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Table 2 Summary of ongoing phase I, I/II, and II clinical trials utilizing immune checkpoint inhibition therapy

From: Next generation of immune checkpoint inhibitors and beyond

Category

Target

Drug

Trial

Phase

Type of tumor

Clinical efficacy

Safety

Comments

Inhibitory immune checkpoint targets

LAG-3 (CD223)

LAG525 (IMP701)

NCT02460224

I/II

Advanced malignancies

11/121 patients in the combination group achieved PR

1 patient had a CR

DLTs occurred in 4/121 patients included grade 3 and 4 pneumonitis, acute kidney injury, and autoimmune hepatitis

With or without spartalizumab

   

NCT03365791

II

Solid or hematologic malignances

DCR for neuroendocrine tumors (86%), diffuse large B cell lymphoma (43%), and small cell lung cancer (27%)

11/72 patients had grade 3 or 4 AEs including dyspnea, fatigue, and poor appetite

In combination with spartalizumab

  

REGN3767 (R3767)

NCT03005782

I

Solid or hematologic malignances

Monotherapy group: ORR 0% and DCR 48% with 12 SD

Combination group: ORR 5% and DCR was 31% with 2 PR and 11 SD

2/12 PR and 6 SD in the group crossed over from monotherapy to the combination

1/67 DLT in the combination group (G4 CK elevation + G3 myasthenic syndrome + G1 elevation of troponin

Alone or in combination with cemiplimab

  

BI 754,091

NCT03156114, NCT03433898, NCT03780725

I

Advanced or metastatic solid tumors

Not reported

21/321 DLTs, particularly infusion-related reactions (n = 6). Serious AEs: 77/321 (27%): pleural effusion (n = 6), deep venous thrombosis (n = 4), cardiac tamponade (n = 1), and acute kidney injury (n = 1)

Used in combination with anti-PD-1 therapy

   

NCT03697304

II

    
  

Tebotelimab (MGD013)

NCT03219268

I

Advanced or metastatic solid or hematologic malignancies

Dose escalation (n = 29): ORR 10% and DCR 55% with 3 confirmed PR, 1 unconfirmed PR, and 13 SD

Expansion cohort (n = 41): ORR 7%, DCR 59% with 3 PR, and 21 SD

2/207 DLTs: immune-mediated hepatitis and increased lipase

Alone or in combination with margetuximab (for patients who had expression of HER2 on their tumors)

  

Eftilagimod alpha (IMP321)

NCT02676869

I

Advanced melanoma

1/18 CR

No DLTs reported

Used with pembrolizumab

   

NCT03252938

I

Advanced solid tumors

ORR 17% and DCR 33% with 1/6 PR, 1/6 SD, and 4/6 PD

No DLTs reported

Used with avelumab

   

NCT03625323

II

Advanced or metastatic NSCLC and HNSCC

ORR 47% and DCR 82% with 8/17 PR and 6/17 SD

Most common toxicities included cough (31%), fatigue (19%), and diarrhea (15%)

Used with pembrolizumab

  

FS118

NCT03440437

I

Advanced solid tumors

  

Ongoing

 

TIM-3

MBG453

NCT02608268

I/II

Advanced solid tumors

ORR in the monotherapy group was 0% and DCR was 29% with 25/87 SD

ORR in the combination group was 5% and DCR was 44% with 4/86 PR and 34/86 SD

One DLT in combination cohort (grade 4 MG)

11% developed grade 3 or 4 AEs in the combination cohort

Combined with spartalizumab

  

Sym023

NCT03489343

I

Advanced solid tumors and lymphomas

No results available

  

TSR-022

NCT02817633

I

Advanced solid tumors

Ongoing

 

B7-H3 and B7-H4

MGC018

NCT03729596

I/II

Advanced solid tumors

ORR 0% and DCR 15% with 3/20 SD

1 DLT: grade 4 neutropenia

3 serious AEs: pneumonitis, gastroenteritis, stasis dermatitis

Used as monotherapy

  

FPA150

NCT03514121

I

B7-H4 positive solid malignancies

ORR 3% and DCR 38% with 1/29 PR and 10/29 SD

No DLTs or grade 4/5 toxicities were reported

Used as monotherapy

 

A2aR

EOS100850

NCT02740985

I

Advanced solid tumors

ORR 0% and a DCR of 29% with 6/21 SD

No DLTs and no grade 3 or 4 AEs

Used as monotherapy. First in human

  

AB928

NCT03719326

NCT03720678

NCT03629756

I

Advanced solid tumors

ORR 4% and DCR of 27% with 1/26 PR and 6/26 SD

1 DLT: grade 1 rash

6 patients with grade 3 or 4 AEs: fatigue, nausea, and cytopenias

Used in combination with standard chemotherapy or anti-PD-1 therapy

 

CD73

CPI-006

NCT03454451

I

Advanced solid tumors

1 patient (monotherapy) with metastatic CRPC: substantial reduction in the size of a target lesion after only 5 cycles, sustained at the time of cutoff

No DLTs reported

Used as monotherapy or in combination with an anti-A2aR agent (CPI-444)

 

NKG2A

Monalizumab

NCT03088059

II

Platinum-resistant, recurrent or metastatic, HNSCC

PFS: 7.4 weeks

Median OS: 27.7 weeks

ORR 0%, DCR 22% with 6/27 SD

No DLTs reported

Used as monotherapy

   

NCT02643550

II

Platinum-resistant, recurrent or metastatic, HNSCC

ORR 20%

DCR 58% with 8/40 PR 15/40 SD

No DLTs reported

Used in combination with cetuximab

 

PVRIG/ PVRL2

COM701

NCT03667716

I

Advanced Solid tumors

DCR 57% (16/28 patients)

No CRs

1/16 PR in the monotherapy group 1/12 unconfirmed PR in the combination group

No DLTs reported

Used as monotherapy and in combination with nivolumab

Inhibitory targets beyond immune checkpoints

CEACAM1

CM24

NCT02346955

I

Advanced or recurrent solid tumors

ORR of 0% and a DCR of 30% with 8/27 SD

Median OS 4 months (lower dose), and 6 months (higher dose)

No DLTs

4 individuals with grade 3–4 GGT elevation

Used as monotherapy

 

CEACAM 5/6

NEO-201

NCT03476681

I

Advanced solid tumors

ORR 0% and DCR 33% with radiological SD in 3/9 patients

No DLTs reported

Used as monotherapy

 

FAK

Defactinib

NCT02546531

I

Advanced pancreatic adenocarcinoma

Escalation cohort (n = 8): ORR 13% and DCR 50% with 1 PR, 3 SD, and 4 PD

Expansion cohort (= 20): ORR 5% and DCR 60% with 1 PR, 11 SD, 7 PD and 1 non-evaluable response

No DLTs were seen

Most common grade 1 and 2 AEs included fatigue, anorexia, nausea, and vomiting

Used in combination with pembrolizumab and gemcitabine

 

CCL2/ CCR2

PF-04136309

NCT02732938

I

Metastatic pancreatic adenocarcinoma

ORR 23.8%, DCR 38% with 0/21 CR, 5/21 confirmed PR, 1/21 unconfirmed PR, and 3/21 SD

DLTs: dysesthesia, hypokalemia, and hypoxia

24% pulmonary toxicities including 3 patients with grade 3 pneumonitis, 1 grade 4 hypoxia, and 1 grade 5 pneumonia

Used in combination with nab-paclitaxel and gemcitabine

 

LIF

MSC-1

NCT03490669

I

Advanced solid tumors

DCR 22% with 9/41 SD lasting > 16 weeks

No DLTs reported

Used as monotherapy

 

CD47/ SIRP

Hu5F9-G4 (5F9)

NCT02216409

I

Advanced Solid tumors

ORR ~ 5%

DCR 19% with 2/43 PR (ovarian and fallopian tube cancers) and 6/43 SD (CRC)

AEs occurred with higher doses. These included constitutional symptoms (50%), headache (34%), anemia (39%), and lymphopenia (28%)

Used as monotherapy

   

NCT02953509

I/II

Relapsed and refractory NHL

CRR 21%

ORR 49% with 16/75 CR and 21/75 PR

DLTs 4% (no specifics provided)

Combined with rituximab

  

ALX148

NCT03013218

I

Advanced solid tumors or refractory NHL

ICI-naïve HNSCC: ORR 40% (4/10), median PFS 4.6 months, and median OS not reached after 14 months of follow-up

Non-ICI-naïve HNSCC: ORR 0%, median PFS 2 months, median OS 7.4 months

ALX148 + trastuzumab in gastric/gastroesophageal cancers (n = 20): ORR 20%, median PFS 2.2 months, and median OS 8.1 months

Monotherapy (n = 25): DCR 16% with 4/25 SD

2 DLTs: neutropenia with infection and thrombocytopenia with a significant bleed

1 grade 5 (fatal) toxicity under investigation

Most AEs (66%) were low grade

Used in monotherapy agent or with pembrolizumab, trastuzumab, rituximab, ramucirumab, 5FU, paclitaxel, or cisplatin

  

TTI-662

NCT03530683

I

Relapsed or refractory lymphomas

1 patient (DLBCL) with 5 prior lines of therapy achieved a PR by week 8 and a CR by week 36

No DLTs

Used as monotherapy

  

RRx-001

NCT02518958

I

Advanced solid malignancies or lymphomas

ORR 25%, DCR 67% with 3/12 PR, 5/12 SD, and 3/12 PD

No DLTs reported

1 patient discontinued therapy due to pneumonitis

Used in combination with nivolumab

 

CSF-1

(M-CSF)/ CSF-1R

Lacnotuzumab (MCS110)

NCT02807844

I/II

Advanced malignancies

DCR 27%

3/48 had pancreatic cancer: 1 PR, and 2 SD lasting > 300 days

No DLTs reported

Used in conjunction with spartalizumab

  

LY3022855

NCT02265536

I

Metastatic BC and metastatic CRPC

BC (n = 22): DCR 23% with 5/22 SD. 2 of these had a response that lasted > 9 months

CRPC (n = 7): ORR 0% and DCR 43% with 3/7 SD lasting up to 4 months

No DLTs reported

Used as monotherapy

  

SNDX-6352

NCT03238027

I

Advanced solid tumors

DCR 13% with 4/32 SD that lasted > 4 months

2 DLTs, one grade 3 fatigue and one grade 3 pneumonitis

Used as monotherapy and in combination with durvalumab

  

Emactuzumab (RG7155)

NCT01494688

I

Advanced solid tumors

Monotherapy (n = 99): ORR 0% and DCR 13% with 13/99 SD

Combination (n = 54): ORR 7% DCR 50% with 4/54 PR 23/54 SD

No DLTs in the monotherapy, 2 DLTs in the combination: one grade 4 hypokalemia and one grade 3 hemorrhagic enterocolitis

One grade 5 AE: bowel perforation

Used as monotherapy or in combination with paclitaxel

  

Pexidartinib (PLX3397)

NCT01525602

I

Advanced solid tumors

ORR 16%, DCR 50%, PD rate 45% with 1/38 CR, 5/38 PR, 13/38 SD, and 17/38 PD

2 DLTs: one grade 3 atrial fibrillation and one grade 3 hypophosphatemia

Used in combination with paclitaxel

   

NCT02777710

I

Advanced or metastatic pancreatic adenocarcinoma or CRC

ORR 0% and DCR 21% with 4/19 SD

2 DLTs: both transaminase elevation, one with hyperbilirubinemia

Used with durvalumab

   

NCT02734433

I

Asian patients with symptomatic, advanced solid malignancies

DCR 67% with 1/11 PR and 4/11 SD

5 patients experienced at least one grade 3 or 4 AE: elevated transaminases and anemia

Monotherapy

 

IL-1 and IL-1R3

(IL-1RAP)

CAN04

NCT03267316

I

Advanced or metastatic NSCLC, CRC, BC, or pancreatic adenocarcinoma

DCR 45% with 9/22 SD including 2 whose response lasted > 4 months

No DLTs or grade 4–5 AEs reported

Used as monotherapy

  

Canakinumab (ACZ885)

NCT03968419

II

Early-stage NSCLC

Ongoing

 

IL-8

BMS-986253

NCT02536469

I

Advanced solid tumors

ORR 0% and DCR 73% with 11/15 SD and 4/15 PD

No DLTs reported

Used as monotherapy

   

NCT03400332

I/II

Advanced solid tumors

Ongoing

 

SEMA4D

Pepinemab (VX15/2503)

NCT03268057

I/II

Advanced-stage NSCLC

Immunotherapy-naïve (n = 21): ORR 24% and DCR 81% with 5/21 PR and 12/21 SD

Immunotherapy-refractory (n = 29): ORR was 7% and DCR was 59% with 2 patients achieving PR and 15 SD

No DLTs reported

Used in combination with avelumab

 

Ang-2

Trebananib

NCT03239145

I

Advanced solid tumors

DCR 33% and ORR 7% with 1/15 PR and 4/15 SD

Median time to progression: 2.6 months

OS: 11.4 months

No DLTs and no grade 3 or 4 AEs

Used in combination with pembrolizumab

 

CLEVER-1

FP-1305

NCT03733990

I/II

Advanced solid tumors

ORR 3% and DCR 27% with 2/30 PR, 6/30 SD, and 22/30 PD

No DLTs reported

Used as monotherapy

 

Axl

Enapotamab vedotin (EnaV)

NCT02988817

I

Advanced solid tumors

ORR 6%, DCR 55% with 3/47 PR and 26/47 SD

6 DLTs: constipation, vomiting, GGT elevation, febrile neutropenia, and diarrhea

First-in-human clinical trial. Used as monotherapy

 

Phosphatidylserine

Bavituximab

NCT01264705

II

Advanced, unresectable HCC

ORR 5%, DCR 58% with 2/38 PR and 20/38 SD

No DLTs or grade 4–5 AEs reported

Used in combination with sorafenib

  1. AE, adverse event; BC, breast cancer; CK, creatine kinase; CR, complete response; CRC, colorectal cancer; CRR, complete response rate; CRPC, castrate-resistant prostate cancer; DCR, disease control rate; DLT, drug-limiting toxicities; GGT, Gamma-glutamyl transaminase; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; ICI, immune checkpoint inhibitor; MG, Myasthenia Gravis; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung carcinoma; OR, objective response; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; SIRP, signal regulatory protein