Present and future of immune checkpoint blockade: Monotherapy to adjuvant approaches

Table 1 Clinical study outcomes of ipilimumab (anti-cytotoxic T lymphocyte associated antigen-4) in solid tumors

Ref.	Phase	Cancer type	No. of patients	Dose (mg/kg)	Outcome
McDermott et al[73]	3	Melanoma	676	3	3-yr survival rate 25%
Hodi et al[74]	3	Melanoma	676	3	BORR: 10.9%
Robert et al[70]	3	Melanoma	676	3	BORR: 37.5%
Margolin et al[71]	2	Melanoma with brain metastasis	93	10	1Cohort A: 18% disease control 2Cohort B: 5% disease control
Di Giacomo et al[69]	N/A	Melanoma	27	10	2-yr survival rate 23.5%
Yang et al[78]	2	Pancreatic adenocarcinoma	27	3	No responders
O’Day et al[68]	2	Melanoma	155	10	BORR: 5.8%
Wolchok et al[67]	2	Melanoma	217	10	BORR: 11.1%
Yang et al[78]	2	RCC	40	3	PR: 12.5%
Phan et al[66]	1	Melanoma	14	3	OR: 21%

¹Cohort A includes neurologically asymptomatic patients not receiving corticosteroids;

²Cohort B includes symptomatic patients receiving corticosteroids. Dose indicates dose of Ipilimumab. Outcomes are best outcomes in each study, in patients receiving Ipilimumab only. BORR: Best overall response rate; RCC: Renal cell carcinoma; PR: Partial response; OR: Objective response; N/A: Not available.

Table 2 Clinical study outcomes of anti-programmed death-1 or anti-programmed death ligand-1 antibody in solid tumors

Ref.	Phase	Cancer type	No. of patients	Antibody type	Outcome
Hamid et al[75]	2	Melanoma	135	Lambrolizumab	RECIST: 1.1; RR: 38% (95%CI: 25-44)
Weber et al[85]	1	Melanoma	90	Nivolumab	RECIST: 1.1; RR: 25%
Brahmer et al[86]	1	Advanced cancers	207	Anti-PD-L1	OR: 6%-17%
Topalian et al[83]	1	Advanced cancers	296	Nivolumab	OR: 18%-36%

Dose indicates dose of anti-PD-1 antibody. RECIST: Response evaluation criteria in solid tumors; OR: Objective response, as defined by partial or complete tumor regression; RR: Response rate; PD-L1: Programmed death ligand-1.

Table 3 Ongoing clinical Trials in combination anti-programmed death-1 and anti-cytotoxic T lymphocyte associated antigen-4 Blockade

Identifier	Phase	Cancer type	Checkpoint antibodies	Status
NCT02060188	2	Microsatellite High (MSI-H) Colon Cancer	Nivolumab, ipilimumab	Recruiting
NCT01454102	1	NSCLC	Nivolumab, ipilimumab	Recruiting
NCT01472081	1	RCC	Nivolumab, ipilimumab	Recruiting
NCT01024231	1b	Melanoma	MDX-1106, ipilimumab	Active
NCT01928394	1/2	TNBC, GC, PC, SCLC, BC	Nivolumab, ipilimumab	Recruiting
NCT02017717	2b	GBM	Nivolumab, ipilimumab	Recruiting
NCT01927419	2	Melanoma	Nivolumab, ipilimumab	Active
NCT01844505	3	Melanoma	Nivolumab, ipilimumab	Active
NCT01592370	1	Hematologic malignancy	Nivolumab, ipilimumab	Recruiting
NCT01783938	2	Melanoma	Nivolumab1, ipilimumab	Recruiting

¹Nivolumab is sequentially dosed with Ipilimumab in this study, whereas in all other studies it is concurrently dosed. Identifier refers to Clinicaltrials.gov identifier. NSCLC: Non-small cell lung cancer; RCC: Renal cell carcinoma; TNBC: Triple negative breast cancer; GC: Gastric cancer; PC: Pancreatic cancer; SCLC: Small cell lung cancer; BC: Bladder cancer; GBM: Glioblastoma.

Table 4 Clinical study outcomes of combination chemotherapy and immune checkpoint blockade

Ref.	Phase	Cancer type	Treatment combination	Outcome
Robert et al[70]	3	Melanoma	Ipilimumab + dacarbazine	3-yr survival 20.8% (P < 0.001)
Lynch et al[94]	2	NSCLC	Ipilimumab + paclitaxel, carboplatin (phased)	irPFS HR: 0.72, P = 0.05
Reck et al[95]	2	SCLC	Ipilimumab + paclitaxel, carboplatin (phased)	irPFS HR: 0.64, P = 0.03
Hersh et al[90]	2	Melanoma	Ipilimumab + dacarbazine	ORR: 14.3% (95%CI: 4.8-30.3)

All outcomes are in combination therapy treatment arms. NSCLC: Non-small cell lung cancer; SCLC: Small cell lung cancer; irPFS: Immune-related progression free survival; HR: hazard ratio; ORR: Objective response rate.