Rindopepimut Plus Bevacizumab Shows Prolonged Survival in Recurrent Glioblastoma

David Reardon, MD

The vaccine rindopepimut (CDX110) plus bevacizumab induced tumor regression in a subset of patients with recurrent glioblastoma, according to David Reardon, MD, clinical director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, at the Society for Neuro-Oncology’s (SNO’s) Annual Meeting in Miami Beach, Florida.

Reporting on the phase II results from the ongoing ReACT study, Reardon, the current president of SNO, said use of the vaccine and bevacizumab can induce “potent EGFRvIII-specific immune response” in patients who are naïve or refractory to bevacizumab.

The findings show promise for both progression-free survival (PFS) and overall survival (OS) for patients with the EGFRvIII mutation. “Growing data links EGFR expression to poor long-term survival,” Reardon said.

Rindopepimut has a unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), according to the study abstract. It is delivered intradermally with granulocyte macrophage colony-stimulating factor. In addition to rindopepimut, the use of bevacizumab has the potential to augment EGFRvIII-specific immune response and antitumor activity by inhibiting vascular endothelial growth factor (VEGF) and its immunosuppressive properties, according to Reardon.

To be included in the study, patients were required to have a histological diagnosis of glioblastoma, have an EGFRvIII+ tumor, have relapsed glioblastoma; and have had previous treatment with surgery, conventional radiation therapy, and temozolomide.

A group of 72 patients who were bevacizumab-naïve (Group 1) were randomized 1:1 to receive bevacizumab along with a double-blinded injection of rindopepimut or KLH (the latter of which was used as the control). These patients also had not received any other VEGF inhibitors previously.

A second group of patients who were bevacizumab-refractory (Group 2/2C) received bevacizumab along with open-label rindopepimut. These patients had progression during or within 2 months of receiving bevacizumab. This group started as 25 patients but continues to expand.

The primary endpoint is a 6-month PFS rate and evaluation of antitumor activity related to rindopepimut. Researchers are also analyzing safety, tolerability, and EGFRvIII-specific immune response.

In Group 1, there was a 27% PFS at 6 months for those receiving both the vaccine and bevacizumab compared with an 11% PFS at 6 months for those receiving the control agent and bevacizumab (P = .048). Of the 72 patients treated, 12 continue to receive treatment, and 30 are still tracked for survival. OS was improved by 53% with rindopepimut. The median was 12 months with the vaccine versus 8.8 months for single-agent bevacizumab (P = .0208).

The objective response rate in Group 1 for the vaccine and bevacizumab group compared with the control and bevacizumab using RANO criteria was 23% compared with 12%.

In the initial Group 2/2C cohort, all patients completed treatment, and 2 patients continue to be tracked for survival. “There was evidence of rare but prominent antitumor activity,” Reardon said. The expanded cohort of 28 additional patients for Group 2/2C have all completed treatment, and 11 patients are currently being tracked for survival.

Additionally, 2 other patients in Group 2/2C had prestudy progression more than 2 months after using bevacizumab. This patient maintained a complete response for about 11 months, and the second patient had an unconfirmed complete response, according to the study abstract.

There was a median peak rindopepimut-induced anti-EGFRvIII humoral response of 1:25,600. Prolonged OS was associated with rapid titer generation.

The most commonly reported adverse event was grade 1 to 2 injection-site reaction(s), along with grade 2 edema in a small percentage of patients, according to Reardon.

“The results show favorable potential for OS in the patients receiving rindopepimut,” Reardon said. “There was a survival benefit compared with bevacizumab alone.” Additionally, more patients who received rindopepimut were able to stop using steroids, Reardon added.

When interpreting the study data, Reardon encouraged attendees to consider that the results focus on patients who are EGFRvIII+, a subset that can be more challenging and the prognosis in these patients is poor.

Reardon D, Schuster J, Tran D, et al. ReACT: A phase II study of rindopepimut vaccine (CDX-110) plus bevacizumab in relapsed glioblastoma. Presented at the Society for Neuro-Oncology’s (SNO’s) annual meeting. Miami Beach, Florida, November 14, 2014. Abstract Number. IT-30

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