Abstract Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vascularization. The response to bevacizumab is transient and short-lived (4–6 months) after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to to determine the safety and effectiveness (over-all survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 16 recurrent bevacizumab-naïve GBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (39–74), 5 patients (31%) are female, and average KPS is 83 (70–100). Thirteen patients are deceased and were unblinded at the time of further progression: 5 received vaccine, 7 received placebo, and 1 is non-evaluable due to discontinuation before completing 1 cycle. Median overall survival of the deceased patients treated with ERC1671 + Bevacizumab was 328 days (10.9 months), compared to 245 days (8.2 months) for patients treated with Placebo + Bevacizumab. While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. The phase 2 randomized, double-blinded study is ongoing with the addition of 2 subsites.

Abstract ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to determine the safety and effectiveness (overall survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 22 recurrent bevacizumab-naïve rGBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (33–74), 7 patients (32%) are female, and average KPS is 82.3 (70–100). Of the 22, two discontinued before completing one cycle of therapy and two remain on blinded treatment. Currently 18 patients are unblinded due to further progression: 8 were on vaccine and 10 on placebo. Five of those on placebo crossed to vaccine at progression. All but one of the 18 are now deceased. Median overall survival of unblinded patients randomized to ERC1671 + Bevacizumab (n = 8) is 264.5 days from the start of study treatment, compared to 182 days for those randomized to placebo + Bevacizumab who did not cross over (n = 5). Median overall survival of unblinded patients on vaccine at randomization or crossover is 328 days after first study treatment (n = 13). While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. This phase 2 randomized, double-blinded study is ongoing, with the addition of one more site.

Abstract Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vasculature. The response to bevacizumab is transient and short-lived after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor cell lysates. The proposed action of ERC1671 is the stimulation of the patients’ immune system. This ongoing phase 2 study has a goal to determine the safety and effectiveness of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab for recurrent GBM. ERC1671/GM-CSF is intradermally administered 2-3 times a week and for five total into maximum 18 days, while cyclophosphamide is orally administered for 4 days at the beginning. GM-CSF dose is 250 µg/m2 and cyclophosphamide dose is 50 mg/day. Bevacizumab is administered as standard of care at 10 mg/kg every 2 weeks. The treatment cycle is 28 days. 9 recurrent bevacizumab-naïve GBM patients, with KPS higher than 70, were treated with ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab v. Placebo + Bevacizumab. Median age was 59 (48-74), with 2 patients being female, and the average KPS 80 (70-100). These patients were unblinded at the time of further progression – 4 received vaccine, 4 received placebo, and 1 was non-evaluable due to discontinuation prior to completion of 1 cycle. Overall survival of patients treated with ERC1671 + Bevacizumab was more than 513 days, compared to patients treated with Placebo + Bevacizumab was 213 days (p=0.048). First clinical results for toxicity show an equal distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs. The addition of ERC1671/GM-CSF/Cyclophosphamide to bevacizumab for recurrent glioblastoma resulted in a clinically meaningful survival benefit with minimal additional toxicity. The phase 2 randomized, double-blinded study is ongoing with anticipated 2 subsites.

Abstract ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to determine the safety and effectiveness (overall survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 22 recurrent bevacizumab-naïve rGBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (33–74), 7 patients (32%) are female, and average KPS is 82.3 (70–100). Of the 22, two discontinued before completing one cycle of therapy and two remain on blinded treatment. Currently 18 patients are unblinded due to further progression: 8 were on vaccine and 10 on placebo. Five of those on placebo crossed to vaccine at progression. All but one of the 18 are now deceased. Median overall survival of unblinded patients randomized to ERC1671 + Bevacizumab (n = 8) is 264.5 days from the start of study treatment, compared to 182 days for those randomized to placebo + Bevacizumab who did not cross over (n = 5). Median overall survival of unblinded patients on vaccine at randomization or crossover is 328 days after first study treatment (n = 13). While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. This phase 2 randomized, double-blinded study is ongoing, with the addition of one more site.

Abstract Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vascularization. The response to bevacizumab is transient and short-lived (4–6 months) after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to to determine the safety and effectiveness (over-all survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 16 recurrent bevacizumab-naïve GBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (39–74), 5 patients (31%) are female, and average KPS is 83 (70–100). Thirteen patients are deceased and were unblinded at the time of further progression: 5 received vaccine, 7 received placebo, and 1 is non-evaluable due to discontinuation before completing 1 cycle. Median overall survival of the deceased patients treated with ERC1671 + Bevacizumab was 328 days (10.9 months), compared to 245 days (8.2 months) for patients treated with Placebo + Bevacizumab. While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. The phase 2 randomized, double-blinded study is ongoing with the addition of 2 subsites.

Abstract

BACKGROUND

ERC1671 is an allogeneic/autologous therapeutic glioblastoma (GBM) vaccine composed of whole, inactivated tumor cells mixed with tumor cell lysates derived from the patient and three GBM donors. Previously published compassionate use data showed an overall survival (OS) of 43 weeks (10 months) in patients with a good performance status.

METHODS

In this double-blinded, randomized, phase 2 study bevacizumab-naïve patients with recurrent GBM were randomized after surgery to receive either ERC1671 in combination with GM-CSF and cyclophosphamide plus bevacizumab, or placebo plus bevacizumab. The trial is registered with ClinicalTrials.gov (NCT01903330). Interim

RESULTS

Nine patients, with a KPS 70, were randomized and treated. At the time of further progression, these patients were unblinded, as stipulated by the protocol, which revealed that four had received vaccine, four had received placebo, and one was non-evaluable. Median OS of patients treated with ERC1671 plus bevacizumab was 12 months, with one patient surviving >2 years. In the group treated with placebo plus bevacizumab, median OS was shorter at 7.5 months, with all patients having succumbed within 1 year. Toxicity analysis showed an equal distribution of adverse events (AE) between the vaccine and placebo groups, with no grade 4 or 5 toxicities. The maximal CD4+ T lymphocyte count in the peripheral blood correlated with OS in the ERC1671 but not in the placebo group.

CONCLUSIONS

The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a potential survival benefit with minimal additional toxicity. The maximal CD4+ T lymphocyte count in the peripheral blood correlated with OS. The study is ongoing with the addition of two other sites.

Aim

ERC1671 is an allogeneic/autologous therapeutic glioblastoma (GBM) vaccine - composed of whole, inactivated tumor cells mixed with tumor cell lysates derived from the patient and three GBM donors.

Methods

In this double-blinded, randomized, Phase II study bevacizumab-naive patients with recurrent GBM were randomized to receive either ERC1671 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) (Leukine^® or sargramostim) and cyclophosphamide plus bevacizumab, or placebo plus bevacizumab. Interim results: Median overall survival (OS) of patients treated with ERC1671 plus bevacizumab was 12 months. In the placebo plus bevacizumab group, median OS was 7.5 months. The maximal CD4⁺ T-lymphocyte count correlated with OS in the ERC1671 but not in the placebo group.

Conclusion

The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional toxicity.