Table 3 Clinical trials for checkpoint inhibitors in combination with standard care of treatment

Ipilimumab (CTLA-4)

Advanced melanoma

III

Ipilimumab or Ipilimumab + glycoprotein 100 or glycoprotein 100 only

NM

10 vs 10.1 vs 6.4 (2.76 vs 2.86 vs 2.76)

Diarrhea, nausea, constipation, vomiting, abdominal pain

[171]

Advanced melanoma

Retrospective

Ipilimumab or maintenance + median 30 Gy

NM

9 vs 39

NM

[172]

Advanced melanoma

Retrospective

Ipilimumab vs Ipilimumab + radiotherapy

NM

10.2 vs 19.6

Rash, colitis, GI, fatigue

[173]

Advanced melanoma

I

Ipilimumab plus radiotherapy

NM

10.7 (3.8)

Anemia, diarrhea, colitis

[220]

Metastatic melanoma

II

Ipilimumab + sargramostim vs Ipilimumab alone

NM

17.5 vs 12.7 (3.1 vs 3.1)

Diarrhea, rash, colitis, elevated liver enzymes

[174]

Metastatic NSCLC

I

Ipilimumab + Paclitaxel vs Ipilimumab + Carboplatin

NM

NM

Adrenal insuffiency, enterocolitis

[221]

Advanced, bone metastasis, castration-resistant prostate cancer

III

Ipilimumab or placebo after 8 GY

NM

11.2 vs 10.2 (4.0 vs 3.1; at 6 MO 30.7% vs 18.1%)

Diarrhea, colitis

[222]

Tremel-imumap (CTLA-4)

Prostate cancer (PSA-recurrent)

I

Tremeli-mumab + Bicalutamide

NM

NM

Colitis

[208]

Advanced breast cancer

I

Tremeli-mumab + Exemestane

SD 42%

NM

Diarrhea, rash

[207]

Metastatic pancreatic cancer

I

Tremeli-mumab + Gemcitabine

PR 10.5%

7.4

Asthenia, nausea, diarrhea

[223]

Advanced melanoma (or solid tumors)

I

Tremeli-mumab + PF-3512676 (CPG 7909) = Toll like receptor 9 inhibitor

NM

19

Diarrhea, hypophy-sitis, colitis, nausea, vomiting, pruritus, rash, neutropenia, rectal Bleeding

[224]

Advanced melanoma

II

Trimilimumab + high dose INFalpha (HDI)

ORR 24% CR 11% PR 14% SD 38%

21 (6.4)

Diarrhea, colitis, elevated liver enzymes, rash, fatigue, anxiety/depression

[184]

Metastatic renal cell carcinoma

I

Tremeli-mumab + sunitinib

PR 42.8%; SD 9.5%

2.8–18.2MO

Fatigue, mucositis, dypnea

[225]

Nivolumab (PD-1)

Resected advanced melanoma

II

Adjuvant Nivolumab + multi-peptide vaccine (gp100, MART-1 & NY-ESO-1 with Montanide ISA 51 VG)

NM

At 1a 87%

At 2a 82%

Colitis, enteritis, rash, hypokalemia

[226]

Pidilizumab (PD-1)

Relapsed follicular lymphoma

II

Pidilizumab + Rituximab

ORR 66% CR 52% PR 14%

NM

No grade 3 or higher irAE

[199]

DLBCL

II

Pidilizumab after autologous hematopoietic stem- cell transplan-tation

ORR 51% CR 34% PR 17% SD 37% PD 11%

At 16 MO 0.85% (at 16 MO 0,72%)

Thrombo-cytopenia, anemia, pyrexia, renal failure,

[200]

Atezoli-zumab (PD-L1)

Microsatellite stable metastatic colorectal cancer

Ib

Combination of cobimetinib and ateolizumab

ORR 17% and 20% in KRAS-mutant tumors

At 6 MO 72%

NM

[203]