The anticancer immunotherapy vaccine SL-701, when used with immunostimulants, induced antitumor activity in patients with relapsed/refractory glioblastoma both alone and in combination with bevacizumab, according to updated phase II results from the 2-stage STML-701-0114 trial presented at the 2018 ASCO Annual Meeting.
David Peereboom, MD
The anticancer immunotherapy vaccine SL-701, when used with immunostimulants, induced antitumor activity in patients with relapsed/refractory glioblastoma (GBM) both alone and in combination with bevacizumab (Avastin), according to updated phase II results from the 2-stage STML-701-0114 trial presented at the 2018 ASCO Annual Meeting.1
At a median follow-up of 10.9 months (range, 0.7-29.7), the objective response rate was 2% (1/46) in stage 1 and 14% (4/28) in stage 2. There were no complete responses (CR), 1 (2%) partial response (PR) and 13 (28%) patients with stable disease in stage 1. Two patients in stage 2 (7%) had CR and 2 (7%) had PR. Twenty-two (79%) had stable disease (SD).
The median overall survival (OS) in stage 1 was 11.0 months (95% CI, 8.2-12.0). The 12-month OS rate was 44% (95% CI, 28.9-58.9). In stage 2, the median OS was 11.7 months (95% CI, 7.1-not evaluable) and the 12-month OS rate was 50% (95% CI, 30.6-69.4).
Lead study author David Peereboom, MD, of Cleveland Clinic, et al said that 12-month OS in this population ranged from approximately 20% to 35% in previous trials.
“The SL-701 plus bevacizumab combination has been well-tolerated and has shown activity, including the emergence of long-term survivors comprised largely of target-specific CD8+ T cell responders,” Stemline Therapeutics CEO Ivan Bergstein, MD, said in a statement. SL-701, developed by Stemline, is a novel immunotherapy comprised of synthetic peptides targeting interleukin-13 receptor alpha-2, ephrin-A2, and survivin.
“Given the major unmet medical need in GBM and SL-701’s promising safety and efficacy data, we are considering next steps, including applying these immune data in registration-directed trial designs,” Bergstein added.
The 12-month OS rate among the target-specific CD8+ T cell responders was 75% in stage 2. The median OS was not reached.
A total of 74 bevacizumab-naïve patients received a median of 8.5 doses of SL-701 as of the February 2018 data cutoff date. In stage 1, patients received SL-701 along with adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) and imiquimod (Aldara) administered biweekly for 6 months, then every 28 days. In stage 2, SL-701 was administered along with adjuvant poly-ICLC and 10 mg/kg of bevacizumab biweekly for 6 months, then every 28 days.
Overall, 64.9% of patients were male and the median age was 57 years (range, 24-79). All 46 patients enrolled in stage 1 and 28 patients enrolled in stage 2 were evaluable for response.
Adult patients with HLA A-2positive GBM or WHO grade IV variants with KPS ≥70% were eligible if they had “unequivocal evidence of progression” following surgery, hypofractionated radiotherapy, or treatment with temozolomide (Temodar). Patients who had not undergone surgical resection were required to have measurable disease. Patients who had undergone surgical resection were eligible if they had no residual disease and no intermediate systemic therapy.
In stage 1, 2 patients had SD lasting ≥120 weeks and 1 had PR lasting >100 weeks. In stage 2, 1 patient had CR lasting >50 weeks and another had CR lasting roughly 40 weeks. One patient had PR lasting >60 weeks and another had PR lasting about 40 weeks. Seven patients had stable disease (SD) lasting >20 weeks.
There were no grade 4/5 adverse events (AEs) recorded and only 2 (2.7%) grade 3 treatment-related adverse events (TRAEs)fatigue in both cases.
The most common (≥10) any-grade TRAEs were fatigue (21.6%), injection site reaction (17.6%), injection site erythema (12.2%), and injection site pain (10.8%). The most common any-grade AEs were fatigue (39.2%), headache (32.4%), injection site reaction (20.3%), and nausea (20.3%).
Interim results from STML-701-0114 (NCT02078648) were presented at the 2016 Society for NeuroOncology Annual Meeting. At that point, the median duration of treatment was 1.9 months (range, 0.1 to ≥23) in the stage 1 group and 3.1 months (range, 0.9 to ≥10) in stage 2.2
There was 1 ongoing PR sustained for >13 months and 2 patients with ongoing SD lasting >18 and >20 months in stage 1. In stage 2, there were 2 CRs and 5 PRs. Two PRs and 1 CR were ongoing for ≥6 months. 1 patient with PR in stage 2 discontinued due to progression.
At a median follow-up of 4.1 months, the median progression-free survival was 5.6 months. The median OS was not reached.
Previous results from a phase I/II trial evaluating SL-701 for safety and immunogenicity were presented at the 2011 ASCO Annual Meeting.3
Patients with GBM (n = 13), anaplastic astrocytoma (n = 5), anaplastic oligodendroglioma (n = 3), or anaplastic oligoastrocytoma (n = 1) received SL-701 every 2 weeks for 4 injections along with 20 μg/kg of poly-ICLC administered twice weekly for 8 weeks.
Sixty-seven percent of patients with recurrent anaplastic glioma and 46% of those with recurrent GBM had tumor shrinkage or SD. One patient with recurrent GBM had sustained CR lasting ≥14 months.
The median overall survival (OS) was 12 months for patients with recurrent GBM. The 6-month OS was 80% and 12-month OS was 46%.
Thirteen of 16 (81%) patients had ≥1 positive immunogenicity assay.