|
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
|
