cheakmate 067

1. CheckMate 067 6.5-Yr Follow-up: Long-term Safety
and Efficacy of Nivolumab and Ipilimumab for
First-line Treatment of Advanced Melanoma
Supported by educational grants from Bristol-Myers Squibb and Pfizer Inc.
CCO Independent Conference Highlights*
of the 2021 Virtual ASCO Annual Meeting, June 4-8, 2021
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.
Provided by Clinical Care Options, LLC

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Slide credit: clinicaloptions.com

3. CheckMate 067 6.5-Yr Follow-up: Background
 CheckMate 067 compared nivolumab plus ipilimumab with either
agent given alone in patients with previously untreated advanced
melanoma1
 After minimum follow-up of 60 mo, median OS with nivolumab plus
ipilimumab was not reached2
‒ Median OS with nivolumab was 36.9 mo and 19.9 mo with ipilimumab
‒ 5-yr OS rate: 52% nivolumab plus ipilimumab, 44% nivolumab,
26% ipilimumab
 Current analysis reports efficacy and safety at 6.5-yr follow-up from
CheckMate 0673
1. Larkin. NEJM. 2015;373:23. 2. Larkin. NEJM. 2019;381:1535.3. Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com

4. CheckMate 067 6.5-Yr Follow-up: Study Design
 Multicenter, randomized, double-blind phase III trial
 Coprimary endpoints: PFS, OS
 Secondary endpoints: ORR, tumor PD-L1 expression and efficacy, safety
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com
Patients with previously
untreated unresectable
stage III/IV melanoma and
ECOG PS 0-1
(N = 945)
Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for
4 doses, then Nivo 3 mg/kg Q2W
(n = 314)
Nivo 3 mg/kg Q2W + Placebo
(n = 316)
Until disease
progression or
unacceptable toxicity
Stratified by PD-L1 expression (<5% vs ≥5%),
BRAF mutation status, and AJCC M stage
Ipi 3 mg/kg Q3W for 4 doses + Placebo
(n = 315)

5. CheckMate 067 6.5-Yr Follow-up: PFS
Wolchok. ASCO 2021. Abstr 9506. Reproduced with permission. Slide credit: clinicaloptions.com
Nivo + Ipi
(n = 314)
Nivo
(n = 316)
Ipi
(n = 315)
Median PFS, mo (95% CI) 11.5 (8.7-19.3) 6.9 (5.1-10.2) 2.9 (2.8-3.2)
HR (95% CI) vs Ipi 0.42 (0.35-0.51) 0.53 (0.44-0.64) --
HR (95% CI) vs Nivo* 0.79 (0.65-0.97) -- --
*Descriptive analysis. The study was not powered to compare Nivo/Ipi vs Nivo.
PFS(%)
100
80
60
0
40
20
0
Mo
3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84
Nivo + Ipi
Nivo
Ipi
X
X
X
X
X
X
X
X
X
XX X
X
X
X
XX X
X X
X X
X X
X
X X
X X
X X
X X
X X X
X X
X X
X X
X X
X X
X X X
X X
X X
X X
X
36% 36% 34%
29% 29% 29%
7% 7% 7%

6. CheckMate 067 6.5-Yr Follow-up: OS
Wolchok. ASCO 2021. Abstr 9506. Reproduced with permission. Slide credit: clinicaloptions.com
Nivo + Ipi
(n = 314)
Nivo
(n = 316)
Ipi
(n = 315)
Median OS, mo (95% CI) 72.1 (38.2-NR) 36.9 (28.2-58.7) 19.9 (16.8-24.6)
HR (95% CI) vs Ipi 0.52 (0.43-0.64) 0.63 (0.52-0.76) --
HR (95% CI) vs Nivo* 0.84 (0.67-1.04) -- --
*Descriptive analysis. The study was not powered to compare Nivo/Ipi vs Nivo.
OS(%)
100
80
60
0
40
20
0
Mo
3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84
Nivo + Ipi
Nivo
Ipi
X
X
X
X
X
X
X
X X X
X
52% 50% 49%
44% 43% 42%
26% 23% 23%
87
X X X X
X
X
X
X
X
X
X X
X X
X X

7. CheckMate 067 6.5-Yr Follow-up:
Post Hoc Analysis of Melanoma-Specific Survival
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com
 Events defined as death due to melanoma; deaths due to other causes were censored.
Nivo + Ipi
(n = 314)
Nivo
(n = 316)
Ipi
(n = 315)
Median OS, mo (95% CI) NR (71.9-NR) 58.7 (35.9-NR) 21.9 (18.1-27.4)
HR (95% CI) vs Ipi 0.48 (0.39-0.60) 0.59 (0.48-0.73) --
HR (95% CI) vs Nivo* 0.81 (0.64-1.03) -- --
Melanoma-Specific
Survival
(%)
*Descriptive analysis. The study was not powered to compare Nivo/Ipi vs Nivo.
100
80
60
0
40
20
0
Mo
3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84
Nivo + Ipi
Nivo
Ipi
X
57% 56%
50% 48%
30% 27%
87
X
XX
X
X
X
X
X X
X X
X X X
X X
X
X
X
X
X X
X X
X X
X
X
X
X
X
X
X X
X
X
X X

8. CheckMate 067 6.5-Yr Follow-up: Response
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com
Response At 6.5 Yrs
Nivo + Ipi
(n = 314)
Nivo
(n = 316)
Ipi
(n = 315)
ORR, % (95% CI) 58 (53-64) 45 (39-51) 19 (15-24)
Best overall response, %
 CR
 PR
 SD
 PD
 Unknown
23
36
12
24
6
19
26
9
38
8
6
13
22
50
9
Median duration of response, mo
(95% CI)
NR (61.9-NR) NR (45.7-NR) 19.2 (8.8-47.4)

9. CheckMate 067 6.5-Yr Follow-up:
Overall Survival Outcomes by BRAF Mutation Status
Wolchok. ASCO 2021. Abstr 9506. Reproduced with permission. Slide credit: clinicaloptions.com
Nivo + Ipi
(n = 103)
Nivo
(n = 98)
Ipi
(n = 100)
Median (95% CI), mo NR (50.7-NR) 45.5 (26.4-NR) 24.6 (17.9-31.0)
HR (95% CI) vs Ipi 0.43 (0.30-0.60) 0.63 (0.44-0.90) --
HR (95% CI) vs Nivo 0.68 (0.46-1.0) -- --
Nivo + Ipi
Nivo
Ipi
X
BRAF mutant
100
80
0
40
20
0 3 6 9 12151821242730333639424548515457606366697275 78818487
60
OS
(%)
Mo
60%
46%
30%
43%
57%
25%
Nivo + Ipi
(n = 211)
Nivo
(n = 218)
Ipi
(n = 215)
Median (95% CI), mo 39.1 (27.5-NR) 34.4 (24.1-59.2) 18.5 (14.1-22.7)
HR (95% CI) vs Ipi 0.58 (0.45-0.74) 0.63 (0.50-0.80) --
HR (95% CI) vs Nivo 0.92 (0.71-1.18) -- --
BRAF wild-type
Nivo + Ipi
Nivo
Ipi
X
100
80
0
40
20
0 3 6 9 12151821242730333639424548515457606366697275 78818487
60
OS
(%) Mo
48%
43%
25% 22%
42%
46%
X
X
X
X
X
X
XX X X X
XX
X X XX
XX
X
X
X
X
X
X
X
XX
X
X
X
XX
X

10. CheckMate 067 6.5-Yr Follow-up:
Survival Outcomes by BRAF Mutation Status
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com
Outcome
BRAF Mutant BRAF Wild Type
Nivo + Ipi
(n = 103)
Nivo
(n = 98)
Ipi
(n = 100)
Nivo + Ipi
(n = 211)
Nivo
(n = 218)
Ipi
(n = 215)
Median PFS,
mo (95% CI)
16.8 (8.3-32.0) 5.6 (2.8-9.5) 3.4 (2.8-5.2) 11.2 (7.0-18.1) 8.2 (5.1-19.6) 2.8 (2.8-3.1)
HR (95% CI) vs
IPI
0.44 (0.31-0.62) 0.71 (0.41-0.98) 0.41 (033-0.52) 0.47 (0.38-0.59)
Liver Metastases No Liver Metastases
Outcome
Nivo + Ipi
(n = 93)
Nivo
(n = 90)
Ipi
(n = 92)
Nivo + Ipi
(n = 221)
Nivo
(n = 226)
Ipi
(n = 223)
Median OS,
mo (95% CI)
28.2 (15.2-71.9) 18.2 (8.1-32.3) 13.1 (9.6-18.4) NR (50.7-NR) 52.7 (36.0-NR) 23.5 (18.6-29.4)
HR (95% CI) vs
IPI
0.66 (0.46-0.93) 0.81 (0.58-1.14) 0.47 (0.37-0.60) 0.56 (0.44-0.71)

11. CheckMate 067 6.5-Yr Follow-up: Subsequent Therapy
Subsequent Therapy, n (%)
Nivo + Ipi
(n = 314)
Nivo
(n = 316)
Ipi
(n = 315)
Any subsequent therapy 146 (46.5) 188 (59.5) 238 (75.6)
 Subsequent systemic therapy 112 (36) 154 (49) 209 (66)
 Subsequent immunotherapy 59 (19) 107 (34) 151 (48)
– Anti–PD-1 agents 43 (14) 52 (16) 146 (46)
– Anti–CTLA-4 agents 23 (7) 92 (29) 19 (6)
 BRAF inhibitor 43 (14) 61 (19) 72 (23)
 MEK/NRAS inhibitor 34 (11) 44 (14) 42 (13)
Subsequent radiotherapy 71 (23) 96 (30) 128 (41)
Subsequent surgery 69 (22) 75 (24) 97 (31)
Median time from randomization to
subsequent systemic therapy, mo (95% CI)
NR (59.6-NR) 25.2 (16.0-43.2) 8.0 (6.5-8.7)

12. CheckMate 067 6.5-Yr Follow-up:
Patients Alive and Treatment-free
Wolchok. ASCO 2021. Abstr 9506. Reproduce with permission. Slide credit: clinicaloptions.com
On study therapy Received subsequent systemic therapy Treatment-free (off study treatment and
never received subsequent systemic therapy)
Nivo + Ipi (n = 145) Nivo (n = 122) Ipi (n = 63)
77%
n = 112
18%
n = 26
5%
n = 7
69%
n = 84
25%
n = 30
7%
n = 8
43%
n = 27
57%
n = 36
Median follow-up 80.8
(range 74.0-86.3)
Median follow-up 80.8
(range 76.4-85.3)
Median follow-up 80.8
(range 77.0-85.6)

13. CheckMate 067 6.5-Yr Follow-up: Safety
 No new safety issues emerged in extended follow-up
 No further treatment-related deaths after 36-mo analysis
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com
Treatment-related AE
Nivo + Ipi
(n = 313)
Nivo
(n = 313)
Ipi
(n = 311)
Any
Grade
Grade
3/4
Any
Grade
Grade
3/4
Any
Grade
Grade
3/4
TRAE, % 96 59 87 24 86 28
TRAE leading to d/c, % 42 31 14 8 15 13
Treatment-related death, n (%) 2 (1) 1 (<1) 1 (<1)

14. CheckMate 067 6.5-Yr Follow-up: Conclusions
 After 6.5 yr of follow-up, a median OS of 72.1 mo was observed with nivolumab +
ipilimumab in patients with advanced melanoma
‒ Median OS with nivolumab alone was 36.9 mo and 19.9 mo with ipilimumab alone
‒ Durable clinical benefit was seen in all subgroups, including in patients with liver
metastases at baseline and BRAF mutant tumors
‒ Fewer than one half of patients (47%) receiving nivolumab + ipilimumab received
subsequent therapy and the median time to subsequent therapy has not yet been
reached vs 25.2 mo for nivolumab and 8.0 mo with ipilimumab
‒ 77% of patients receiving nivolumab + ipilimumab and 69% of patients receiving nivolumab
alone remained alive and off treatment at 6.5 yr
‒ No new safety issues or additional treatment-related deaths emerged
Wolchok. ASCO 2021. Abstr 9506. Slide credit: clinicaloptions.com

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