all cause) are summarized in Table. The most common (≥ 30% of pts in any arm) neurological AEs were headache (42%, 47%; 41%) and seizure (25%, 16%; 31%). No deaths due to study drug toxicity were reported.Table:

325O Summary of AEs (all cause)

Pts, n (%)1c: Nivolumab + RT + TMZ1d: Nivolumab + RT
Methylated MGMTUnmethylated MGMTUnmethylated MGMT
n = 12n = 43n = 58
AEs in ≥ 30% of pts in any arm
Fatigue9 (75)22 (51)25 (43)
Headache5 (42)20 (47)24 (41)
Nausea6 (50)13 (30)10 (17)
Seizure3 (25)7 (16)18 (31)
Constipation2 (17)14 (33)4 (7)
Alopecia4 (33)4 (9)7 (12)
Other neurological AEs in ≥ 15% of pts in any arm
Cognitive disorder2 (17)3 (7)6 (10)
Dizziness2 (17)4 (9)5 (9)
Visual field defect2 (17)2 (5)1 (2)
Immune-mediated AEs in > 2 pts in any arm
ALT increased3 (25)8 (19)7 (12)
Rash1 (8)7 (16)9 (16)
AST increased3 (25)7 (16)5 (9)
Diarrhea06 (14)8 (14)
Hypothyroidism1 (8)4 (9)6 (10)
Rash maculopapular3 (25)2 (5)4 (7)
Bilirubin increased1 (8)1 (2)3 (5)
Creatinine increased03 (7)2 (3)
Grade 3/4 AEs in > 2 pts in any arm
Lymphocytes decreased2 (17)5 (12)2 (3)
Lipase increased03 (7)4 (7)
ALT increased1 (8)2 (5)3 (5)
Seizure1 (8)3 (7)2 (3)
Tumor flare01 (2)4 (7)
Hyponatremia1 (8)03 (5)
Muscular weakness01 (2)3 (5)
Serious AEs in > 2 pts in any arm
Seizure3 (25)4 (9)7 (12)
Malignant neoplasm progression2 (17)2 (5)3 (5)
Pyrexia1 (8)3 (7)2 (3)
Tumor flare02 (5)4 (7)
Headache04 (9)1 (2)

Conclusions

Nivo with RT ± TMZ was well tolerated, with the frequency of neurological AEs consistent with that in other reports in this disease. These data support continued development of nivo + RT ± TMZ in newly diagnosed GBM in the ongoing CheckMate 498 (NCT02617589) and CheckMate 548 (NCT02667587) trials.

Clinical trial identification

CA209143; Revised Protocol 04d, dated September 15, 2016

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

G. Vlahovic: Ad Board: Bristol-Myers Squibb, Genentech, Merck. A. Omuro: Ad Board: Bristol-Myers Squibb, AstraZeneca, Merck, Alexion Therapeutics & Juno Therapeutics. Consulting: Stemline. D.A. Reardon: Honoraria, & Consulting: Abbvie, Amgen, Bristol-Myers Squibb, Genentech/Roche, Merck, Juno. Speakers Bureau: Genetech/Roche, Merck. Research funding: Celldex, Incyte, Inovio, Midatech. M. Lim: Honoraria & Consulting: Bristol-Myers Squibb, Merck, Agenus, Oncours. Research funding: Bristol-Myers Squibb, Agenus, Accuray. Patents/Royalty: John Hopkins. S. Sahebjam: Consulting: Bristol-Myers Squibb, Merck. Research funding: Bristol-Myers Squibb, Cortice, Merck. T. Cloughesy: Consulting: Bristol-Myers Squibb, Pfizer, Tocagen, Roche, Novocure, Nektar, VBL, Abbvie, Upshire Smith, Notable Labs, Oxigene, NewGen, Agios, Cortice, MedQia, ProNai, Wellcome, Merck, Insys, Human Longevity, Sunovion, Boston Biomedical, Alexion, Novogen. V. Potter, P. Paliwal, M. Carleton: Employee of Bristol-Myers Squibb. R. Zwirtes: Employment & stock holder with Bristol-Myers Squibb. J. Sampson: Royalties: Celldex. Shares/Equity: Istari Oncology. Consulting: Bristol-Myers Squibb. A.A. Brandes: Travel grant to ASCO by Roche. All other authors have declared no conflicts of interest.

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