Table 2 Clinical trials for checkpoint inhibitors alone and compared to standard care of treatment

Ipilimumab (CTLA-4)

Advanced uveal melanoma

II

Ipilimumap

SD 47%

6.8 (2.8)

Colitis, diarrhea, elevated liver enzymes

[176]

After complete resection of advanced melanoma

III

Ipilimumab or placebo after complete resection

NM

(26.7 vs 17.1)

Diarrhea, colitis,rash, pruritus, hypo-physitis, elevated liver enzymes

[170]

Advanced melanoma

II

Ipilimumap

CR 0% PR 10%

SD 10%

PD 65%

8.7 (2.7)

Elevated liver enzymes

[205]

Relapse of malignancy after allogeneic hematopoietic stemcell transplan-tation

I

Ipilimumab

ORR 6.9%

CR 6.9%

PR 3.4%

24.7

Arthritis, pneumonitis

[175]

Relapsed and refractory B-cell NHL

I

Ipilimumap

NM

NM

Diarrhea, fatigue,

[206]

Treme-limumap (CTLA-4)

Advanced melanoma

III

Tremeli-mumab vs. standard-of-care chemotherapy

NM

12.6 vs 10.7 (at 6 MO 20.3%vs 18.1%)

Diarrhea, colitis,

pruritus, rash

[183]

Advanced melanoma

I

Anti-CD40 + Tremeli-mumab

NM

26.1 (2.5)

Diarrhea, colitis, pruritus, rash

[212]

Advanced gastric and esophageal adeno-carcinoma

II

Tremeli-mumap

PR 5.6%

SD 22%

4.8 (2.8)

Diarrhea, atrial fibrillation, increased liver enzymes

[177]

Advanced (metastatic) colorectal carcinoma

II

Tremeli-mumap

PR 2.2% PD 95.6%

At 1a 4.8 vs 10.7% (at 6 MO 2.3 vs 2.1%)

Diarrhea, fatigue, colitis

[185]

Advanced NSCLC

II

Tremeli-mumap vs. best supportive care

PR 4.8%

SD 16.6%

20.9% (34%) at 3 MO

Diarrhea, colitis

[213]

HHC and chronic hepatitis C

II

Tremeli-mumap

SD 58.8%

PR 17.6%

8.2 (6.5)

Skin rash, diarrhea, syncope, diverticulitis, depression

[179]

Advanced malignant mesothelioma

II

Tremeli-mumap

PR 3%

SD 38%

11.3

Gastrointes-tinal events, dermatologi-cal events, fever

[214]

Nivolumab (PD-1)

Advanced refractory squamous NSCLC

II

Nivolumab 3 mg/kg every 2 weeks until progression

PR 14.5%

SD 26%

PD 44%

8.2 (1.9); 1a 40.1%

Fatigue, diarrhea, rash pruritus

[196]

Untreated melanoma (BRAF wild type vs mutated)

I

Nivolumab + Ipilimumab vs Ipilimumab + placebo

WT [BRAF+]

ORR 61% vs 11% [3% vs 1%] CR 16% vs 0%

[5% vs 0%] PR 28% vs 4%

[7% vs 1%] SD 9% vs 13% [5% vs 7%]

NM

Diarrhea rash. fatigue pruritus, elevated liver enzymes

[187]

Untreated melanoma without BRAF mutation

III

Nivolumab vs Dacarbazine

ORR 40,0% vs 13,9%

72.9% vs 42.1% at 1a (5.1 vs 2.2)

Fatigue, pruritus, nausea, diarrhea

[186]

Advanced Squamous-Cell NSCLC

III

Nivolumab vs Docetaxel

ORR 20 vs 9%

CR 1 vs 0%

PR 26 vs 12%

SD 39 vs 47%

PD 56% vs 48%

9.2 vs 6.0 (3.5 vs 2.8)

Fatigue, leukopenia

[191]

Advanced non-Squamous-Cell NSCLC

III

Nivolumab vs Docetaxel

ORR 19% vs 12% CR 4 vs 1%

PR 52% vs 35%

SD 12;7% vs 21% PD 22.2% vs 14.6%

12.2 vs 9.4 (2.3 vs 4.2)

Fatigue, nausea, diarrhea

[192]

Relapsed or refractory Hodgkin 's lymphoma

I

Nivolumab

CR 17%

PR 70%

SD 13%

NM

Leukopenia, stomatitis increased lipase levels, pancreatitis

[206]

Pretreated advanced NSCLC (s and ns)

I

Nivolumab

ORR 17.1% (16.7% s vs 17.6% ns)

9.9

Rash, Colitis

[190]

Untreated melanoma

III

Nivolumab vs Nivolumab + Ipilimumab vs Ipilimumab

ORR 14.6% vs 19.2% vs 6.3%

CR 8.9% vs 11.5% vs 2.2%

PR 34.8% vs 46.2% vs 16.8% SD 10.8% vs 13.1% vs 21.9% PD 37.7% vs 22.6% vs 48.9%

11.5 vs 2.9 vs 6.9

Diarrhea, fatigue, pruritus, rash

[188]

Platinum resistant ovarian cancer

II

Ipilimumab

CR 10% PR 5%

SD 30%

PD 50%

20 (3.5)

Lympho-cytopenia, anemia

[215]

Advanced melanoma after anti CTLA-4 treatment

III

Nivolumab vs investigators choice of chemo

ORR 31.7% vs 10.6%

CR 3.3% vs 0% PR 28.3% vs 10.6%

SD 23.3% vs 34%

PD 35% vs 31.9%

(4.7 vs 4.2)

Anemia, fatigue, vomitting

[189]

Advanced renal cell carcinoma

III

Nivolumab vs Everolimus

ORR 25% vs 5% CR 1% vs <1%

25.0 vs 19.6 (4.6 vs 4.4)

Fatigue, diarrhea, rash

[216]

Pembroli-zumab (PD-1)

Advanced NSCLC

I

Pembroli-zumab

ORR 19.4%

12.0 (3.7)

Fatigue, rash, diarrhea

[217]

Advanced triple negative breast cancer

Ib

Pembroli-zumab

ORR 18.5% CR 3.7%; PR 14.8% SD 25.9% PD 48.1%

NM

Anemia, headache,

[218]

Previously treated advanced non-small-cell lung cancer

II/III

Pembroli-zumab vs Docetaxel

NM

10.4 vs 12.7 vs 8.5 (3.9 vs 4.0 vs 4.0)

Anemia, headache,

[193]

Advanced melanoma

I

Pembroli-zumab

ORR 38.6% vs 28.6%

23 (4)

Anemia, headache,

[194]

Progressive metastatic carcinoma with or without mismatch repair-deficiency

II

Pembroli-zumab

ORR 40% vs 78% for mismatch repair-deficienct CRC and 0% vs 11% mismatch repair-proficient colorectal cancer

NM

Lympho-penia, anemia, diarrhea, bowel obstruction, elevated liver enzymes

[195]

Advanced melanoma

III

Pembrolizumab vs Ipilimumab

ORR 89.4% vs 96.7% vs 87.9%

At 1a 74.1% vs 68.4% (at 6 MO 47.3%vs 46.4% vs 26.5%)

Lympho-penia, anemia, diarrhea, bowel obstruction, elevated liver enzymes

[219]

Atezoli-zumab (PD-L1)

Previously treated metastatic uorthelial carcinoma

II

Atezoli-zumab

ORR 15% CR 5% PR 10% SD 19% PD 51%

NM

Fatigue, decreased appetite, dyspnoea, anemia, colitis

[202]

Previously treated NSCLC

II

Atezo-lizumab vs Docetaxel

NM

12.6 vs 9.7

Diarrhea, asthenia, neutropenia

[201]