Pluvicto (lutetium Lu 177 vipivotide tetraxetan) / Novartis, Otsuka - LARVOL DELTA

End-to-end in vitro and in vivo evaluation of radiopharmaceuticals in patient-derived models (AACR 2026) - "Both in vitro and in vivo findings demonstrate distinct responses to [^177Lu]Lu-PSMA-617 treatment, consistent with varying PSMA expression levels, evidenced by diagnostic PET imaging and comprehensive PDX models characterization.Conclusions Our results highlight the importance of integrating radiochemistry expertise with clinically relevant patient-derived models to thoroughly characterize novel radiopharmaceuticals. This holistic approach enhances the predictive accuracy of preclinical studies and ensures that emerging therapeutic strategies are closely aligned with clinical demand."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Comparative evaluation of 225Ac-PSMA-Trillium with other 225Ac-PSMA-SMOL assets in a preclinical prostate cancer xenograft model (AACR 2026) - P1 | "Here, we compared 225Ac-PSMA-Trillium with three other 225Ac-PSMA-SMOLs, i.e., 225Ac-PSMA-617, 225Ac-PSMA-R2 and 225Ac-PSMA-I&T, which all utilize a DOTA chelator for complexing 225Ac...177Lu-PSMA-617 SPECT imaging was performed to evaluate tumor uptake...In summary, 225Ac-PSMA-Trillium showed the highest tumor uptake and the strongest tumor growth inhibition with a clear dose response compared with the other 225Ac-PSMA-SMOLs. These data support the clinical development of 225Ac-PSMA-Trillium (NCT06217822)."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

²²⁵Ac-RAX104: A novel PSMA-targeted radioligand optimized for actinium-225 demonstrates enhanced tumor retention and superior efficacy (AACR 2026) - "Although the clinical success of ¹⁷⁷Lu-PSMA-617 (Pluvicto) has established PSMA-targeted radioligand therapy (RLT) as an effective treatment for metastatic castration-resistant prostate cancer (mCRPC), emerging clinical evidence indicates that ²²⁵Ac-based RLT can deliver even greater therapeutic efficacy owing to the high linear energy transfer of α-particles and the radionuclide's 9.92-day physical half-life. Collectively, these results demonstrate that ²²⁵Ac-RAX104 achieves optimal kinetic alignment with ²²⁵Ac's physical decay and biological action, delivering enhanced tumor exposure and potent therapeutic efficacy at one-fifth the dose of ²²⁵Ac-PSMA-617. These findings support ²²⁵Ac-RAX104 as a promising next-generation PSMA α-radioligand therapy with the potential to improve outcomes in mCRPC and warrant further clinical development."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Development and evaluation of a novel high affinity PSMA-targeted radioligand177Lu-PSMA-3D1015 for prostate cancer (AACR 2026) - "Background: The clinical efficacy of PSMA targeted RLT for metastatic PCa has been well established by Pluvicto®. 177Lu-PSMA-3D1015 exhibits high PSMA affinity and prolonged retention in tumor, potentially driving potent efficacy at lower doses. Its distinct hepatobiliary excretion profile differentiates it from existing therapies. These findings address key limitations of current RLTs, and further clinical trials are ongoing."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Advanced preclinical cancer models and imaging protocols for translational treatment studies in orthotopic prostate, bladder, liver, pancreatic and brain cancer (AACR 2026) - "Tumor growth was monitored using bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and ultrasound (US), while SPECT/CT imaging was applied for target engagement of [¹⁷⁷Lu]Lu-PSMA-617... We successfully developed complex surgical procedures for establishing orthotopic models and models of metastatic spread for cancers with an unmet clinical need. All models presented with key characteristics of human disease. Combined with multimodal, reliable and state-of-the-art imaging readouts, this is an attractive platform to increase the translational value of preclinical studies with novel anti-cancer therapies and combinations."

Metastases • Preclinical • Bladder Cancer • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

First target disclosure for the preclinical development of ATNM-400, a first-in-class actinium-225 radioconjugate with pan-tumor efficacy in solid tumors (AACR 2026) - "In vivo, ATNM-400 demonstrated sustained tumor uptake with off-target exposure in normal tissues, driving potent anti-tumor activity in:• Prostate cancer: ATNM-400 outperformed androgen receptor (AR) pathway inhibitor enzalutamide, 177Lu-PSMA-617, and 225Ac-PSMA-617, producing durable regressions and complete responses in enzalutamide- and 225Ac-PSMA-617-resistant models.• EGFR-mutant lung cancer: ATNM-400 synergized with EGFR inhibitor osimertinib, achieving complete cures in animals, correlating with increased target expression in osimertinib-resistant models.• Breast cancer: ATNM-400 exhibited tumor regressions in HR+ breast cancer, TNBC and combination activity in estrogen receptor (ER) inhibitor tamoxifen- and HER2 antibody trastuzumab-resistant tumors, correlating with increased target expression. ATNM-400 exhibits robust pan-tumor activity, overcomes resistance to AR, EGFR, and HER2/ER-targeted therapies, and demonstrates a favorable safety profile. These..."

Pan tumor • Preclinical • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

Preclinical evaluation of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in mice bearing castration-resistant prostate adenocarcinoma patient-derived xenografts (AACR 2026) - "Further studies are warranted to optimize dosing strategies and evaluate long-term safety. Importantly, this work underscores the critical role of PDX models in capturing real receptor expression and tumor heterogeneity, thereby enhancing the translational relevance of radiopharmaceuticals in preclinical development."

Preclinical • Castration-Resistant Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer

Synergistic integration of nanobodies and a specialized linker library: A novel radionuclide drug conjugate (RDC) platform paving the way for next-generation radiotherapeutics with optimal druggability and therapeutic index (AACR 2026) - "By leveraging GQ's nanobody-based RDC platform, a potential best-in-class anti-PSMA RDC has been developed that demonstrates a comprehensively superior profile to Pluvicto®—including optimized half-life, enhanced tumor uptake, excellent safety, and potent efficacy in CDX models and mCRPC patients—thereby establishing a transformative paradigm that expands the promise of nanobody-based therapeutics beyond existing modalities to novel tumor targets."

First-in-human • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Preclinical characterization and evaluation of JSB462 (Luxdegalutamide), a novel AR degrader, and its combinations in prostate cancer (AACR 2026) - P2 | "JSB462 demonstrates potent AR degradation at sub-nanomolar concentrations in vitro and dose-dependent tumor growth inhibition in mouse xenograft models, including those resistant to enzalutamide and with high levels of AR. Here, we show preclinical combination data of JSB462 with abiraterone and Pluvicto® that support further investigation of these regimens. Towards that end, two phase 2 trials of JSB462 in combination with abiraterone in patients with high-volume mHSPC (NCT06991556) as well as in combination with Pluvicto® in patients with mCRPC (NCT07047118) are ongoing."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • CRBN • CYP17A1

Mapping PSMA-617 sensitivity in prostate cancer PDX models to enable combination therapy and resistance studies (AACR 2026) - "As proof-of-concept, PARP inhibition with olaparib was evaluated as a radiosensitizer in ST1273/RTR. Tumor relapse occurred 29 days post-[¹⁷⁷Lu]Lu-PSMA-617 monotherapy, whereas combination treatment extended relapse to 49 days, demonstrating enhanced antitumor efficacy. Collectively, these fully characterized prostate PDX models-validated for PSMA expression and [¹⁷⁷Lu]Lu-PSMA-617 responsiveness-integrated with comprehensive clinical data, establish a robust, translationally relevant platform for preclinical evaluation of innovative combinatorial strategies in RLT."

Combination therapy • IO biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Monitoring of Disease in Patients Receiving 177LU-PSMA-617 Therapy in Routine Practice. (PubMed, Clin Genitourin Cancer) - "There was marked heterogeneity in the use of imaging for disease monitoring during LuPSMA therapy 10% of patients experienced radiographic disease progression in the absence of PSA progression. PSA alone may be insufficient as a marker of disease response, and radiographic assessment remains an important part of disease monitoring in patients receiving LuPSMA."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A peptide-based drug delivery system to target metastatic prostate cancer (AACR 2026) - "Lately, therapeutic agents that selectively target PCs such as [177Lu]Lu-PSMA-617 have shown promise, suggesting that tumor-specific drug delivery may greatly improve the management of metastatic castration-resistant PC...These results suggest that the MHP1 peptide may serve as a promising platform to target metastatic PC. Characterization of the receptor may also lead to additional PC-specific therapies and deeper understanding of PC biology."

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Next-generation liquid biopsy for circulating tumor cell detection in metastatic prostate cancer (AACR 2026) - "We further extended this workflow to a clinical study evaluating treatment-associated changes in abundance of CTC expressed with different PCa biomarkers, PSMA, STEAP1, and STEAP2 in patients receiving Pluvicto therapy...Early results indicate that STEAP-family markers remain detectable in patients with low or fluctuating PSMA expression, supporting their value in monitoring therapeutic response. Together, these findings position STEAP1, STEAP2 and PSMA as robust biomarkers for next-generation CTC-based liquid biopsy assays and demonstrate their potential to enhance diagnostic sensitivity and treatment monitoring in mPCa."

Biopsy • Circulating tumor cells • Liquid biopsy • Metastases • Tumor cell • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • EPCAM • FOLH1 • PTPRC • STEAP1 • STEAP2

Development of novel syngeneic mouse models of mHSPC and mCRPC for evaluation of radiopharmaceuticals on the immune tumor microenvironment (TME) (AACR 2026) - "In vivo, we conducted biodistribution studies with 177Lu-PSMA-617 in mice bearing bilateral subcutaneous MyC-CaP and MyC-CaPPSMA+ tumors. 100% of MyC-CaPPSMA+ tumors treated with degarelix regressed for 20 days before rebounding.Conclusion Here we reveal translationally relevant models of mHSPC and mCRPC for mechanistic investigations of α- and β-emitting RPTs. Leveraging these tools, we aim to study DNA damage and immune responses to generate foundational data to guide the development of combination therapies to improve outcomes of RPT for patients with mHSPC and mCRPC."

Preclinical • Tumor microenvironment • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • HER-2

Multi-omic single-cell assessment of castration-resistant prostate cancer patients receiving177Lu-PSMA-617 and pembrolizumab shows timing of radioligand therapy alters immune response (AACR 2026) - P1 | "Our study demonstrates the critical importance of treatment sequencing to fully harness the immunomodulatory potential of RLT using a single dose of 177Lu-PSMA and optimize synergy with PD-1 blockade in mCRPC. While initiating with either 177Lu-PSMA or concurrently starting 177Lu-PSMA with pembrolizumab resulted in an increase in DCs, starting with pembrolizumab first resulted in lower frequencies T cells and DCs suggesting that this schedule could be detrimental to immune outcomes."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8

Prostate cancer phenotypes determined from circulating tumor DNA associate with outcomes to 177Lu-PSMA-617 therapy (AACR 2026) - "Abstract is embargoed at this time."

Circulating tumor DNA • Late-breaking abstract • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Randomized phase 2 trial of flexible and extended dosing of 177Lu-PSMA-617 molecular radioligand therapy (FLEX-MRT): 2025 Study Protocol Update (PSMA 2026) - No abstract available

Clinical • P2 data • Oncology

SPPADE symptom burden and ePRO-based outcome prediction in patients with mCRPC treated with 177Lu-PSMA-617 (LuPSMA) (PSMA 2026) - No abstract available

Clinical • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Prospective study to evaluate usefulness of Fluciclovine F 18 in predicting clinical outcome in patients undergoing radioligand therapy with 177Lu-PSMA-617 (PSMA 2026) - No abstract available

Clinical • Clinical data • Oncology

An Assessment of Time Toxicity in Patients Receiving [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer (mCRPC) (PSMA 2026) - No abstract available

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Global pharmacovigilance insights into [¹⁷⁷Lu]Lu-PSMA-617: a disproportionality-based safety signal detection approach using VigiBase (PSMA 2026) - No abstract available

Adverse events • Clinical • Oncology

The predictive role of SPECT/CT semiquantitative parameters at the first RLT cycle with [177Lu]Lu-PSMA-617 in advanced mCRPC: a preliminary lesion-based analysis (PSMA 2026) - No abstract available

Metastases • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

PSMA+ extracellular vesicles (EVs) and circulating tumor DNA (ctDNA) reveal potential biomarkers of response to 177Lu-PSMA-617 (PSMA 2026) - No abstract available

Biomarker • Circulating tumor DNA • Oncology

Interpreting Clonal Hematopoiesis Following [177Lu]Lu-PSMA-617: Clinical Risk Versus Genomic Signal. (PubMed, J Nucl Med) - No abstract available

Journal • Hematological Disorders

A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis. (ASCO-GU 2026) - P2 | "The CONTACT-02 trial showed efficacy of cabozantinib combined with the PD-L1 inhibitor atezolizumab in mCRPC...Baseline characteristics: 50% (12/24) had de novo metastatic disease, 91.7% (n=22) had bone metastases, 29.2% (n=7) bone-only disease, 16.7% (n=4) visceral metastases, 66.7% (n=16) received prior chemotherapy, and 25% (n=6) prior ¹⁷⁷Lu-PSMA-617 therapy... The CANOPY trial met its interim efficacy threshold, demonstrating activity of cabozantinib plus nivolumab in mCRPC patients. The combination showed manageable toxicity. The study continues to Stage 2 enrollment to further evaluate this promising combination therapy."

Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AXL