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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
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)
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
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
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