Clinical Trials

Glioblastoma Treatment with Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients (GLORIA)
(ref: NCT04121455)
Status: active, not recruiting

Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive forms of brain cancer. Patients with this devastating orphan disease are faced with extremely poor prognosis and a staggering 95% of them will not survive beyond 5 years. The standard of care – a combination treatment, including surgery, radiotherapy and chemotherapy – unfortunately is not curative. Moreover, not all patients benefit clinically from chemotherapy, which thus provides limited efficacy while increasing side-effect burden on patients. There is a huge unmet need for an effective approach to treat GBM that prevents tumor recurrence. Our approach is built on research and data suggesting that tumor microenvironment (TME) plays a critical role in how effective anti-cancer therapies are at fighting the disease.

Our research has shown exceptionally promising results in particular for the NOX-A12 combination with an anti-vascular agent bevacizumab on top of radiotherapy. By inhibiting both pathways of blood vessel re-growth in the tumor, the clinical data have shown statistically significant improvement in survival, doubling of median overall survival (mOS 19.9 months), and deeper and more durable responses vs standard of care reference cohort (mOS 9.5 months).

GLORIA is Phase 1/2 study in glioblastoma (brain cancer) patients resistant to standard chemotherapy (unmethylated MGMT promoter) consisting of a dose-escalation part with NOX-A12 plus radiotherapy and an expansion arm combining NOX-A12 with radiotherapy plus bevacizumab (VEGF inhibitor).

Results in NOX-A12 + RT + anti-VEGF combination generated and reported to date from a 6-patient cohort^2,3:

Statistically significant improvement in survival vs NOX-A12 + RT (p=0.021) and vs SoC matched cohort (p=0.003)
Doubling of median overall survival: final mOS 19.9 months vs SoC mOS 9.5 months
100% of patients attained radiographic partial responses (PR) of the tumor lesions (>50% shrinkage).
83% of patients achieved durable (>6 months) partial responses by mRANO criteria (modified Response Assessment in Neuro-Oncology), which takes into account radiographic response as well as other factors such as clinical condition of the patient.
50% of patients achieved >99% tumor size reduction incl. 1 complete response where the tumor disappeared completely and was no longer detectable by MRI
All mRANO partial responders maintained stable neurologic function as assessed by the NANO (Neurologic Assessment in Neuro-Oncology). Other quality of life measurements were stable or improved in the majority of patients with a median follow-up of 7.9 months.
The triple combination of NOX-A12, radiotherapy and bevacizumab was well tolerated and safe. No dose-limiting toxicities were observed.

NOX-A12 regulatory designations:

Orphan Drug Designation for glioblastoma/glioma (FDA and EMA)
Fast Track Designation for glioblastoma (FDA)

Statistically significant improvement in survival in GBM for NOX-A12 + anti-VEGF + Radiotherapy presented at ESMO 2024

Therapies with NOX-A12 indicate promising and exciting efficacy, and potential for clinical benefit over standard of care.

Cohort Therapy	Patients with Tumor Size Reduction	Patients with Partial Response (>50% tumor reduction)
Standard of care historical control arm (n=20)¹	25%	10%
NOX-A12 + RT (n=10)¹	90%	40%
NOX-A12 + RT + anti-VEGF (n=6)²	100%	100% (83% mRANO)

1. Giordano (2022) ASCO Annual Meeting Presentation #2050 link
2. Giordano (2022) SNO Annual Meeting Poster Presentation #CTNI-67 link & TME Pharma Press Release 19 November 2022 link

3. TME Pharma Press Releases link
RT = Radiotherapy; Beva = bevacizumab. Standard of care = RT + chemotherapy