Table 1.

Pivotal published clinical trials of immunotherapeutics in melanoma and NSCLC.

Immunotherapy	Trial	Phase	Intervention	Population	Recruitment Period	N	SOC	1st Comparator	2nd Comparator	Primary Endpoint	Results	p value
Melanoma
Ipilimumab
	Hodi et al.11	III	Ipilimumab v placebo	Previously treated metastatic melanoma (MM)	09/2004 – 08/2008	676	gp100	Ipilimumab + gp100	Ipilimumab 3 mg/kg	OS	Median OS:	p<0.001
											Ipilimumab + gp100: 10.0 mo
											Ipilimumab: 10.1 mo gp100: 6.4 mo
	Ribas et al.	II	Tremelimumab vs Dacarbazine (DTIC or Temozolomide	Previously untreated MM	03/2006 – 07/2007	655	Dacarbazine or Temozolomide	Tremelimumab	N/A	OS	Median OS:	p = 0.127
											Tremelimumab: 12.7 mo
											Chemotherapy: 10.8 mo
	Robert et al.30	III	Ipilimumab vs Dacarbazine (DTIC)	Previously untreated MM	08/2006 – 01/2008	502	Dacarbazine	Ipilimumab + Dacarbazine	N/A	OS	Median OS:	p<0.001
											Ipilimumab + DTIC: 11.2 mo
											DTIC: 9.1 mo
Pembrolizumab
	Ribas et al.31 (KEYNOTE-002)	II	Chemotherapy vs Pembrolizumab	MM after Ipilimumab or BRAF/MEK inhibitor	11/2012 – 11/2013	540	Investigator's choice chemotherapy	Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	OS (interim analysis PFS)	6 month PFS:	p<0.001
											Pembrolizumab (2 mg/kg) – 34%
											Pembrolizumab (10 mg/kg) – 38%
											Chemotherapy – 16%
	Robert et al.35 (KEYNOTE-006)	III	Ipilimumab vs Pembrolizumab	Previously treated MM (2nd line)	09/2013 – 03/2014	834	Ipilimumab 3 mg/kg	Pembrolizumab 10 mg/kg Q2W	Pembrolizumab 10 mg/kg Q3W	OS and PFS	6 month PFS:
											Pembrolizumab Q2W – 47.3%	p<0.001
											Pembrolizumab Q3W– 46.4%	p<0.001
											Ipilimumab – 26.5%
											1 y OS:
											Pembrolizumab Q2W – 74.1%	p<0.001
											Pembrolizumab Q3W– 68.4%	p = 0.004
											Ipilimumab – 58.2%
Nivolumab
	Weber et al.32 (CheckMate 037)	III	Nivolumab vs Dacarbazine (DTIC) or Carboplatin-Paclitaxel	Previously treated MM	12/2012 – 01/2014	405	Dacarbazine or Carboplatin/Paclitaxel	Nivolumab 3 mg/kg	N/A	ORR	ORR:
										OS	Nivolumab: 31.7%
											Chemotherapy: 10.6%
											OS not yet reported
	Robert et al.33 (CheckMate 066)	III	Nivolumab vs Dacarbazine (DTIC)	Previously untreated MM (BRAF WT)	01/2013 – 02/2014	518	Dacarbazine	Nivolumab 3 mg/kg	N/A	OS	1 y OS:	p<0.001
											Nivolumab: 72.9%
											Dacarbazine: 42.1%
Combination
	Postow et al.58	I	Ipilimumab vs Nivolumab + Ipilimumab	Previously untreated MM	09/2013 – 02/2014	175 (142 BRAF WT)	Ipilimumab 3 mg/kg	Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg Q3W; then Nivolumab 3 mg/kg Q2W	N/A	ORR in BRAF WT only	ORR:	p<0.001
	Hodi et al.59(CheckMate 069)										Ipilimumab + nivolumab: 61%
											Ipilimumab: 11%
											1 y OS:	p = 0.26
											Ipilimumab + nivolumab: 73%
											Ipilimumab: 65%
	Larkin et al.54	III	Ipilimumab vs Nivolumab + Ipilimumab OR Nivolumab alone	Previously untreated MM	07/2013 – 03/2014	945	Ipilimumab 3 mg/kg	Nivolumab 3 mg/kg Q2W	Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg Q3W	PFS and OS	Median PFS:	p<0.001
	Wolchok et al.60(CheckMate 067)										Ipilimumab: 2.9 mo
											Ipilimumab + nivolumab: 11.5 mo
											Nivolumab: 6.9 mo
											OS not yet reported
Talimogene Laherparepvec (T-VEC)
	Antbacka et al.53	III	T-VEC vs GM-CSF	Previously untreated MM	05/2009 – 07/2011	436	Intralesional T-VEC	Subcutaneous GM-CSF	N/A	DRR	DRR:	p<0.001
											T-VEC: 16.3%
											GM-CSF: 2.1%
NSCLC
Ipilimumab
	Lynch et al.23	II	Ipilimumab +/− Carboplatin-Paclitaxel	Previously untreated unresectable or metastatic NSCLC (mNSCLC)	02/2008 – 02/2009	204	Carboplatin-Paclitaxel	Concurrent regimen:	Phased regimen:	irPFS	Median irPFS:
								Ipilimumab 10 mg/kg + Carboplatin/Paclitaxel Q3W for 4 doses then 2 doses of chemotherapy	2 doses of Carboplatin/Paclitaxel Q3W then 4 doses of chemotherapy + Ipilimumab 10 mg/kg		Chemotherapy: 4.6 mo	p = 0.13
											Concurrent Rx: 5.5 mo	p = 0.05
											Phased Rx: 5.7 mo
											Median OS:
											Chemotherapy: 8.3 mo	p = 0.48
											Concurrent Rx: 9.7 mo	p = 0.23
											Phased Rx: 12.2 mo
Pembrolizumab
	Herbst et al.16 (KEYNOTE-010)	II/III	Pembrolizumab vs Docetaxel	Previously treated mNSCLC PD-L1 >1%	08/2013 – 02/2015	1034	Docetaxel	Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	PFS and OS	Median PFS
											Chemotherapy: 4.0 mo
											Pembrolizumab (2 mg/kg): 3.9 mo	p = 0.07
											Pembrolizumab (10 mg/kg): 4.0 mo	p = 0.004
											Median OS:
											Chemotherapy: 8.5 mo	p<0.001
											Pembrolizumab (2 mg/kg): 10.4 mo	p<0.001
											Pembrolizumab (10 mg/kg): 12.7 mo
	Reck et al.24 (KEYNOTE-024)	III	Chemotherapy vs Pembrolizumab	Previously untreated mNSCLC without activating mutation	08/2014	305	Platinum-based chemotherapy	Pembrolizumab 200 mg	N/A	PFS	Median PFS	p<0.001
											Chemotherapy: 6.0 mo
											Pembrolizumab: 10.3 mo
	Langer et al.56 (KEYNOTE-021)	II	Chemotherapy +/− pembrolizumab	Previously untreated mNSCLC	11/2014 – 01/2016	123	Carboplatin-Pemetrexed	Pembrolizumab 200 mg + Carboplatin-Pemetrexed	N/A	ORR	ORR:	p = 0.002
											Chemotherapy: 29%
											Chemotherapy + pembrolizumab: 55%
Nivolumab
	Brahmer et al.17 (CheckMate 017)	III	Nivolumab vs Docetaxel	Previously treated SqCC mNSCLC	10/2012 – 12/2013	272	Docetaxel	Nivolumab 3 mg/kg Q2W	N/A	OS	Median OS	p<0.001
											Docetaxel: 6.0 mo
											Nivolumab: 9.2mo
	Borghaei et al.18 (CheckMate 057)	III	Nivolumab vs Docetaxel	Previously treated Non-SqCC mNSCLC	11/2012 – 12/2013	582	Docetaxel	Nivolumab 3 mg/kg Q2W	N/A	OS	Median OS	p = 0.002
											Docetaxel: 9.4mo
											Nivolumab: 12.2mo
Atezolizumab
	Fehrenbacher et al.43 (POPLAR II)	II	Atezolizumab vs Docetaxel	Previously treated mNSCLC	08/2013 – 03/2014	287	Docetaxel	Atezolizumab 1200 mg	N/A	OS	Median OS	p = 0.04
											Docetaxel: 9.7 mo
											Atezolizumab: 12.6 mo

Notes: SOC = standard of care; MM = metastatic melanoma; mNSCLC = metastatic NSCLC; BRAF WT = BRAF wild-type; OS = overall survival; PFS = progression-free survival; ORR = overall response rate; SqCC = squamous cell carcinoma; non-SqCC = non squamous cell carcinoma