category
target
drug
trial
phase
type of tumor
clinical efficacy
safety
Inhibitory pathways
LAG-3(CD223)
IMP321(Immuntep®)
I
Pancreatic cancer
No OR
1/17 rash, no severe AEs
I
BC
ORR 50%
No significant AEs from IMP321 alone
In combination with paclitaxel
II
BC
Ongoing
BMS-986016
I
Melanoma
ORR 16%, DCR 45%
Similar to nivolumab alone
In combination with nivolumab
LAG525
I/II
Solid malignancies
Ongoing
TIM-3
MBG453
I/II
Advanced malignancies
Ongoing
MEDI9447
I
Solid tumors
Ongoing
TIGIT
OMP-31M32
I
Solid tumors
Ongoing
VISTA
JNJ-61610588
I
Advanced tumors
Ongoing
CA-170
I
Solid tumors and lymphomas
This molecules also inhibits PD-L1/PD-L2
B7-H3 (CD276)
Enoblituzumab(MGA271)
I
Melanoma, prostate, solid tumors
SD > 12 weeks and tumor shrinkage(2–69%) in different tumor types
No dose-limiting toxicities, 6% with grade 3 AEs
Ongoing
I
Melanoma, HNSCC, NSCLC, urothelial cancer
In combination with pembrolizumab
MGD009
I
Melanoma, NSCLC, mesothelioma, urothelial cancer
DART protein that binds both CD3 and B7-H3
8H9
I
Neuroblastoma
17/21 patients were alive and free of disease after a median follow-up of 33 months
Self-limited myelosuppression
Antibody labeled with radioactive iodine
I
8H9-positive solid tumor involving peritoneum
Ongoing
I
Gliomas
Ongoing
I
CNS malignancies
Ongoing
KIR
Lirilumab
I/II
HNSCC
ORR 24%, DCR 52%
15% with grade 3–4 AEs
In combination with nivolumab and ipilimumab
IPH4102
I
CTCL
ORR 45%, 10/22 patients PR, 2 CR in skin and 5 CR in blood
6/22 with grade 3 or more AEs
Ongoing
A2aR
CPI-444
I
Solid tumors
DCR 42%
Most were mild, only 1/24 grade 3 AE (autoimmunehemolytic anemia)
Alone and in combination with atezolizumab
TGF- β
Trabedersen(AP12009)
I
Pancreatic cancer
Improved OS by 9.9–11.8 months, no improvement in PFS
Synthetic antisense oligonucleotide that hybridizes with RNA
M7824
I
Solid tumors
1/16 patients CR, 1 PR, 2 SD, 1 with 25% reduction of lesion size
No grade 4–5 AEs
Dual anti-PD-L1 antibody with TGF-β trap
Galusertinib(LY2157299)
II
Glioblastoma
No OS difference compared to lomustine alone
54% with grade 3–4 AEs
Alone or in conjunction with lomustine
I/II
NSLC, HCC
Ongoing
I
Pancreatic cancer
Ongoing
I
BC
Ongoing
PI3Kγ
IPI-549
I
Melanoma, NSCLC, HNSCC
12/15 patients with durable clinical benefit
No dose-limiting toxicities
Monotherapy or in conjunction with nivolumab
CD47
Hu5F9-G4
I
Solid tumors
2/16 patients SD for 8–16 months
Anemia 11/16 patients, hyperbilirubinemia 5/16, retinal toxicity 1/16
Ongoing
I/II
Relapsed or refractory NHL
In conjunction with rituximab Ongoing
TTI-621 (SIRPαFc)
I
Relapsed or refractory solid tumors and mycosis fungoides
Ongoing
CD73
MEDI9447
I
Solid tumors
Ongoing
Stimulatory pathways
OX40
9B12
I
Solid tumors
12/30 patients with tumor regression but not achieving PR, 6/30 SD
7/30 patients with grade 3 or more lymphopenia
MOXR 0916
I
Solid tumors
No dose-limiting toxicities
In conjunction with atezolizumab
PF-04518600 (PF-8600)
I
Melanoma, NSCLC
4/9 patients SD
No dose-limiting toxicities or grade 3–5 AEs
Ongoing
MEDI6383
I
Solid tumors
Ongoing
MEDI0562
I
Solid tumors
Ongoing
INCAGN01949
I
Solid tumors
Ongoing
GSK3174998
I
Solid tumors
Ongoing
GITR
TRX-518
I
Solid tumors
4/40 patients SD
No dose-limiting toxicities or grade 3–5 AEs
Ongoing
BMS-986156
I
Solid tumors
1/66 patients with grade 4 creatine phosphokinase elevation leading to discontinuation of treatment
Alone or in conjunction with nivolumab
AMG 228
I
CRC, HNSCC, urothelial carcinoma, and melanoma
0/30 patients had OR
27/30 had AEs consisting of hypophosphatemia, anemia, and fever
Terminated(business decision)
MEDI1873
I
Solid tumors
Ongoing
MEDI6469
I
CRC
Ongoing
MK-4166
I
Solid tumors
Ongoing
INCAGN01876
I/II
Solid tumors
Ongoing
I/II
Solid tumors
Alone or in conjunction with nivolumab or ipilimumab. Ongoing
GWN323
I
Solid tumors and lymphomas
Ongoing
ICOS
JTX-2011
I/II
Solid tumors
Not reported
No dose-limiting toxicities, 3/25 patients with grade 3 AEs
Alone or in conjunction with nivolumab. Ongoing
GSK3359609
I
Solid tumors
Ongoing
MEDI-570
I
NHL
Ongoing
4-1BB (CD137)
Utomilumab(PF-05082566)
I
Solid tumors
6/23 patients CR or PR
No dose-limiting toxicities, most were grade 1–2 AEs
In combination with pembrolizumab
I
NHL, NSCLC, RCC, HNSCC, melanoma
Alone or in conjunction with rituximab. Ongoing
I
Solid tumors
In conjunction with mogamulizumab
I
HNSCC, HCC, melanoma, RCC
In conjunction with OX40 Agonist PF-04518600
II
Solid tumors
In conjunction with avelumab
Urelumab
I/II
Solid tumors and NHL
3/60 patients with NHL achieved PR and 3/60 CR. 9/86 patients with combination therapy achieved PR
3% with elevated AST, 3% elevated ALT, 7% with serious AEs
In conjunction with nivolumab
I
Solid tumors and NHL
Completed
CD27-CD70
ARGX-110
I
T cell lymphoma
2/9 patients had a reduction of malignant clones > 90%, 1 radiological PR and 2 skin PR
Ongoing
I/II
CD70 positive malignancies
Ongoing
BMS-936561 (MDX-1203)
I
RCC and B cell lymphoma
SD 69%
2/16 patients had grade 3 hypersensitivity
Completed
Varilumab
I
Solid tumors
Not reported
1/33 patients developed a dose-limiting toxicity(hepatitis and kidney injury)
In conjunction with nivolumab
I
Gliomas
Ongoing
II
Melanoma
Ongoing
I/II
RCC
Terminated(portfolio re-prioritization)
I/II
Solid tumors
Terminated(portfolio re-prioritization)
CD40
CP-870893
I
Melanoma
Ongoing
I
Solid tumors
Ongoing
APX005M
I
NSCLC, melanoma, urothelial cancer, HNSCC
Ongoing
II
Esophageal and gastroesophageal tumors
Ongoing
I/II
Melanoma
In conjunction with pembrolizumab. Ongoing
I/II
Melanoma, NSCLC
In conjunction with nivolumab. Ongoing
ADC-1013
I
Solid Tumors
Completed
I
Solid Tumors
Ongoing
JNJ-64457107
I
Solid tumors
Ongoing
SEA-CD40
I
Solid tumors and lymphomas
Alone or in conjunction with pembrolizumab
RO7009789
I
Solid tumors
Ongoing
I
Pancreatic cancer
In conjunction with Nab-paclitaxel and gemcitabine. Ongoing
I
Solid Tumors
In conjunction with Emactuzumab. Ongoing
I
Solid Tumors
In conjunction with vanucizumab. Ongoing
Other pathways
IDO
BMS-986205
I
Solid tumors
3/42 patients with grade 3 autoimmune hepatitis
Indoximod
II
Melanoma
ORR 52%
No significant toxicities
Used in conjunction with ipilimumab, nivolumab, or pembrolizumab
I/II
Pancreatic cancer
ORR 37%
1/30 patients with colitis
Used in conjunction with gemcitabine and nab-paclitaxel
II
Prostate cancer
Median PFS increased from 4.1 to 10.3 months
No significant AEs
Ongoing
Epacadostat
I/II
Melanoma, NSCLC, CRC, HNSCC, glioblastoma, ovarian cancer, and HD
ORR 75% and DCR 100% in melanoma, ORR 11% and DCR 28% in ovarian cancer, ORR 4%, and DCR 24% in CRC
No dose-limiting toxicities
In conjunction with nivolumab
I/II
Solid tumors and NHL
37/244 patients with grade 3 or more AEs, 3% discontinued therapy due to AEs
In conjunction with pembrolizumab
I
Solid tumors
No OR, 7/25 patients achieved SD
1/52 patients developed grade 3 pneumonitis, 1/52 developed grade 3 fatigue
Completed
TLR
MEDI9197
I
Solid tumors
No severe AEs
In combination with durvalumab and radiation therapy
PG545 (pixatimod,pINN)
I
Solid tumors
DCR 38%
3/23 patients developed dose-limiting toxicities
Completed
Polyinosinic-polycytidylic acid polylysine carboxymethylcellulose(poly-ICLC)
I
HCC
PFS 66% at 6 months and 28% at 24 months, OS 69% after 1 year and 38% after 2 years
1/18 patients with severe AE with hepatic artery embolization
Completed
IL-2R
NKTR-214
I/II
Solid tumors
1 patient with melanoma had a mixed radiographic response, another melanoma patient had an unconfirmed CR
No dose-limiting toxicities
In conjunction with nivolumab. Ongoing
Arginase inhibitors
CB-1158
I
Solid tumors
No dose-limiting toxicities
Alone and in conjunction with nivolumab
Oncolytic peptides
LTX-315
I
Melanoma and BC
2/28 patients CR, 5/28 showed > 50% decrease in tumor size, 8/28 SD
Grade 1 and 2 EAs
Monotherapy or in conjunction with ipilimumab or pembrolizumab
IL-10
AM0010
I
Melanoma
DCR 45%
11/25 patients with grade 3–4 AEs
In conjunction with pembrolizumab

next generation of immune checkpoint therapy in cancer: new developments and challenges
Julian A. Marin-Acevedo et al.