Extended Data Fig. 3. (related to Sub-Heading, HSV1 serology predicts efficacy). Trial Survival Outcomes.
(a,b) Progression-free survival for the entire rHGG/rGBM group (a) and the 3 rHGG sub-groups divided by rGBM IDHwt, rAA IDHmut, and rAO IDH mutant (b), based on the 2021 WHO classification of central nervous system tumours5. (a) Kaplan Meier progression free survival (PFS) for all 41 subjects (42 interventions). Shaded region = 95% confidence interval of KM estimate of survival probability. The data is mature as of October 2022. The median PFS was 1.9 months (95% CI: 1.6 – 4.5). (b) Kaplan Meier PFS curves for 41 subjects, divided into rGBM IDH wild type (n = 32 subjects, 33 interventions), rAA IDH mutant (n = 4), and rAO IDH mutant (n = 5). The median PFS were 1.9 (95% CI: 1.6 – 4.6), 0.9 (95% CI: 0.5 - Inf) and 9.0 months (95% CI: 4.5 - Inf), respectively. The PFS HR for rAO IDH mut was 0.30 (95% CI, 0.10 – 0.86, p = 0.026 (CoxPH, 2-sided)) and PFS HR for rAA IDHmut was 2.63 (95% CI: 0.91 – 7.65, CoxPH p = 0.075 (CoxPH, 2-sided)). (c, d) Swimmer plots for Cohorts 1-9 (i.e., I-IX) (c) and Cohort 10 (i.e., X) (d). All 41 subjects’ (42 interventions, with subject 042/054 treated twice, 6 months apart) clinical course since day 0 CAN-3110 injection time is shown. Cohort number and CAN-3110 dose are indicated on the far left, with next column showing each subject clinical trial ID. Months after CAN-3110 injection is shown below. After CAN-3110 injection, subjects were followed and when there was MRI evidence of progression or pseudoprogression with or without clinical deterioration, additional treatments were instituted including craniotomy and/or biopsy. All instituted treatments (bevacizumab, immune checkpoint inhibitors, carboplatin, temozolomide, reirradiation, lomustine, LITT, targeted inhibitors) have shown no benefit in this setting in advanced trials and were used for palliative purposes. Post-CAN-3110 treatments are shown in colour coding on the far right and time/duration of treatment is overlaid on the swimmer plot for each subject. Below each bar, colour coding for dexamethasone dosing and duration is shown for each subject. As of September 2022, there are 4 surviving subjects (032, 048, 049, 051), 3 of which are IDH mutant anaplastic oligodendroglioma (1p/19q co-deleted) and one is IDH wt GBM (049).