Spago Nanomedical utvecklar Tumorad, en nästa generations nanopartikelbaserad radiofarmaceutisk behandling avsedd att leverera målinriktad intern strålterapi till solida tumörer. Den pågående first-in-human-studien genomförs i Australien vid Cancer Research SA i Adelaide och St Vincent’s Hospital i Melbourne, där säkerhet, dosimetri och tidiga effektparametrar utvärderas.
Synligt tumörupptag – en klinisk milstolpe
Den senaste granskningen från DMC innebär ett viktigt bevis på Spagos Tumorad-plattforms potential. SPECT-avbildning har visat synligt upptag av ¹⁷⁷Lu-SN201 i tumörer, bland annat hos en patient med den sällsynta cancerdiagnosen adenoid cystisk karcinom (ACC), vilket stödjer läkemedelskandidatens föreslagna verkningsmekanism och kliniska potential.
DMC konstaterade även att den maximalt tolererade dosen (MTD) ännu inte har uppnåtts och rekommenderade därför en doseskalering till 20 MBq/kg. Hittills har 12 patienter med 10 olika tumörtyper behandlats, och säkerhetsprofilen bedöms som hanterbar, med främst övergående trombocytminskningar som är typiska för radiofarmaceutisk behandling.
Spago Nanomedical ser detta som en betydande framgång, eftersom bibehållen säkerhet är avgörande inom strålterapi. Bolaget betraktar sin säkerhetsprofil som en viktig konkurrensfördel jämfört med andra RNT-läkemedel, som ofta är förknippade med mer komplexa biverkningar.
Lägger grunden för fas IIa
Fas I-delen av Tumorad-01-studien syftar till att identifiera en optimal terapeutisk dos innan man går vidare till fas IIa-delen, där utvalda patientgrupper kommer att utvärderas för tidiga effektindikatorer.
Resultaten hittills kan betraktas som klinisk validering av Tumorads mekanism för effektiv leverans av strålning till humana tumörer och kan, enligt bolaget, öppna dörren för särläkemedelsstatus inom ACC. Det växande globala intresset för radiofarmaceutiska terapier stärker ytterligare Spagos strategiska position.
Studien bidrar även till att förfina dosimetri- och avbildningsmetoder, som bekräftar överensstämmelse med prekliniska data och stödjer precisionen i leveransen av lutetium-177. Denna konsekvens stärker förtroendet för Spagos nanopartikelbaserade tillvägagångssätt och dess potential mot flera tumörtyper.
Vd kommenterar
BioStock talade med Mats Hansen, vd för Spago Nanomedical, om nästa steg för ¹⁷⁷Lu-SN201 efter DMC:s granskning och rekommendation.
What does the confirmed tumor uptake of ¹⁷⁷Lu-SN201 mean for the program’s clinical credibility?
– This a very important milestone for the program as well as for the company. The fact that we now see clear uptake of ¹⁷⁷Lu-SN201 in human tumors, including in a patient with adenoid cystic carcinoma (ACC), shows that our platform delivery mechanism works as intended. This is the first real Proof-of-Concept in humans for Tumorad, and together with the good safety results so far, this strengthens the clinical credibility of the entire program.
How do the DMC’s latest findings – including dose escalation and Proof-of-Concept – influence your development priorities going forward?
– The DMC’s recommendation to increase the dose to 20 MBq/kg gives us the opportunity to further explore dosing with the aim of identifying MTD and supporting dosing for the next phase. The significant visible tumor uptake provides additional confidence in the determination of a therapeutic dose level. Overall, the new findings provide strong support for continued development of Tumorad. We are now preparing for the next phase of development, focusing on cancer types that show strong tumor uptake and exploring opportunities for orphan drug designation.
– Recruitment in Australia is going well, which helps us move efficiently toward the next DMC review, and eventually the Phase IIa part of the trial.
How does Tumorad’s safety profile compare with other lutetium-based radiotherapies in development?
– So far, the observed Tumorad safety is supportive of a dose increase. DMC’s analysis of data from all patients treated in the study confirms the previously demonstrated safety profile – that safety is manageable and consistent across all patients. We’ve seen a relatively homogeneous and expected profile, with effects mainly on blood platelets, and no signs of adverse effects on other critical organs, such as the kidneys, which can be an issue with some other lutetium-based therapies. While it’s early to compare directly, these results are encouraging and support the Tumorad platform.
What are the strategic advantages of the Tumorad delivery system in radiopharmaceutical therapy?
– Tumorad represent a unique approach for delivery of well-known medical isotopes emitting clinically effective radiation to tumors within the body. Our optimised carrier nanoparticles loaded with the well-known medical isotope lutetium-177 takes advantage of the frequent leakiness in blood vessels surrounding tumors to accumulate in the tumor tissue, a phenomenon known as the enhanced permeability and retention (EPR) effect. This physiological feature differentiates healthy tissue from cancer tissue and allows local delivery of an adapted radiation dose sufficient to treat the tumors while minimizing undesirable effects on surrounding tissue.
– In addition, it could allow for simultaneous treatment of several types of solid soft tissue tumors and metastases. Compared to external beam radiation, radiopharmaceutical therapy also enables irradiation of tumors that could not otherwise be treated, such as deeper situated tumors or tumors adjacent to vital organs.
Given that ACC is a rare cancer, could orphan drug designation support your development path?
– Yes, with significant visible tumor uptake of 177Lu-SN201 shown in a rare indication like ACC there is a clear rational to continue exploring opportunities with potential for orphan drug designation (ODD). An ODD offers several advantages, such as regulatory guidance, fee reductions, and market exclusivity once the drug is approved. A rare cancer type like ACC could also enable smaller, faster studies and make the project more attractive for partnerships. Overall, an orphan drug designation would help us move forward more efficiently while addressing a real unmet medical need.
How are Australian clinicians and patients responding to the trial so far?
– The response from both investigators and patients has been very positive throughout the trial. Our clinical sites at the two hospitals, Cancer Research SA in Adelaide and St Vincent’s Hospital in Melbourne, remain active and recruitment has progressed well. Myself and our CDO, Paul Hargreaves, will visit our designated CRO and the clinical teams at the end of October to secure the continued engagement for the study and progress preparations for the next step. Overall, I’m very proud and encouraged of the strong interest and confidence we see from both the clinical teams and participants.
What new insights are emerging from the ongoing dosimetry and imaging work?
– The purpose of the phase I/IIa Tumorad-01 study is to evaluate the safety, tolerability, dosimetry, and initial efficacy of 177Lu-SN201. Besides assessing safety, the primary goal of the phase I part of the study is to identify a possible therapeutic dose for further testing in selected patient groups in the phase IIa part of the study. The imaging data reported to date provides evidence that ¹⁷⁷Lu-SN201 accumulates in tumors as intended, and as we move to higher doses, we are getting more detailed information about how the drug distributes in the body. These insights will help us determine the optimal dose and set up for the next study phase.
What key results do you expect to achieve over the next six months?
– Our main focus is to further progress the Tumorad-01 study to achieve the main aim of identifying the MTD and establishing the dose level for phase IIa. Right now this means we look forward to inclusion of the first patient to the escalated dose cohort at 20 MBq/kg. In parallel, we explore potential development paths for Tumorad including the opportunities in indications with potential for orphan drug designation (ODD).
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