KEYNOTE-006: Long-term Outcomes After Pembrolizumab for Advanced Melanoma 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.

Long-term Melanoma Outcomes After Pembrolizumab (KEYNOTE-006): Background Pembrolizumab, an anti–PD-1 mAb, is widely approved for treating advanced or metastatic melanoma KEYNOTE-006: pembrolizumab vs ipilimumab for unresectable stage III or IV melanoma[1] Pembrolizumab associated with superior PFS and OS, improved ORR, lower grade 3-5 toxicity[1] Current analysis evaluated long-term outcomes of KEYNOTE-006[2] All pts (median follow-up: 33.9 mos) Pts who completed protocol-specified 2-yr pembrolizumab treatment Slide credit: clinicaloptions.com 1. Robert C, et al. N Engl J Med. 2015;372:2521-2532. 2. Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Study Design International, randomized, open-label, active-controlled phase III study Stratified by ECOG PS (0 vs 1), line of therapy (1st vs 2nd), PD-L1 status (positive vs negative) Pembrolizumab 10 mg/kg IV Q2W (n = 279) Continued for 2 yrs or until PD or unacceptable toxicity Pts with unresectable stage III-IV melanoma with ECOG PS 0/1, ≤ 1 prior therapy (excluding anti–CTLA-4, PD-1, or PD-L1 tx), known BRAF-mutation status (N = 834) Pembrolizumab 10 mg/kg IV Q3W (n = 277) Ipilimumab 3 mg/kg IV Q3W x 4 doses (n = 278) DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; PD, progressive disease; PS, performance status; tx, treatment. Endpoints: primary: PFS, OS; secondary: ORR, DoR, safety Long-term analysis: pembrolizumab arms pooled for analyses; protocol-specified time on pembrolizumab: ≥ 21.6 mos Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Baseline Characteristics Pembrolizumab (n = 556) Ipilimumab (n = 278) Median age, yrs (range) 62 (18-89) 62 (18-88) Male, % 60 58 ECOG PS 0, % 69 68 Elevated LDH, % 32 33 BRAF V600–mutation positive, % 35 38 PD-L1 positive, % 80 81 M1c disease, % 66 64 1 prior therapy, % 34 ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status. Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Post-Study Therapy Pembrolizumab (n = 555) Ipilimumab (n = 256) Any antineoplastic therapy 44 54 Immunotherapy Anti–CTLA-4 Anti–PD-1 Anti–PD-L1 Anti–CTLA-4 + anti–PD-1 31 25 9* < 1 39 5 34† BRAF inhibitor ± MEK inhibitor 23 32 Chemotherapy 11 12 Other 4 *Pembrolizumab, n = 27; nivolumab, n = 22. †Pembrolizumab, n = 44; nivolumab, n = 42. Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Long-term Outcomes Pembrolizumab (n = 556) Ipilimumab (n = 278) HR (95% CI) Median PFS, mos (95% CI) 24 mos, % 33 mos, % 8.3 (6.5-11.2) 34 31 3.3 (2.9-4.1) 15 14 0.56 (0.47-0.67) Median OS, mos (95% CI) 32.3 (24.5-NR) 55 50 15.9 (13.3-22.0) 42 39 0.70 (0.58-0.86) ORR, % (95% CI) CR PR SD PD 42 (38-46) 13 (11-16) 29 (25-33) 21 (18-25) 29 (26-33) 16 (12-21) 3 (1-6) 14 (10-18) 25 (20-31) 39 (33-45) Median DoR, mos (range) NR (1.0+ to 33.8+) NR (1.1+ to 34.8+) DoR, duration of response; NR, not reached; PD, progressive disease; SD, stable disease. Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Outcomes After Completing Pembrolizumab 19% of pts receiving pembrolizumab completed protocol (n = 104) 98% (n = 102) alive after median follow-up 9.7 mos; 93% (n = 97) with ongoing responses Outcome Pts Who Completed Pembrolizumab (n = 104) Best overall response, % CR PR SD 23 65 12 Estimated PFS, % (95% CI) 91 (80-96)* Estimated PFS by best response, % (95% CI) 95 (69-99) 91 (74-97) 83 (48-96) SD, stable disease. *Median PFS: not reached. Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Exposure and Adverse Events AE Pembrolizumab (n = 555) Ipilimumab (n = 256) Median exposure, mos (range) 5.70 (0.03-29.60) 2.10 (0.03-3.00) Treatment-related AE, % Grade 3/4 Led to death Led to discontinuation 79 17 < 1 10 74 19 9 Immune-mediated AE, % 26 5 12 AE, adverse event. Most common immune-mediated AEs (all incidence ≤ 11%): hypothyroidism, hyperthyroidism, colitis, skin disorders, pneumonitis Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

KEYNOTE-006: Conclusions Superiority of pembrolizumab over ipilimumab confirmed in advanced melanoma with nearly 3-yr median follow-up Prolonged PFS, OS with pembrolizumab Favorable safety profile with pembrolizumab Favorable outcomes for pts who completed protocol-specified pembrolizumab treatment 91% PFS after median follow-up 9.7 mos Investigators concluded that data from this study further support pembrolizumab as standard of care for advanced melanoma Slide credit: clinicaloptions.com Robert C, et al. ASCO 2017. Abstract 9504.

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