Table 1.
Compilation of active or completed clinical trials investigating immunotherapeutic modalities in GBM, IDH mutant glioma, and pediatric DIPG/DMG diseases (2015–2020)
| Trial name | Treatment | Phase | Diagnosis | Outcomes |
|---|---|---|---|---|
| GBM: VACCINES | ||||
| ReACT NCT01498328 |
1) Rindopepimut/GM-CSF 2) Bevacizumab + KLH |
II (n = 73) | Recurrent EGFRvIII + GBM |
1) PFS-6: 28% 2) PFS-6: 16% (P = 0.12, one-sided) [66] |
| ACT IV NCT01480479 |
1) Rindopepimut/GM-CSF + TMZ 2) KLH + TMZ |
III (n = 745) | Newly diagnosed EGFRvIII + GBM |
1) mOS: 20.1 mos. 2) mOS: 20.0 mos. (HR = 1.01, 95% CI 0.79–1.30, P = 0.93) [7] |
|
IMA-950 |
IMA950 multi-peptide vaccine + poly-ICLC | I/II (n = 16) | Newly diagnosed, HLA-A2 + GBM | mOS: 19 mos. (95% CI: 17.25–27.87) [67] |
|
ICT-107 |
1) ICT-107 (peptide-pulsed DC vaccine) 2) Un-pulsed DCs |
II (n = 124) | Newly diagnosed GBM |
1) mOS: 17.0 mos. 2) mOS: 15.0 mos. (HR = 0.87, P = 0.58) [68] |
|
GAPVAC-101 |
1) APVAC1 or APVAC2 (multi-peptide vaccines)/GM-CSF + poly-ICLC + TMZ | I (n = 16) | Newly diagnosed, HLA-A*02:01 or HLA-A*24:02 + GBM |
mPFS: 14.2 mos. mOS: 29 mos. (for n = 15) (P = N/A) [69] |
|
DCVax-L |
1) DCVax-L (tumor lysate-pulsed DC vaccine) 2) PBMC (control) |
III (n = 348) | Newly diagnosed GBM |
mOS: 23.1 mos. (95% CI 21.2–25.4; P = N/A) [70] |
| NCT02078648 | SL701/GM-CSF + poly-ICLC and bevacizumab | I/II (n = 74) | HLA-A2 + recurrent GBM |
Stage 1 OS-12: 37% Stage 2 OS-12: 43% (P = N/A) [71] |
|
I-ATTAC |
CMV pp65-LAMP mRNA-pulsed DCs/GM-CSF/Td + TMZ | II (n = 48) | Newly diagnosed, CMV + MGMT unmethylated GBM | Recruiting |
|
ACTION |
TTRNA (tumor RNA) pulsed DCs/GM-CSF/Td ± HSCs | I (n = 8) | HGG | Recruiting |
| NCT01204684 | Tumor lysate-pulsed DCs ± resiquimod or poly-ICLC | II (n = 60) | New or recurrent HGG | Active |
| NCT03382977 | VBI-1901/GM-CSF | I/II (n = 38) | Recurrent, IDH-1/2 wildtype GBM | Recruiting |
| GBM: Checkpoint inhibitors | ||||
|
CheckMate 143 |
1) Nivolumab 2) Bevacizumab |
III (n = 626) | Newly diagnosed, first recurrence, or MGMT unmethylated GBM |
1) mOS: 9.8 mos. 2) mOS: 10.0 mos. (HR = 1.04; P = 0.76)[8•] |
|
CheckMate 498 |
1) Nivolumab + RT 2) TMZ + RT |
III (n = 550) | Newly diagnosed, MGMT Unmethylated GBM | Failure to reach primary objective of OS |
|
CheckMate 548 |
1) Nivolumab + TMZ + RT 2) TMZ + RT |
III (n = 693) | Newly diagnosed, MGMT Methylated GBM | Ongoing; failed to meet PFS primary endpoint; OS under investigation |
| NCT02337491 |
1) Pembrolizumab + bevacizumab 2) Pembrolizumab |
II (n = 80) | Recurrent GBM |
1) PFS-6: 26% mOS: 8.8 mos. 2) PFS-6: 6.7% mOS: 11.3 mos. [72] |
| NCT02313272 | Pembrolizumab + bevacizumab + HFSRT | I (n = 32) | Recurrent HGG |
OS-6: 94% OS-12: 64% [73] |
| NCT02794883 |
Durvalumab (anti-PD-L1) ± tremelimumab (anti-CTLA4) |
II (n = 36) | Recurrent HGG | Active |
| NCT02968940 | Avelumab (anti-PD-L1) + HFSRT | II (n = 43) | HGG | Completed |
| NCT02311920 | Ipilimumab + nivolumab + TMZ | I (n = 32) | Newly diagnosed GBM or gliosarcoma | Active |
| GBM: Adoptive cell therapy | ||||
| NCT02208362 | IL13Rα2-specific CAR T cells | I (n = 92) | Refractory/recurrent GBM |
Ongoing; interval analysis PFS (n = 1): 7.5 mos. [65] |
| NCT02209376 | EGFRvIII CAR T cells | I (n = 11) | Recurrent, EGFRvIII + GBM |
mOS: ~ 8 mos. PFS: not evaluable [61] |
| NCT01454596 | EGFRvIII CAR T cells, aldesleukin, fludarabine, and cyclophosphamide | I (n = 18) | New or recurrent, EGFRvIII + GBM |
mOS: 6.9 mos. PFS: 1.3 mos. Outlier: 12.5 mos. [62] |
|
HERT-GBM |
HER.CAR CMV-specific CTLs | I (n = 16) | Recurrent, HER2 + CMV seropositive GBM |
Ongoing; interim ORR (PR + SD): 33% [74] |
| NCT04077866 | B7-H3 CAR-T + TMZ | I/II (n = 40) | Recurrent or refractory GBM | Recruiting |
| NCT04045847 | CD147 CAR T cells | I (n = 31) | Recurrent CD147 + GBM | Recruiting |
| NCT04214392 | Chlorotoxin CAR T cells | I (n = 36) | Recurrent MPP2 + GBM | Recruiting |
| GBM: Viral therapy | ||||
|
DNX-2401 (Delta-24-RGD) |
DNX-2401 (adenovirus) 1) IT injection 2) IT infusion, resection |
I (n = 37) | Recurrent HGG |
1) mOS: 9.5 mos. 2) mOS: 13.0 mos. (P = N/A) [75] |
|
D24GBM |
DNX-2401 + TMZ | I (n = 31) | Recurrent GBM |
Ongoing; 3 objective responses (30, 19, and 27 mos.) [76] |
|
PVSRIPO |
1) Recombinant poliovirus 2) Historical controls |
I (n = 61) | Recurrent GBM |
1) mOS: 12.5 mos. (95% CI, 9.9 to 15.2) 2) mOS: 11.3 mos. (95% CI, 9.8 to 12.5) (P = N/A) [77] |
| NCT02986178 | PVSRIPO + lomustine | II (n = 122) | Recurrent GBM | Active |
| NCT01156584 |
1) Toca 511 + Toca FC 2) External control |
I (n = 54) | Recurrent, unresectable HGG |
1) mOS: 13.6 mos. 2) mOS: 7.1 mos. |
| NCT01470794 | Toca 511 + Toca FC | I (n = 56) | Recurrent HGG | mOS: 11.9 mos. (95% CI, 10.7 to 15.1) [80] |
| NCT02414165 |
1) Toca 511 + Toca FC 2) SOC |
II/III (n = 403) |
Recurrent HGG; IDH-mut stratified |
1) mOS: 11.1 mos. 2) mOS: 12.2 mos. (HR = 1.06; P = 0.6154) [6] |
|
rQNestin |
rQNestin34.5v.2 HSV-1 ± cyclophosphamide | I (n = 108) | Recurrent HGG | Ongoing |
| UMIN000002661 | G47delta (2nd-gen. oncolytic HSV-1) | I-II (n = 21) | Recurrent GBM |
Completed No results reported yet |
| UMIN000015995 |
1) G47delta 2) Historical control |
II (n = 30) | Recurrent GBM |
Ongoing 1) OS-12: 92.3% 2) OS-12: 15% [81] |
| NCT00390299 |
MV-CEA (measles virus) 1) IC injection 2) IT infusion + resection + IC injection |
I (n = 23) | Recurrent GBM |
1) mOS: 11.8 mos. PFS-6: 22.2% 2) mOS: 11.4 mos. PFS-6: 23.1% [82] |
|
ParvOryx01 |
H-1PV (H-1 parvovirus) | I/IIa (n = 18) | Progressive primary or recurrent GBM patients |
mOS: ~ 15.5 mos. PFS: ~ 4 mos. (P = N/A) [83] |
| GBM: Combination therapies (not including SOC) | ||||
|
Ad5-DNX-2401 |
Ad5-DNX-2401 (adenovirus delivered in MSCs) | I (n = 36) | Recurrent, IDH-1 wildtype HGG/AAs | Ongoing |
| NCT03726515 | EGFRvIII-targeted CAR-T + pembrolizumab | I (n = 7) | Newly diagnosed MGMT Unmethylated, EGFRvIII + GBM | Ongoing |
| NCT04003649 | IL13Rα2 TN/MEM cells, ipilimumab and nivolumab (neoadjuvant, adjuvant) | I (n = 60) | Recurrent or refractory GBM | Recruiting |
|
NeoVax |
NeoAntigen (multi-peptide vaccine), RT, pembrolizumab | I (n = 46) | Newly diagnosed MGMT Unmethylated GBM | Ongoing |
|
CAPTIVE/KEYNOTE-192 |
DNX-2401, pembrolizumab | II (n = 49) | Recurrent GBM patients |
Ongoing; interim analysis: OS-9: 100% (first 7 patients) [84] |
| NCT04013672 | Pembrolizumab, SurVaxM (survivin vaccine)/GM-CSF, Montanide ISA 51 | II (n = 51) | Recurrent GBM | Recruiting |
|
IMA950-106 |
Pembrolizumab + IMA950/poly-ICLC | I (n = 24) | Recurrent GBM | Ongoing |
| NCT03743662 | Bevacizumab, nivolumab, RT, re-resection | II (n = 94) | Recurrent, IDH wildtype GBM | Recruiting |
|
MEDI4736 |
Durvalumab ± RT or bevacizumab | II (n = 159) | Newly diagnosed or recurrent MGMT Unmethylated GBM | Active |
| NCT03425292 | Nivolumab ± ipilimumab ± bevacizumab ± TMZ | I (n = 90) | Newly diagnosed HGG | Recruiting |
| NCT04225039 | SRS + GITR agonist (INCAGN01876) + anti-PD1 (INCMGA00012) | II (n = 32) | Recurrent, IDH wildtype GBM | Recruiting |
| NCT01811992 |
Ad-hCMV-tk and Ad-hCMV-Flt3L (adenoviral vectors) |
I (n = 19) | Newly diagnosed GBM | Ongoing |
| NCT03576612 | AdV-tk + valacyclovir + nivolumab + RT + TMZ | I (n = 36) | Newly diagnosed HGG | Recruiting |
| GLOBE NCT02511405 |
1) VB-111, bevacizumab 2) Bevacizumab |
III (n = 256) | Recurrent GBM |
1) mOS: 6.8 mos. 2) mOS: 7.9 mos. (HR, 1.20; 95% CI: 0.91–1.59; P = 0.19) [85] |
|
DNX-2440 |
DNX-2440 (OX40L adenoviral vector) | I (n = 24) | Recurrent GBM | Ongoing |
|
M032-HSV-1 |
M032-HSV-1 (2nd-gen. HSV) with IL-12 | I (n = 36) | Recurrent GBM | Ongoing |
| IDH mutant glioma: Vaccine | ||||
| RESIST NCT02193347 | IDH peptide vaccine (PEPIDH1M) + TMZ | I (n = 24) | Recurrent Grade II glioma, IDH mutant | Ongoing |
|
NOA-16 |
IDH1R132H peptide vaccine, montanide, imiquimod |
I (n = 39) | Newly diagnosed AA and GBM; IDH1R132H mutant | 80% specific T cell response; 87% with specific humoral response [86] |
| IDH mutant glioma: Combination therapy | ||||
| NCT03532295 | INCMGA00012 (anti-PD1) + epacadostat + bevacizumab + RT | II (n = 55) |
Recurrent GBM IDH wildtype or mutant |
Recruiting |
| NCT03422094 | NeoVax, ipilimumab, nivolumab | I (n = 3) | Newly diagnosed MGMT Unmethylated, IDH1/IDH2 mutant GBM | Ongoing |
| Pediatric: Adoptive cell therapy | ||||
| NCT04196413 | GD2-CAR T cells | I (n = 54) | DMG with H3.3 K27M mutation | Recruiting |
| NCT04185038 | B7H3-CAR T cells | I (n = 70) | DMG, or recurrent CNS tumor | Recruiting |
| NCT03389230 | HER2(EQ)BBζ/CD19t+ T cells | I (n = 42) | Recurrent, HER2 + HGG | Recruiting |
| NCT03500991 | I (n = 48) | Refractory or recurrent, HER2+ pediatric CNS tumor | Recruiting | |
| NCT03638167 | EGFR806-CAR T cells | I (n = 36) | EGFR + refractory or recurrent CNS tumor | Recruiting |
| Pediatric: Vaccine | ||||
| NCT02960230 | H3.3 K27M peptide vaccine ± nivolumab | I (n = 29) | New glioma with H3.3 K27M mutation | Ongoing [56] |
|
BRAVO |
TTRNA (tumor RNA) pulsed DCs/GM-CSF/Td + HSCs + TMZ or cyclophosphamide/fludarabine | I (n = 21) | DMG | Recruiting |
| Pediatric: Immune checkpoint inhibition | ||||
| NCT04323046 | Neoadjuvant ipilimumab ± nivolumab | I (n = 45) | Recurrent HGG | Not yet recruiting |
| Pediatric: Viral therapy | ||||
| NCT03178032 | DNX-2401 + SOC | I (n = 12) | Naïve DIPG |
Completed No results reported yet |
| NCT03043391 | PVSRIPO | I (n = 12) | Recurrent HGG | Recruiting |
| NCT03911388 | HSV-G207 | I (n = 15) | Recurrent GBM and CNS tumors | Recruiting |
| Pediatric: Combination therapy | ||||
| NCT00634231 | AdV-tk plus valacyclovir + RT | I (n = 12) | Malignant glioma or recurrent ependymoma |
Active OS (n = 3): 24+ mos. PFS (n = 2): 37.3 and 47.7 mos. [87] |
Clinical trial information was found on www.clinicaltrials.gov accessed August 5, 2020. IV intravenous, mOS median overall survival, PFS-# progression free survival-number of months, OS-# overall survival-number of months, CI confidence interval, HR hazard ratio, ORR overall response rate, PR partial response, SD stable disease, SOC standard of care, TMZ temozolomide, KLH keyhole limpet hemocyanin, DC dendritic cell, IT intratumoral, IC intracavitary, RT radiotherapy, HFSRT hypofractionated radiation therapy, Td tetanus diphtheria toxoid, HSCs hematopoietic stem cells, MSCs mesenchymal stem cells, SRS stereotactic radiosurgery, DIPG diffuse intrinsic pontine glioma