First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Category: Studies

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Summary

This trial aims to evaluate the addition of an autologous tumor lysate-pulsed Dendritic Cell vaccine (DCVax®-L) to standard therapy for patients diagnosed with glioblastoma. The findings suggest the addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.

Patients characteristics

Methodology

All patients underwent surgical resection and 6 weeks of chemoradiotherapy per SOC, prior to enrollment and randomization in the study. Patients were randomized 2:1 to SOC plus autologous DC vaccine (DCVax-L; n=232) or SOC plus placebo (n=99). PBMCs were used as placebo control as these cells are visually indistinguishable from DC and are considered immunologically inactive. Patients in both arms continued to receive monthly adjuvant temozolomide (150-200 mg/m2/day x 5 days every 28 days).

Treatment

Each DCVax-L treatment involved a dose of 2.5 million autologous tumor lysate-pulsed DCs administered intradermally (ID) in the upper arm, alternating arms between injection visits. MGMT (O6-methylguanine-DNA methyltransferase) gene promoter was methylated in 39.6% (n=131) and unmethylated in 48.9% (n=162), with information not available for 11.5% of patients (n=38). Because of the cross-over trail design, nearly 90% of the ITT population received DCVax-L.

Results

Treatment outcomes ITT population
At the time of analysis, 108 out of 331 patients (32.6%) were still alive. The median OS of the overall ITT population (n=331) was 23.1 months from the time of surgery, with 2- and 3-year survival rates of 46.2% and 25.4% respectively.

Long tail among ITT population
With immune-based therapies, a key focus is on the tail of the survival curve. Among the ITT patients with a surgery date ≥ 30 months prior to data collection (n=223), 30% (n=67) have lived ≥30 months and their KM-derived median OS estimate is 46.5 months. For patients with surgerydate ≥36 months (n=182), 24.2% (n=44) have lived ≥36 months and their KM-derived median OS is 88.2 months.

MGMT status
In patients with methylated MGMT (n=131) median OS was 34.7 months from surgery, with 2year survival of 66.7% and 46.4% for 3-year survival rates. In patients with unmethylated MGMT (n=162) median OS was 19.8 months for surgery, with 2- and 3- year survival rates of 32.1% and 11.0%, respectively.

Safety and toxicity
The most common adverse event was lymphopenia, occurring in approximately 170 patients (51%). The DCVax-L treatment was well tolerated, with only 7 ITT patients (2.1%) experiencing serious (Grades 3-4) adverse events that were deemed related or possibly related to the DCVax- L treatment. These included cerebral edema in 3 patients (0.9%), seizures in 2 patients (0.6%), nausea in 1 patient (0.3%) and lymph gland infection in 1 patient (0.3%).

Conclusion

The addition of DCVax-L autologous dendritic cell vaccine to SOC is feasible and safe. Collectively, the blinded interim survival data suggest that the patients in this Phase 3 trial are living longer than expected.

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Scientific article publishing date	29/05/2018
Identifier	BSC21_016EN

Category: Studies