Table 1 Overview of peer-reviewed published results of clinical GBM trials involving poly-ICLC
Author Year Trial ID | Diagnosis (na) Phase | Treatment following diagnosis | Poly-ICLC | Safety | Immunomonitoring | Clinical effects For GBM patients unless specified otherwise |
|---|---|---|---|---|---|---|
Poly-ICLC in non-vaccination trials | ||||||
Salazar 1996 n.r. | ND (18/38) & Rec (9b/38) Pilot (I/II) | / or CT | 10-50 μg/kg IM 1-3x/w alone or concurrent | Very well tolerated, = QoL | Serum: ↗↗ IFN (4/15), variable neopterin and IL-2, = TNF-α and IL-6 | ND GBM: mOS 11mo (1x/w), 19mo (2-3x/w); 1 CR, 2 PR, 6 SD, 8 PD; 8/12 ≥ SD if 2-3x/w recGBM: mOS 15mo-19mo (w-w/o CT) |
Butowski 2009 NCT00052715 | ND (30) II | Surgery + RT | 20 μg/kg IM 3x/w, concurrent + adjuvant | Very well tolerated, = QoL 15 AE3 + 1 AE4 | n.r. | Study vs ctrl (RT + nonTMZ-CT) vs ctrl (RT): 12mo OS: 69.4 vs 57 vs 35% mOS: 15.0 vs 13.1 vs 9.2mo Study: 30 and 5% 6mo and 1y PFS, 18w TTP |
Rosenfeld 2010 NCT00262730 | ND (97) II | Surgery + Stupp | 20 μg/kg IM 3x/w, concurrent (w2–8/cycle TMZadj) | Attributed to poly-ICLC: 1 AE3 + 0/15 AE4 (−/+ TMZ) + 0/2 deaths | n.r. | Entire cohort vs 18-70y old cohort vs Stupp: mOS 17.2mo vs 18.3mo vs 14.6mo 12mo OS 73.2 vs 79.5 vs 61.1% 18mo OS 47.4 vs 51.8 vs 39.4% 24mo OS 29.9 vs 32.5 vs 26.5% Failure (death) HR 0.46 vs n.d. vs 0.63 |
Hartman 2014 n.r. | Rec, pediatric (12b/32) II | / | 20 μg/kg IM 2x/w in 4w-cycles (until 2y) | Very well tolerated 16 AE3 + 3 AE4 (entire cohort) | n.r. | RecHGG: 1 PR (recAA), 1 SD, 1 response; 3/12 response rate overall |
Poly-ICLC as cancer vaccine adjuvant | ||||||
Okada 2011 NTC00766753 | Rec (13/22) I/II | GAA-loaded αDC1, IN Initiation (1-12w): 1x/2w Booster 1 (13-29w): 1x/4w Booster 2 (30w-3y): 1x/3mo | 20 μg/kg IM, concurrent Initiation: 2x/w (w1–8) Booster 1: 2x/w Booster 2: 1x/w | ≤ AE2 | 8/12 functional GAA-specific CD8+ T-cell response ↗ Type 1 cytokines & chemokines | 1 CR, 1 PR, 9 SD mOS 12 mo mTTP 4mo 12mo PFS 30.8% |
Prins 2011 NTC00068510 | ND & Rec (11/23) I | ND: Surgery + Stupp; Rec: Surgery + Stupp + Surgery Autologous tumor lysate-pulsed DC, ID Initiation: 3x biweekly, before TMZadj Booster: 1x/3mo in between TMZadj cycles | / | ≤ AE2 | ↗ Serum Th1 cytokines, ↗ Th1/Th2 cytokine ratio = Tregs; ↗ CD8+ TIL in mesenchymal group | ↗ OS with DC vaccine vs controls in mesenchymal group; = OS in proneural group mOS 17.3 (DC only) vs ≥ 22.3mo (DC + poly-ICLC) |
ND & Rec (3/23) I | 20 μg/kg IM, concurrent (boosters) | ≤ AE2 | Log-fold ↗ serum Th1 cytokines | |||
Pollack 2014 NCT01130077 | ND, pediatric (5/26) Pilot | Surgery + Stupp (no TMZadj) GAA in Montanide ISA-51, SC Initiation: 8x, every 3w Booster: every 6w until 2y | 30 μg/kg IM, concurrent (vaccine) | ≤ AE2 | ELISPOT (3/5): 3/3 response to 2/3 GAA, 2/3 to GAA + Tet | 2 CR, 1 PR, 2 SD mOS ≥14.7mo |
Pollack 2016 NCT01130077 | Rec, pediatric (6/12) Pilot | Various regimens GAA in Montanide ISA-51, SC Initiation: 8x, every 3w Booster: every 6w until 2y | 30 μg/kg IM, concurrent (vaccine) | ≤ AE2 | ELISPOT (5/6): 5/5 response to ≥1 GAA, 2/5 to all GAA + Tet, 3/5 only to 1 GAA | 1 PR, 2 SD, 3 PD mOS 14.25mo mPFS 1.8mo |
Hilf 2018 NTC02149225 | ND (15) I | Surgery + Stupp Personalized GAA vaccines APVAC1 + APVAC2, ID (+GM-CSF) during TMZadj APVAC1: pre-manufactured unmutated antigens, 11x APVAC2: neo-epitopes, 8x | 1.5 mg SC, concurrent (vaccine) | 6 > AE2 due to APVAC1/2, poly-ICLC and/or GM-CSF | APVAC1: 12/13 persistent response to ≥1 APVAC1-GAA, ↗ % AVPAC1-reactive memory T cells; ↗ PD-1; 9/13 Th1 CD4+ T cell response to ≥1 pan-DR antigens APVAC2: 8/10 neo-GAA-specific, CD4+ T cell response to APVAC2; 11/13 mutated APVAC2-GAA induced CD4+ T cell response (Th1 and multifunctional); no isolated CD8+ T-cell response | mOS 29.0mo mPFS 14.2mo |
Keskin 2019 NCT02287428 | ND, MGMT-unmethylated (8) I/Ib | Surgery + Stupp (no TMZ) Multi-epitope personalized neo-GAA vaccine Priming: 5x Booster: 2x | 0.5 mg SC, admixed (vaccine) | ≤ AE2 | If no DEX during vaccination priming (2/8): IFN-γ response by polyfunctional neo-GAA-reactive T cells Generation of GAA-experienced memory T cells At relapse: ↗ CD8+ TIL, ↘ Treg. GAA-specific TCR-α and -β clonoypes found ↗ CD8+PD-1+ T cells | All patients died from PD mOS 16.8mo mPFS 7.6mo |
Migliorini 2019 NCT01920191 | ND (6) I/II | Surgery + Stupp IMA950 multi-GAA vaccine, ID Before and between TMZadj cycles | 1.5 mg IM, concurrent (vaccine) | 1 AE3 + 1 AE4 due to vaccine and/or poly-ICLC | Concurrent: ↘ specific T-cell response, ↘ immunization efficacy Admixed (SC/IM): ↗↗↗ immunization efficacy; ↗↗↗ mono & multiple GAA-specific CD4+ and CD8+ T-cell responses; durable type I cytokine secretion from 1st vaccination GAA-specific TIL in 0/5 tumor samples after vaccination GBM cohort: 62.5 and 31.3% CD8+ T-cell response to 1 and > 1 GAA | Concurrent: 2 SD, 4 PD Admixed, SC: 1 CR, 5 PD Admixed, IM: 2 PR, 1 SD, 1 PD GBM cohort: mOS 19mo mPFS 9.5mo 6mo PFS 69% 9mo PFS 56% |
ND (6/7) I/II | 1.5 mg SC, admixed (vaccine) | |||||
ND (4/6) I/II | 1.5 mg IM, admixed (vaccine) | |||||
Boydell 2019 NCT01920191 | Rec (35/40) I/II post-hoc | Surgery + Stupp + Surgery 2nd line: bevacizumab, 10 mg/kg IV every 2–3 weeks | / | n.r. | n.r. | OS and PFS = between cohorts |
Rec (14/16) I/II post-hoc | Surgery + Stupp + IMA950 vaccine + Surgery 2nd line: bevacizumab, 10 mg/kg IV every 2–3 weeks | 1.5 mg, admixed (IMA950 vaccine) | ||||
Wang 2020 NCT02709616 NCT02808364 | ND GBM (3/5) Rec GBM (2/5) I | ND: Surgery + Stupp Rec: Surgery + Stupp + surgery GAA-loaded DC, ID/IV (+ CPM + imiquimod) 1 week after surgey | 50 μg/kg poly(I:C) IM, concurrent (every 2 days for 2 weeks per vaccination) | ≤ AE2 | ↗ GAA-specific CD4+ and CD8+ T cells in 3/3 | mOS 19mo (vs 11mo) |