1. CheckMate 204: Nivolumab + Ipilimumab in Pts With Advanced Melanoma and Asymptomatic, Untreated Brain Metastases
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Melanoma Brain Metastases: Background
Brain metastasis common in pts with melanoma and associated with poor prognosis (median OS: ~ 4-5 mos)[1]
Currently managed with local therapy, but this does not prolong survival and causes neurotoxicity
Surgery and/or stereotactic radiation therapy for oligometastatic disease
Whole-brain radiation therapy for miliary or leptomeningeal disease
Nivolumab + ipilimumab showed high response rates in a phase III study that excluded melanoma brain metastases[2]
Immunotherapy experience with brain metastases limited since these pts are typically excluded from clinical trials
Current report provides interim data from CheckMate 204 phase II study investigating nivolumab + ipilimumab in pts with melanoma and untreated melanoma brain metastases[3]
1. Davies MA, et al. Cancer. 2011;117: Larkin J, et al. N Engl J Med. 2015;373: Tawbi HA, et al. ASCO Abstract 9507.
Slide credit: clinicaloptions.com

3. CheckMate 204: Study Design
Multicenter phase II study
Melanoma pts with ≥ 1 unirradiated, measurable MBM ( cm); no leptomeningeal disease; prior SRT in ≤ 3 MBM; no neurologic symptoms; no steroids > 10 days, WBRT, or tx with checkpoint inhibitors; previous tx with BRAF/MEK inhibitors permitted (N = 109)
Induction
Maintenance
Nivolumab 1 mg/kg Q3W x 4
Ipilimumab 3 mg/kg Q3W x 4
Nivolumab 3 mg/kg Q2W
Until progression or unacceptable toxicity (maximum 24 mos)
Primary endpoint: intracranial CBR (CR + PR + SD for ≥ 6 mos)
Secondary endpoints: safety, OS, extracranial and global CBR
Safety and efficacy reported for 75 pts based on database lock in March 2017
Median follow-up: 9.2 mos
CBR, clinical benefit rate; MBM, melanoma brain metastases; PD, progressive disease; SD, stable disease; SRT, stereotactic radiation therapy; tx, treatment; WBRT, whole-brain radiation therapy.
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract 9507.

4. CheckMate 204: Baseline Characteristics
Nivolumab + Ipilimumab (N = 75)
Median age, range
59 (22-79)
Male, % 71
BRAF mutation, % 55
NRAS mutation, % 7
LDH > 2 x ULN, % 15
Prior systemic cancer therapy, %
Dabrafenib/trametinib
Vemurafenib 16 8 3
Prior SRT, % 9
Median target lesion diameter, mm (IQR)
9.0 ( )
> 3 target lesions, % 21
IQR, interquartile range; LDH, lactate dehydrogenase; SRT, stereotactic radiation therapy; ULN, upper limit of normal.
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract 9507.

5. CheckMate 204: Efficacy Outcomes
Nivolumab + Ipilimumab
(N = 75)
Intracranial
Extracranial
Global
CBR, % 60 52 59
ORR, % 55 49 53
Best overall response, % CR PR SD PD NE 21 33 5 24 16 7 43 3 27 48 17
Median PFS, mos (95% CI)
NR (7.5-NR)
NR (NR-NR)
NR (6.5-NR)
CBR, clinical benefit rate; NE, not evaluable; NR, not reached; PD, progressive disease; SD, stable disease.
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract 9507.

6. CheckMate 204: Time to and Duration of Intracranial Response
Outcome†
Nivolumab + Ipilimumab (n = 41‡)
Median time to response, mos (range)
2.8 ( )
Median duration of response, mos (range)
NR (NR-NR)
Ongoing response among responders, % 93
Pts
On treatment
Off treatment
First response (CR/PR)
Ongoing response
Progression
†Minimum follow-up of 6 mos from date of first dose.
‡n = 1 pt not included on plot, but undergoing
further evaluation.
NR, not reached. * * 8 16 24 32 40 48 56 64 72 80 88
Wks
*First tumor assessment at 6 ± 2 wks.
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract Reproduced with permission.

7. CheckMate 204: Safety Outcomes
AE, %
Nivolumab + Ipilimumab (N = 75)
All Grades
Grade 3/4
Any 96 52
Pts who discontinued due to AEs 31 25
Neurologic events
Headache
Brain edema
Intracranial hemorrhage
Peripheral motor neuropathy
Syncope 37 1 8 4
AE, adverse event; GI, gastrointestinal.
Median time to onset of grade 3/4 nervous system AEs: 33 days
Median time to resolution of grade 3/4 nervous system AEs: 4 days
Most frequent nonneurologic treatment-related AEs, any grade, include: skin (76%), general disorders (60%), GI (59%), and endocrine (39%)
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract 9507.

8. CheckMate 204: Investigator Conclusions
Nivolumab + ipilimumab may have clinically meaningful efficacy in pts with advanced melanoma and untreated brain metastases and offers new treatment option
Intracranial ORR: 55%, with 21% of pts achieving CR
Median PFS not reached; 6-mo PFS > 60%
Safety profile of nivolumab + ipilimumab consistent with earlier experience in pts without metastatic brain metastases
CheckMate 204 being expanded to include symptomatic pts and those requiring steroids
Slide credit: clinicaloptions.com
Tawbi HA, et al. ASCO Abstract 9507.

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