Prostate Cancer
Telix’s prostate cancer portfolio targets PSMA (prostate-specific membrane antigen), a protein expressed on the surface of prostate cancer cells, which is low or absent on most normal healthy cells. PSMA has become a major breakthrough in prostate cancer diagnostics and the growing field of nuclear medicine.
Overview
A summary of historical data related to TLX591
Academic review of PSMA-targeting radiopharmaceuticals: Of the first developed PSMA-binding monoclonal antibodies, J591 displays the highest binding affinity, and humanized J591 demonstrates highest binding affinity in the liver with minimal uptake in the urinary tract and salivary glands with low toxicities
Therapy for Metastatic Castration-Resistant Prostate Cancer
Demonstrates benefit of fractionated administration of 177Lu-J591 including 1) PSA decrease, 2) overall survival, and 3) favorable toxicity profile.
Demonstrates 1) feasibility, 2) tolerability, and 3) preliminary efficacy of combination therapy (fractionated doses of 177Lu-J591 + chemotherapy)
Demonstrates 1) favourable safety profile with reversible, dose-dependent hematologic toxicity, 2) accurate tumor targeting, and 3) PSA responses
Demonstrates 1) favorable safety and tolerability profile of multiple 30 mCi/m2 doses, and 2) targeting of PC metastases
Phase II ketoconazole, hydrocortisone, and J591 with 177Lu or 111In in nmCRPC: 177Lu-J591 with keto/HC leads to improved 18-month metastases-free survival vs. 111In-J591
ARPIs & PSMA Expression
Enzalutamide effect on PSMA-low prostate cancer: Enzalutamide induces PSMA expression in preclinical and clinical setting, augmenting tumor uptake of 68Ga-PSMA-11; thus, patients with low baseline PSMA levels who are pre-treatment with enzalutamide may therefore become eligible for 177Lu-PSMA therapy
Measurement of androgen receptor signaling with PSMA PET: Cell surface PSMA expression is androgen receptor dependent and can be quantitatively assessed by PET in prostate cancer xenograft models
Phase 1 docetaxel plus 177Lu-PSMA: The combination of 177Lu-J591 delivered as a single fractionated cycle with docetaxel/prednisone is feasible in patients with mCRPC and appears to have significant anti-tumor activity as measured by PSA and measurable disease response
Functional specificity for tumour-expressed PSMA
Review of PSMA-based imaging: J591 has shown potential as an imaging agent to predict changes in androgen receptor signaling after AR-targeted therapeutics
89Zr-J591 for ImmunoPET: 89Zr-J591immunoPET results in high tumor-to-background tissue contrast, and can be used to delineate and quantify PSMA-positive prostate tumors
Additional Resources
ProstACT SELECT Study of TLX591 Interim Readout
ProstACT GLOBAL
ProstACT SELECT
ProstACT TARGET
Intermediate to High Risk Localized and Suspected Metastatic Prostate Cancer
Demonstrates diagnostic accuracy including for low disease burden (Gleason score 6 or 7) for initial staging.
Demonstrates higher reproducibility and accuracy of PSMA vs conventional imaging
Demonstrates 1) high accuracy, even for detecting low burden disease (prostate-specific antigen levels ≥ 0.1 ng/mL); 2) reproducibility, and 3) safety for use in patients with biochemical recurrence
Demonstrates 1) accurate staging and 2) clinical utility and implications for treatment plans
Clinical Utility – Change in Patient
Demonstrates the utility of 68Ga-PSMA-11 PET for management decision-making in metastatic prostate cancer
Demonstrates the role of PSMA PET in risk stratification of patient selection for active surveillance and targeted biopsies
High detection rate in patients with very low PSA values: 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at low PSA levels (≤ 0.5 ng/mL)
Biopsy Guidance
Additive value of PSMA PET/CT to mpMRI for primary dx: For detection of clinically significant prostate cancer in patients with suspects PCa, the combination of MRI with PSMA PET results in a greater NPV than with MRI alone. Authors note that, “..it appears safe to further reduce required biopsy in men with negative PSMA and negative/equivocal MRI.”
Bone Lesions, Conventional Imaging, & Reproducibility
Demonstrates high rate of indeterminate bone lesions (IBLs) on 18F-DCFPyL PET/CT imaging, and highlights implications of incorrect interpretation of IBLs (e.g., unnecessary interventions) on patient quality of life
Demonstrates 1) significantly higher rate of undifferentiated bone uptake on 18F vs. 68Ga imaging, with an intraindividual comparison demonstrating > 8 times higher rate
Demonstrates 1) perfect inter-reader agreement for 68Ga-PSMA-11 scans, and 2) significantly lower inter-reader agreement for 18F-PSMA 1007 scans attributed to non-specific bone uptake
Demonstrates sensitivity of PSMA PET over 1) mpMRI for detection of extra-prostatic extension and 2) bone scans for bone staging
Demonstrates that “PSMA PET/CT reliably identifies bone metastases in CRPC patients, opening the door for bone-targeted therapies and potentially improving treatment sequences.”
Demonstrates PSMA PET has higher accuracy than bone scans and CT imaging for staging of patients with prostate cancer
Supports that “Interpretation of bone lesions is more challenging with 18F-labelled compounds [18F]F-PSMA-1007 and [18F]F-rhPSMA-7.3 compared to [68 Ga]Ga-PSMA-11”
Patient Selection for Directed Therapies; Safety & Tolerability
Demonstrates 1) utility of 68Ga-PSMA-11 PET for patient selection of PSMA-targeted therapy, and 2) safety and tolerability of 68Ga-PSMA-11 “cold kit”
Demonstrates utility of <sup>68</sup>Ga-PSMA-11 for RLT patient selection and prognostic value of PSMA parameters
Clinical Utility Across All Patient Paradigms and Journey
Surgical planning
Shows first DROP-IN β-probe to be successfully validated on ex vivo samples of prostate tumors with [68Ga]Ga-PSMA-11 imaging
Demonstrates PSMA-PET imaging can improve surgical guidance in men with ≥4+3 prostate cancer resulting in preservation of nerve-bundles
Demonstrates 1) detection of sentinel lymph nodes and 2) usability and performance for sentinel lymph node dissection
Response assessment
Radiotherapy guidance
Demonstrates PSMA PET can be a valuable tool for guiding SRT planning directed to the prostate bed in postoperative BCR or BCP
Prognostic indicator, survival
Demonstrates utility of PSMA imaging score as prognostic factor for survival
Additional resources
Kidney Cancer
Telix’s kidney cancer portfolio targets CAIX (carbonic anhydrase IX), an antigen expressed on the surface of clear cell renal cell carcinoma (ccRCC), the most common and aggressive form of kidney cancer, as well as a number of other solid tumours.
CAIX Overview
CAIX in cancer and its radiation responsiveness: CAIX plays many important roles in driving cancer cell growth and metastasis, is sensitive to radiation, and is almost exclusively expressed in cancer, suggesting CAIX could be an ideal therapeutic target
CAIX and acid transport in cancer review: CAIX plays a fundamental role in tumor metabolism and pH regulation, which drives cancer migration and metastasis; thus, CAIX inhibitors as well as inhibitors of the metabolic complexes that CAIX transports may be promising targets for cancer therapy
CAIX in renal cell carcinoma, review: CAIX is a promising target for diagnosis, prognosis, treatment monitoring, and therapy for patients with RCC
177Lu-girentuximab therapy, ccRCC
177Lu-girentuximab in advanced ccRCC: Treatment with 177Lu-girentuximab results in disease stabilization in over 50% of patients with progressive ccRCC and has a favorable tolerability profile
Phase 2, 177Lu-girentuximab in advanced ccRCC: 177Lu-girentuximab therapy has a favorable tolerability profile and is efficacious, with majority of treated patients experiencing disease stabilization.
Phase I, 177Lu-girentuximab in advanced ccRCC: 177Lu-girentuximab in metastatic ccrCC patients has a favorable tolerability profile and may stabilize previously progressive metastatic ccrCC
CAIX targeting, ccRCC
CAIX in ccRCC prognosis, diagnosis, and therapy: The vast majority of primary and metastatic ccRCC lesions have high and homogeneous CAIX expression, and CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC
CAIX Targeting, Other Cancers
CAIX correlation with FOXP3+ T cell tumor infiltration in non-small-cell lung cancer: CAIX is strongly associated with FOXP3+ regulatory T cell abundance in the tumor environment of non-small-cell lung cancer; thus, patients could benefit from a combination of immunotherapy with pharmaceutical agents such as CAIX inhibitors.
Targeted alpha therapy, RCC
CAIX-targeted alpha radionuclide therapy with 225Ac (225Ac-hG250): 225Ac-hG250 significantly prolongs survival in RCC mice model compared to untreated controls
Additional Resources
ZiPUP – TLX250
STARLITE-1
STARLITE-2
STARBURST
Diagnostic utility & Unmet Need
Demonstrates that TLX250CDx 1) has a favorable safety and tolerability profile, and 2) has high diagnostic performance for detection and characterization of clear-cell renal cell carcinoma in patients with renal masses (you can leave off the in patients part of you prefer).
CAIX Targeting, ccRCC
Demonstrates 1) diagnostic accuracy with significantly better sensitivity and specificity versus conventional imaging, and 2) high inter- and intra-reader agreement
Recent developments of CAIX-targeted PET/CT for ccRCC: 89Zr-girentuximab PET/CT can diagnose ccRCC in localized disease, differentiate ccRCC from non-ccRCC, and characterize metastatic disease burden
Diagnostic utility & Unmet Need
Review of novel renal mass imaging methods: Authors provide overview of methods including 89Zr-girentuximab PET/CT, molecular imaging, multiparametric MRI, 99mTc-sestamibi SPECT. Authors also note the superior signal-to-noise ratio achieved with 89Zr vs. 124I-radiolabelled girentuximab PET/CT imaging results
Safety & Tolerability; Dosimetry
Demonstrates 1) favorable safety profile, 2) diagnostic accuracy, and 3) similar dosimetry to other 89Zr-based PET tracers
Diagnostic Utility / Unmet Need
Demonstrates 1) superior diagnostic accuracy and 2) clinical utility and implications for patient management
Confirms 1) high diagnostic accuracy for differentiation and characterization of ccRCC, even for small lesions 2) high interreader reliability, and 3) favorable safety and tolerability profile
Highlights unmet need for accurate, non-invasive diagnosis, differentiation, and characterization of ccRCC and other renal lesions for better patient selection for surgical vs. conservative treatment
Highlights unmet need and associated economic burden for patients with Von Hippel-Lindau Disease-associated renal cell carcinoma
Additional Resources
High diagnostic performance of 89Zr-girentuximab PET, ZIRCON: For all evaluable patients, positive and negative predictive values were ≥91.7% and ≥73.7%, respectively
Optimal SUVmax, ZIRCON: For all evaluable patients, positive and negative predictive values were ≥91.7% and ≥73.7%, respectively, and accuracy >85.6%. The optimal SUVmax threshold to distinguish the ccRCC from other lesions was ≥24.1, based on Youden index. PET+ ccRCC had higher mean CAIX expression compared with PET‑ ccRCC patients (p<0.05)
Detection of other tumor types, ZIRCON: Of 11 patients with positive results on 89Zr-girentuximab PET who were negative for ccRCC on central histopathology, 9 had papillary RCC, and 1 each had sarcoma and oncocytoma.
Metastatic lesion detection, ZIRCON: 25 patients had ≥1 extrarenal lesions detected on imaging, which were primarily localized in bone, liver, lung, adrenal glands, and lymph nodes, and were visualized by both conventional and PET imaging with high degree of correspondence
Accuracy to detect very small lesions and reader agreement, ZIRCON: Sensitivity and specificity in lesions ≤2 cm ranged from 90-100%. Inter- and intra-reader consistency was 91% and 100%, respectively
Glioblastoma (Brain Cancer)
Telix’s GBM program targets LAT-1 (L-type amino acid transporter 1) a membrane transport protein that is typically highly expressed in GBM. TLX101 is a novel approach that is readily able to pass through the blood-brain barrier, the normal protective barrier that prevents many potential drug candidates from entering the brain.
Treatment for Glioblastoma Multiforme
Demonstrates 1) favorable safety profile and tolerability in recurrent GBM and 2) promising response to therapy
Demonstrates 1) favorable safety profile and tolerability. and 2) promising response to therapy
Systemic endoradiotherapy with 131I-IPA in refractory high-grade glioma: Systemic endoradiotherapy using 131I-IPA is not associated with clinically detectable toxicity and results in measurable anti-tumor effects
131I-IPA with external beam photon irradiation in malignant glioma: Systemic radionuclide therapy with 131I-IPA combined with external beam radiotherapy significantly prolongs median survival times and is more effective than any monotherapy alone in glioblastoma rat models
Additional Resources
IPAX-2
Diagnostic Accuracy & Clinical Utility
Glioma
Demonstrates high clinical value of amino acid PET, including 18F-FET PET, for identifying pseudo progression. TBRmax and TBRmean are reliable parameters.
Brain Metastases
Demonstrates high sensitivity and specificity of amino acid PET, including 18F-FET PET, for differentiation post-radiotherapy treatment-related changes from brain metastasis
Both Gliomas and Brain Metastases
Demonstrates clinical utility of hybrid 18F-FET PET/MRI for differentiation of disease progression from treatment-relayed changes
Demonstrates clinical utility of 18F-FET PET for differentiation of disease progression from treatment-relayed changes in both glioma and brain metastases setting
Rare Diseases and Bone Marrow Conditioning
The indications for bone marrow transplantation are increasing from hematological malignancies to more recently solid tumours and numerous autoimmune conditions. Traditional conditioning regimens are associated with morbidity and mortality from chemotherapy, limiting their use particularly in pediatric and rare diseases.
Experience
AL-amyloidoisis
Demonstrate 1) favorable safety profile, and 2) potential utility as sole conditioning agent prior to ASCT in AL-Amyloidosis
Experience by Condition, Chronic Granulomatous Disease
90Y-CD66 radioimmunotherapy, chronic granulomatous disease: authors report a survival rate of 75% at mean follow-up time of 53 months
Experience by condition, relapsed/refract active leukemia
90Y-CD66 radioimmunotherapy, children with relapsed/refractory acute leukemia, Phase 1: 90Y-CD66 RIT has a favorable safety and tolerability profile
Hematopoietic stem-cell transplant overview
Hematopoietic stem-cell transplantation review: While HSCT is a critical treatment for certain hematological malignancies, patients who undergo HSCT are subject to risk of significant toxicities, especially following the conditioning regimen.
Experience by Condition, Malignant and Nonmalignant Diseases
90Y-CD66 radioimmuntherapy, children with malignant and nonmalignant diseases: Treatment of pediatric and adolescent patients with 90Y-CD66 as conditioning before hematopoietic stem cell transplantation has a favorable toxicity profile and can achieve myeloablation when used in combination with standard or reduced-intensity conditioning
Experience by Condition, AL-amyloidosis
90Y-CD66 conditioning for autologous stem cell transplantation in systemic AL-amyloidosis: Treatment of AL-amyloidosis with 90Y-CD66 as a conditioning agent prior to autologous stem cell transplantation shows favorable safety and toxicity data up to day 100 post-transplant
Radiolabeling Optimisation
90Y radiolabeling optimizing with anti-CD66: Modification of 90Y-CD66 with a DTPA-based chelating agent shows excellent stability, purity, and CD66 radioimmunoreactivity and conditioning in patients prior to hematopoietic cell transplantation has a favorable tolerability profile
Pre-clinical Proof of Concept
Demonstrates 1) favorable pre-clinical characteristics, and 2) first-in-human use
Diagnostic Performance and Safety
Osteomyelitis
99mTc-besilesomab for diagnosis of osteomyelitis: 99mTc-besilesomab has a favorable safety profile, and is accurate and efficacious (with a higher sensitivity than 99mTc-HMPAO-labelled white blood cells) for the diagnosis of peripheral bone infections
Infective Endocarditis
99mTc-besilesomab SPECT/CT. infective endocarditis: 99mTc-besilesomab SPECT/CT is 86-100% sensitive and 100% specific for diagnosis of infective endocarditis
Telix’s lead imaging product, gallium-68 (68Ga) gozetotide injection (also known as 68Ga PSMA-11 and marketed under the brand name Illuccix®), has been approved by the U.S. Food and Drug Administration (FDA), by the Australian Therapeutic Goods Administration (TGA), and by Health Canada. No other Telix product has received a marketing authorisation in any jurisdiction. Pixclara and Zircaix brand names are subject to final regulatory approval.