Clinical trial, phase 1/2 — German GLORIA trial (NCT04121455); US FDA orphan drug and Fast Track designations Source: Nature Communications 2024 and 2026 papers, ESMO 2024 presentation
One of the leading aptamer cancer drug trial results comes from Germany. In a phase 1/2 trial combining radiotherapy with olaptesed pegol (NOX-A12), an L-RNA aptamer that blocks CXCL12, a signalling molecule that helps cancer regrow, radiographic tumour responses were reported in 9 of 10 patients. In an expansion group that added bevacizumab, 5 of 6 patients (83.3%) had a tumour response and median overall survival was 19.9 months.
What is an aptamer cancer drug?
An aptamer is a “nucleic acid medicine”: a short single strand of DNA or RNA that folds into a three-dimensional shape and binds to a specific protein. Like an antibody it picks out its target, but it can be made by chemical synthesis. Aptamers are already a class of approved medicines. In December 2004 the US FDA approved pegaptanib, an eye-disease drug, as the first aptamer medicine, and in August 2023 the RNA aptamer avacincaptad pegol was approved to treat geographic atrophy. The terms are explained in Nucleic acid medicine and aptamers: start by separating the terms.
In cancer, a leading aptamer with human results published in journals is olaptesed pegol, developed by TME Pharma in Germany. It is made of L-RNA, the mirror image of natural RNA. The drug captures and blocks a signalling molecule called CXCL12, which stimulates blood vessel formation and is known to be used by tumours to regrow after radiotherapy. In other words, it was developed to help “protect” the effect of radiotherapy.
Which patients were in the GLORIA trial?
The GLORIA trial (NCT04121455) was run at six major neuro-oncology centres in Germany. It enrolled patients with newly diagnosed glioblastoma who still had tumour after surgery and whose MGMT gene promoter was not methylated. In these patients the standard chemotherapy drug temozolomide often works poorly, so new treatments are especially needed. Photodynamic therapy, another treatment used for brain tumours, is covered separately in Glioblastoma photodynamic therapy.
Patients received olaptesed pegol by weekly intravenous infusion together with radiotherapy (60 Gy). In the first stage the dose was raised through 200, 400 and 600 mg to check safety (10 patients); in the expansion stage, the anti-angiogenic drug bevacizumab (10 mg/kg every 2 weeks) was added to 600 mg (6 patients).
What results did the trial report?
| Treatment group | Patients | Reported results |
|---|---|---|
| Radiotherapy + olaptesed pegol (dose escalation) | 10 | 9 with radiographic tumour response, 4 partial remissions, median overall survival 389 days (12.7 months), 6-month progression-free survival 40.0% |
| Radiotherapy + olaptesed pegol + bevacizumab (expansion) | 6 | 1 complete and 4 partial responses (response rate 83.3%), median progression-free survival 9.1 months, median overall survival 19.9 months, 2 patients alive beyond 2 years |
Sources: Giordano FA et al., Nature Communications 2024 (dose escalation) / Giordano FA et al., Nature Communications 2026;17:3405 (expansion). Median overall survival in standard-of-care comparison cohorts with similar characteristics was 9.5 months (internal hospital data) and 11.0 months (external German data).
In the first stage, a tumour blood-flow measure (rCBV) also fell in 9 of 10 patients (90%), supporting the idea that the drug suppresses vessel regrowth in the tumour. The expansion results were presented orally at the 2024 European Society for Medical Oncology (ESMO) Congress and published in 2026; in a post hoc analysis, progression-free and overall survival with bevacizumab were significantly longer than with radiotherapy plus olaptesed pegol (p=0.009, p=0.021). The investigators said they had established “proof-of-principle” for blocking CXCL12 and the vessel growth factor VEGF together.
How common were side effects?
- In both stages there were no dose-limiting toxicities or treatment-related deaths; the maximum tolerated dose was not reached in the first stage, and 600 mg per week was set as the recommended phase 2 dose.
- In the expansion group there were no grade 4 or 5 adverse events, and only 2 of 139 adverse events (1.5%) were attributed to olaptesed pegol alone.
- The most common adverse event was hair loss (5 patients, up to grade 2), which was not classified as caused by olaptesed pegol. One grade 2 rise in a liver enzyme (ALT) was reported in the expansion group, so regular blood tests are used during treatment.
What stage is it at, and what comes next?
Olaptesed pegol is a drug in clinical trials that has not yet received marketing approval. The US FDA has granted orphan drug designation for glioblastoma to the radiotherapy combination, and in April 2024 granted Fast Track designation to the combination with radiotherapy and bevacizumab, for newly diagnosed glioblastoma with tumour remaining after surgery that does not respond well to chemotherapy. It also has orphan designation for glioma in Europe.
The FDA has also cleared an investigational new drug (IND) application for a phase 2 trial, and the investigators have proposed confirming the results in randomised trials against standard treatment. The drug is not approved in Japan, so for those interested, the realistic step is to discuss possible participation in overseas clinical trials with the treating team. Public information on nucleic acid medicine and aptamers in Japan is collected on our Nucleic Acid Medicine & Aptamer Information page.
What should I ask my doctor?
- What is the MGMT methylation result for my tumour, and which treatments are recommended because of it?
- How much tumour remains after surgery, and might I meet the conditions for a clinical trial?
- What records are needed to look for a trial that adds a new drug during radiotherapy?
- What should be checked when an anti-angiogenic drug such as bevacizumab is used?
Frequently asked questions
Have aptamer cancer drugs shown effects in people?
Yes. In the German GLORIA phase 1/2 trial, tumour responses were reported in 9 of 10 patients who received olaptesed pegol with radiotherapy, and in 5 of 6 patients when bevacizumab was added.
How is an aptamer different from an antibody drug?
Both bind selectively to a target, but an antibody is a protein made in cells, while an aptamer is a short nucleic acid made by chemical synthesis. Olaptesed pegol is made of L-RNA, a mirror-image structure.
Are there approved aptamer drugs?
Yes. The US FDA approved pegaptanib in 2004 and avacincaptad pegol in 2023. Both treat eye diseases, and clinical trials of aptamers in cancer are continuing.
Related: Nucleic acid medicine and aptamers: start by separating the terms · Glioblastoma Photodynamic Therapy in Japan: Insurance and Survival · CAR-NK vs CAR-T: Side Effects, Manufacturing and Approval Status
Sources
- Giordano FA, Layer JP, Leonardelli S et al. L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial. Nature Communications 2024;15. DOI 10.1038/s41467-024-48416-9
doi.org/10.1038/s41467-024-48416-9
Checked: 2026-10-18 - Giordano FA, Layer JP, Turiello R et al. L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy and bevacizumab in newly-diagnosed glioblastoma: expansion of the phase I/II GLORIA trial. Nature Communications 2026;17:3405. DOI 10.1038/s41467-026-71362-7
tmepharma.com/downloads/poster/Giordano2026.pdf
Checked: 2026-10-18 - Giordano FA et al. Dual inhibition of post-radiogenic angio-vasculogenesis in glioblastoma: results of the phase I/II GLORIA trial. ESMO Congress 2024, Abstract 445MO
oncologypro.esmo.org (ESMO 2024, 445MO)
Checked: 2026-10-18 - TME Pharma. US FDA Fast Track Designation for NOX-A12 in Brain Cancer (2024-04-02)
businesswire.com/news/home/20240402114902
Checked: 2026-10-18 - Ng EWM et al. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nature Reviews Drug Discovery 2006;5(2):123-132
doi.org/10.1038/nrd1955
Checked: 2026-10-18 - FDA Approves New Treatment for Geographic Atrophy (Izervay, avacincaptad pegol), AJMC 2023
ajmc.com/view/fda-approves-new-treatment-for-geographic-atrophy
Checked: 2026-10-18 - DrugBank. Avacincaptad pegol (RNA aptamer, complement C5 inhibitor)
go.drugbank.com/drugs/DB15165
Checked: 2026-10-18
Written by the FTH editorial team. Sources checked 2026-10-18 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
