Table 1.
Recent Randomized Phase 3 Clinical Trials of Immunotherapy in GBM
| Trial/Treatment Name, Agent, Year of Publication | Targeted Tumor | Trial Type | Design | Efficacy | Serious Adverse Events | Additional Results |
|---|---|---|---|---|---|---|
| ACT IV, Rindopepimut, EGFRvIII peptide vaccine linked to KLH (2017) | Newly diagnosed EGFRvIII+ GBM | RCT, double-blind, multicenter | Maximal surgical resection and standard chemoradiation without progression. Then randomized 1:1 Rindopepimut + TMZ (n = 371) vs. KLH placebo + TMZ (n = 374), administered intradermally. | Study terminated for futility after preplanned interim analysis due to no significant difference in mOS | Seizures, brain edema, pulmonary embolus | - Robust humoral responses in the Rindopepimut group. - EGFRvIII expression after treatment undetectable in 57% of Rindopepimut and 59% of control patients |
| Toca511/FC, replicating retrovirus that delivers yCD to sensitize tumors to 5-FC (2020) | First or second recurrence of GBM or AA. | RCT, open-label, multicenter | Randomized at time of resection 1:1 to Toca511/FC (Toca511 administered in tumor cavity followed by intravenous 5-FC, n = 201) or SOC (investigator choice of lomustine, TMZ, or Bev, n = 202) | No significant difference in mOS in the ITT population. | Neurologic deficits | - Patients at second recurrence or with AA or with IDHmut with possible improved mOS - IDHmut tumors with higher baseline levels of immune cells and less immunosuppressive cells. - Median cycles of 5-FC posttreatment were only two. due to tumor progression. |
| Checkmate 143, nivolumab, (2020) | First recurrence of GBM after standard chemoradiation | RCT, open-label, multicenter | Randomized after chemoradiation to nivolumab (n = 184) or bevacizumab (n = 185) | No significant difference in mOS | No significant safety events attributable to nivolumab alone | - Hazard ratio for patients with no baseline steroid use was lower for the nivolumab group. - mOS was increased in patients with no baseline steroids and methylated MGMT promoter |
| Checkmate 498, nivolumab (2022) | nGBM with unmethylated MGMT promoter | RCT, open-label, multicenter | Randomized to nivolumab + RT (n =280) or TMZ + RT (n = 280) | Statistically significant survival benefit of SOC TMZ + RT over nivolumab + RT | Cerebral edema, suddent death, respiratory failure | - PD-L1 expression did not predict responses. |
| Checkmate 548, nivolumab (2022) | nGBM with methylated MGMT promoter | RCT, open-label, multicenter | Randomized to nivolumab + RT + TMZ (n = 355) or Placebo + TMZ + RT (n = 354) | No significant difference in mOS or mPFS | Respiratory failure/distress, pancytopenia, pneumonia | - PD-L1 expression did not predict responses |
| DCVax-L, Autologous DCs loaded with tumor lysates (2022) | N and rGBMs | Prospective, externally controlled nonrandomized multicenter | DCVax-L + SOC (n = 232) vs. contemporaneous matched external controls treated with SOC (n = 99)A | Increase in mOS for treatment compared to controlA | Cerebral edema | - tail of long-term responders |
ARefer to main text regarding limitations of design and data analyses/interpretation.