Table 3 Clinical studies that supported approval of the combination

Advanced melanoma

Phase 1

NCT01024231

≥24 weeks

ORR, 53%

Grade 3-4 AEs, 53%

Wolchok et al 2013

Previously untreated advanced melanoma

Phase 1

NCT01927419

≥11 months

In patients with BRAF-WT tumors

ORR 61%

Median PFS, not reached

HR for disease progression or death, 0.40

Grade 3-4 AEs, 54%

Postow et al 2015

Previously untreated advanced melanoma

Phase 3

NCT01844505

> 12 months

Median PFS, 11.5 months

HR for death or disease progression, 0.42

Investigator assessed ORR, 57%

Grade 3-4 AEs, 55%

Larkin et al 2015

Previously untreated advanced melanoma

Phase 3

NCT01844505

≥ 36 months

Median OS, not reached

3-year OS rate, 58%

HR for death, 0.55

Grade 3-4 AEs, 59%

Wolchok et al 2017

Previously untreated advanced melanoma

Phase 3

NCT01844505

≥ 48 months

Median OS, not reached

4-year OS rate, 54%

ORR, 58%

HR for death, 0.54

HR for progression-free survival, 0.42

Grade 3-4 AEs, 59%

Hodi et al 2018

Advanced melanoma patients with at least one brain metastasis

Phase 2

NCT02320058

≥ 6 months

Rate of intracranial clinical benefit, 57%; Rate of extracranial clinical benefit, 56%

9-month PFS (global) rate, 57%; 9-month OS rate, 83

12-month OS rate, 82%

Grade 3-4 AEs, 55%

Tawbi et al 2018

Advanced melanoma

Phase 2

NCT01783938

≥ 15 months

ORR, 56%

Median OS, not reached

1-year OS rate, 76%

Grade 3-5 AEs, 50%

Weber et al 2018

Previously untreated advanced clear cell renal cell carcinoma

Phase 3

NCT02231749

> 17 months

ORR, 42%

Median OS, not reached

HR for death, 0.63

Median PFS, 11.6 months

HR for disease progression, 0.82

Motzer et al 2018

Previously treated, MMR/MSI-H positive advanced colorectal cancer

Phase 2

NCT02060188

> 9 months

ORR, 55%

Median PFS, not reached

12-month PFS rate, 71%

Median OS, not reached

12-month OS rate, 85%

Grade 3-4 AEs, 32%

Overman et al 2018