Table 1 Summary of ongoing phase 1/2 clinical trials utilizing immune checkpoint therapy

Inhibitory pathways

LAG-3 (CD223)

IMP321 (Immuntep®)

NCT00732082

I

Pancreatic cancer

No OR

1/17 rash, no severe AEs

In combination with gemcitabine

NCT00349934

I

BC

ORR 50%

No significant AEs from IMP321 alone

In combination with paclitaxel

NCT02614833

II

BC

–

–

Ongoing

BMS-986016

NCT01968109

I

Melanoma

ORR 16%, DCR 45%

Similar to nivolumab alone

In combination with nivolumab

LAG525

NCT02460224

I/II

Solid malignancies

–

–

Ongoing

TIM-3

MBG453

NCT02608268

I/II

Advanced malignancies

–

–

Ongoing

MEDI9447

NCT02503774

I

Solid tumors

–

–

Ongoing

TIGIT

OMP-31M32

NCT03119428

I

Solid tumors

–

–

Ongoing

VISTA

JNJ-61610588

NCT02671955

I

Advanced tumors

–

–

Ongoing

CA-170

NCT02671955

I

Solid tumors and lymphomas

–

–

This molecules also inhibits PD-L1/PD-L2

B7-H3 (CD276)

Enoblituzumab (MGA271)

NCT01391143

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

NCT02475213

I

Melanoma, HNSCC, NSCLC, urothelial cancer

–

–

In combination with pembrolizumab

MGD009

NCT02628535

I

Melanoma, NSCLC, mesothelioma, urothelial cancer

–

–

DART protein that binds both CD3 and B7-H3

8H9

NCT00089245

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

NCT01099644

I

8H9-positive solid tumor involving peritoneum

–

–

Ongoing

NCT01502917

I

Gliomas

–

–

Ongoing

NCT00089245

I

CNS malignancies

–

–

Ongoing

KIR

Lirilumab

NCT01714739

I/II

HNSCC

ORR 24%, DCR 52%

15% with grade 3–4 AEs

In combination with nivolumab and ipilimumab

IPH4102

NCT02593045

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

NCT02655822

I

Solid tumors

DCR 42%

Most were mild, only 1/24 grade 3 AE (autoimmune hemolytic anemia)

Alone and in combination with atezolizumab

TGF- β

Trabedersen (AP12009)

NCT00844064

I

Pancreatic cancer

Improved OS by 9.9–11.8 months, no improvement in PFS

-

Synthetic antisense oligonucleotide that hybridizes with RNA

M7824

NCT02517398

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)

NCT01582269

II

Glioblastoma

No OS difference compared to lomustine alone

54% with grade 3–4 AEs

Alone or in conjunction with lomustine

NCT02423343

I/II

NSLC, HCC

–

–

Ongoing

NCT02734160

I

Pancreatic cancer

–

–

Ongoing

NCT02672475

I

BC

–

–

Ongoing

PI3Kγ

IPI-549

NCT02637531

I

Melanoma, NSCLC, HNSCC

12/15 patients with durable clinical benefit

No dose-limiting toxicities

Monotherapy or in conjunction with nivolumab

CD47

Hu5F9-G4

NCT02216409

I

Solid tumors

2/16 patients SD for 8–16 months

Anemia 11/16 patients, hyperbilirubinemia 5/16, retinal toxicity 1/16

Ongoing

NCT02953509

I/II

Relapsed or refractory NHL

–

–

In conjunction with rituximab Ongoing

TTI-621 (SIRPαFc)

NCT02890368

I

Relapsed or refractory solid tumors and mycosis fungoides

–

–

Ongoing

CD73

MEDI9447

NCT02503774

I

Solid tumors

–

–

Ongoing

Stimulatory pathways

OX40

9B12

NCT01644968

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

Completed

MOXR 0916

NCT02410512

I

Solid tumors

–

No dose-limiting toxicities

In conjunction with atezolizumab

PF-04518600 (PF-8600)

NCT02315066

I

Melanoma, NSCLC

4/9 patients SD

No dose-limiting toxicities or grade 3–5 AEs

Ongoing

MEDI6383

NCT02221960

I

Solid tumors

–

–

Ongoing

MEDI0562

NCT02705482

I

Solid tumors

–

–

Ongoing

INCAGN01949

NCT02923349

I

Solid tumors

–

–

Ongoing

GSK3174998

NCT02528357

I

Solid tumors

–

–

Ongoing

GITR

TRX-518

NCT01239134

I

Solid tumors

4/40 patients SD

No dose-limiting toxicities or grade 3–5 AEs

Ongoing

BMS-986156

NCT02598960

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

NCT02437916

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

NCT02583165

I

Solid tumors

–

–

Ongoing

MEDI6469

NCT02559024

I

CRC

–

–

Ongoing

MK-4166

NCT02132754

I

Solid tumors

–

–

Ongoing

INCAGN01876

NCT02697591

I/II

Solid tumors

–

–

Ongoing

NCT03126110

I/II

Solid tumors

–

–

Alone or in conjunction with nivolumab or ipilimumab. Ongoing

GWN323

NCT02740270

I

Solid tumors and lymphomas

–

–

Ongoing

ICOS

JTX-2011

NCT02904226

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

NCT02723955

I

Solid tumors

–

–

Ongoing

MEDI-570

NCT02520791

I

NHL

–

–

Ongoing

4-1BB (CD137)

Utomilumab (PF-05082566)

NCT02179918

I

Solid tumors

6/23 patients CR or PR

No dose-limiting toxicities, most were grade 1–2 AEs

In combination with pembrolizumab

NCT01307267

I

NHL, NSCLC, RCC, HNSCC, melanoma

–

–

Alone or in conjunction with rituximab. Ongoing

NCT02444793

I

Solid tumors

–

–

In conjunction with mogamulizumab

NCT02315066

I

HNSCC, HCC, melanoma, RCC

–

–

In conjunction with OX40 Agonist PF-04518600

NCT02554812

II

Solid tumors

–

–

In conjunction with avelumab

Urelumab

NCT02253992

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

NCT01471210

I

Solid tumors and NHL

–

–

Completed

CD27-CD70

ARGX-110

NCT01813539

I

T cell lymphoma

2/9 patients had a reduction of malignant clones > 90%, 1 radiological PR and 2 skin PR

–

Ongoing

NCT01813539

I/II

CD70 positive malignancies

–

–

Ongoing

BMS-936561 (MDX-1203)

NCT00944905

I

RCC and B cell lymphoma

SD 69%

2/16 patients had grade 3 hypersensitivity

Completed

Varilumab

NCT02335918

I

Solid tumors

Not reported

1/33 patients developed a dose-limiting toxicity (hepatitis and kidney injury)

In conjunction with nivolumab

NCT02924038

I

Gliomas

–

–

Ongoing

NCT02302339

II

Melanoma

–

–

Ongoing

NCT02386111

I/II

RCC

–

–

Terminated (portfolio re-prioritization)

NCT02543645

I/II

Solid tumors

–

–

Terminated (portfolio re-prioritization)

CD40

CP-870893

NCT01103635

I

Melanoma

–

–

Ongoing

NCT02304393

I

Solid tumors

–

–

Ongoing

APX005M

NCT02482168

I

NSCLC, melanoma, urothelial cancer, HNSCC

–

–

Ongoing

NCT03165994

II

Esophageal and gastroesophageal tumors

–

–

Ongoing

NCT02706353

I/II

Melanoma

–

–

In conjunction with pembrolizumab. Ongoing

NCT03123783

I/II

Melanoma, NSCLC

–

–

In conjunction with nivolumab. Ongoing

ADC-1013

NCT02379741

I

Solid Tumors

–

–

Completed

NCT02829099

I

Solid Tumors

–

–

Ongoing

JNJ-64457107

NCT02829099

I

Solid tumors

–

–

Ongoing

SEA-CD40

NCT02829099

I

Solid tumors and lymphomas

–

–

Alone or in conjunction with pembrolizumab

RO7009789

NCT02304393

I

Solid tumors

–

–

Ongoing

NCT02588443

I

Pancreatic cancer

–

–

In conjunction with Nab-paclitaxel and gemcitabine. Ongoing

NCT02760797

I

Solid Tumors

–

–

In conjunction with Emactuzumab. Ongoing

NCT02665416

I

Solid Tumors

–

–

In conjunction with vanucizumab. Ongoing

Other pathways

IDO

BMS-986205

NCT02658890

I

Solid tumors

–

3/42 patients with grade 3 autoimmune hepatitis

In conjunction with nivolumab

Indoximod

NCT02073123

II

Melanoma

ORR 52%

No significant toxicities

Used in conjunction with ipilimumab, nivolumab, or pembrolizumab

NCT02077881

I/II

Pancreatic cancer

ORR 37%

1/30 patients with colitis

Used in conjunction with gemcitabine and nab-paclitaxel

NCT01560923

II

Prostate cancer

Median PFS increased from 4.1 to 10.3 months

No significant AEs

Ongoing

Epacadostat

NCT02327078

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

NCT02178722

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

NCT01195311

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

NCT02556463

I

Solid tumors

–

No severe AEs

In combination with durvalumab and radiation therapy

PG545 (pixatimod, pINN)

NCT02042781

I

Solid tumors

DCR 38%

3/23 patients developed dose-limiting toxicities

Completed

Polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC)

NCT00553683

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

NCT02983045

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

NCT02903914

I

Solid tumors

–

No dose-limiting toxicities

Alone and in conjunction with nivolumab

Oncolytic peptides

LTX-315

NCT01986426

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

NCT02009449

I

Melanoma

DCR 45%

11/25 patients with grade 3–4 AEs

In conjunction with pembrolizumab