The final results of a phase 1/2 study of a therapy in recurrent glioblastoma multiforme (GBM) have been reported by Australian-based Telix Pharmaceuticals Ltd.
The therapy, TLX101 (4-L-[ 131I] iodo-phenylalanine, or 131I-IPA) administered with external beam radiation therapy (EBRT) and the primary objective was to evaluate and test the safety and tolerability profile of the intravenous therapy during the trial called IPAX-1.
Secondary objectives were to determine optimal dosing, biodistribution and radiation absorption into the tumor, as well as assess preliminary efficacy through clinical and imaging-based assessment of tumor response.
Primary objective
Final data up to the completion of the post-study follow-up period confirms the study has met its primary objective, demonstrating the safety and tolerability profile of TLX101 at the dosing range tested.
The study also delivered encouraging preliminary efficacy data for further evaluation, demonstrating a median overall survival (OS) of 13 months from the initiation of treatment in the recurring setting, or 23 months from initial diagnosis.
Given that GBM has a median survival from initial diagnosis of 12-15 months, the overall survival improvement trend seen in this patient population, Telix Pharmaceuticals said this clearly warrants further evaluation in a larger patient population.
Further investigation
Colin Hayward, chief medical officer at Telix Pharmaceuticals, said, “We are pleased to report this final outcome, which will be submitted for publication. We can reconfirm that TLX101 has demonstrated safety and tolerability profile and encouraging early efficacy data. The median overall survival of 13 months from initial treatment in the recurrent second line setting reinforces the validity of further investigation and dose escalation of TLX101 in patients with GBM.
“Due to the aggressive nature of this cancer and limited treatment options, we are experiencing a high level of interest in the follow-on study that Telix is now undertaking in newly diagnosed patients, as a front-line therapy in combination with standard of care treatment. In parallel we will continue to study TLX101 in the recurrent setting.”
Recurrent GBM is a highly aggressive cancer that progresses rapidly, and for which there are few effective treatment options. TLX101 is a systemically administered targeted radiation therapy that targets L-type amino acid transporter 1 (LAT-1), which is typically over- expressed in GBM. TLX101 has been granted orphan drug designation in the U.S. and Europe.
IPAX-1 results summary
Ten patients were enrolled of whom nine received the full study treatment dosing of ~2GBq (2000 MBq) of TLX101, either in the form of a single administration or one of two triple-fractionated regimens. The results demonstrated all dosing regimens, in combination with EBRT, were well tolerated.
Dosimetric analysis demonstrates that radiation exposure to key organs is well within acceptable safety limits.
The most frequent treatment emergent adverse events (TEAEs) were decreased lymphocyte count, fatigue, headache and hiccups, which occurred in three patients (30%), followed by decreased platelet count, diarrhea, cerebral oedema (swelling), and insomnia, which occurred in two patients (20%).
Well-tolerated therapy
Except for cerebral oedema, a typical side-effect of radiation to the brain, adverse events were of low grade, did not show any trends or patterns and were clinically manageable, with a significant proportion deemed unrelated to therapy. The therapy was generally well tolerated by patients.
Overall survival (OS) was a median of 13 months, from initiation of therapy in the recurrent disease setting.
Of the nine patients who received conventional imaging, four (44%) exhibited stable disease at day 135 and two (22%) at day 180, determined by longitudinal imaging.
Two patients remain alive at the time of study report.
Relapsed patients
Josef Pichler, principal investigator in the IPAX-1 study said: “When you consider that GBM has a median survival from initial diagnosis of 12-15 months, the potential benefit demonstrated in relapsed patients, in a second-line setting is encouraging.
“We are very motivated to continue to investigate TLX101 in a larger patient population in the planned phase II IPAX-L (Linz) study underway at Kepler University Hospital, with the goal of collecting additional safety and efficacy data for TLX101 in in combination with EBRT in patients with relapsed-glioblastoma.”
About Telix Pharmaceuticals
Telix Pharmaceuticals is a biopharma company focused on the development and commercialization of diagnostic and therapeutic products using Molecularly Targeted Radiation (MTR). Telix Pharmaceuticals is headquartered in Melbourne, Australia, with international operations in Belgium, Japan, Switzerland, and the U.S.