NCT02766699

A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent GBM

A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of EGFR (Vectibix® Sequence)-Targeted EnGeneIC Dream Vectors Containing Doxorubicin (EGFR(V)-EDV-Dox) in Subjects With Recurrent Glioblastoma Multiforme (GBM)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Engeneic Pty Limited · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the Cerebral EDV study is to determine the safety and tolerability of EGFR(V)-EDV-Dox in order to establish the best dose level to be used in future studies. The study will also examine the body's immune response to EGFR(V)-EDV-Dox and assess if it is effective in the treatment of patients with recurrent glioblastoma multiforme (GBM).

Detailed description

This is an open-label, Phase 1, dose exploration and preliminary immunogenicity study of single agent EGFR(V)-EDV-Dox in subjects with recurrent glioblastoma (GBM). Eligible subjects enrolled in the study will receive EGFR(V)-EDV-Dox administered weekly for 7 weeks via IV 20 minute infusion, followed by radiological evaluation at week 8 (1 Cycle). Subjects may continue to receive subsequent cycles of EGFR(V)-EDV-Dox unless the subject becomes intolerant to investigational product (IP), withdraw consent or the individual is no longer receiving clinical benefit (factors taken in to consideration will be disease progression radiologically or clinically, and clinical benefits to quality of life). Tumour assessment will be repeated after each 7 week cycle (week 8). The study will take place in two parts, Part 1 (Dose Exploration) and Part 2 (Dose Expansion). Part 1 - Dose Exploration will assess the safety and tolerability of multiple doses of drug at two dose levels (5 x 10\^9 and 8 x 10\^9) and will enroll prior to Part 2. Three subjects will be recruited per dose level. Enrollment will begin with the 5 x 10\^9 dose level, and the decision to enroll to the 8 x 10\^9 dose level will follow a comprehensive safety evaluation and a standard 3 + 3 dose escalation study design. Part 2 - Dose Expansion will be conducted pending safety results of Part 1 to provide guidance regarding the recommended phase 2 dose (RP2D). Subjects will be treated and assessed as outlined in Part 1 above. If 0 out of 3 subjects, or 1 out of 6 subjects, experience dose limiting toxicities (DLTs) at the 5 x 10\^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. Similarly, if 0 out of 3 subjects, or 1 out of 6 subjects, experience DLTs at the 8 x 10\^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. If both dose levels are tolerated, a total of 10 subjects per dose level will be enrolled. A safety follow-up visit must be performed 30 (+5) days after the last dose of drug for all subjects.All subjects who discontinue investigational product and who have not withdrawn full consent to participate in the study will continue in the long term follow-up phase. Long term follow-up will continue approximately every 1 month for 12 months, from the 30 (+5) day follow-up visit, then approximately every 2-3 months for the extent of subject survival.

Conditions

• Glioblastoma
• Astrocytoma, Grade IV

Interventions

Type	Name	Description
DRUG	EGFR(V)-EDV-Dox	EGFR(V)-EDV-Dox using EnGeneIC EDV™ technology is a bacterially derived minicell which packages a toxic payload, Doxorubicin, into a 400 nm particle which targets specific cancer cells using bispecific antibodies (BsAb). BsAb-targeted, payload-packaged EDV nanocells only exit the leaky blood vessels associated with tumors and enter into the tumor microenvironment. The BsAb binds to the tumor cell-surface receptor, where the EDV is taken up, broken down within the cancer cell and releases the Doxorubicin. The residual EDVs that do not make it into the tumor microenvironment, are engulfed by cells of the immune system and since the EDVs are derived from bacteria, they carry potent immuno-stimulating components which appear to bypass the immuno-suppression caused by the tumor.

Timeline

• Start date: 2016-10-25
• Primary completion: 2021-08-21
• Completion: 2022-03-30
• First posted: 2016-05-10
• Last updated: 2025-06-03

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study