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The 2026 PSMA & Beyond Conference
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Targeting the Cell Surface
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| Modalities for Targeting the Cell Surface
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| Evan Yu, MD
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| At the PSMA & Beyond 2026 conference, Evan Yu highlighted multiple emerging prostate cancer cell-surface targets (beyond PSMA) and emphasized that effective therapies depend on factors like target biology, drug design, and tumor heterogeneity. He reviewed key therapeutic modalities—including radioligand therapy, antibody-drug conjugates, bispecific antibodies, and CAR-T—each with distinct strengths, tradeoffs, and resistance mechanisms.
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| ADCs and BiTEs and Their Role in Prostate Cancer
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| Tanya B. Dorff, MD
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| Tanya Dorff highlighted that both antibody-drug conjugates (ADCs) and bispecific T-cell engagers (BiTEs) show promising activity in metastatic prostate cancer, with emerging targets like CD46, B7H3, STEAP1, and hk2 potentially outperforming PSMA in some settings. Clinical data demonstrate meaningful PSA and tumor responses, though toxicities—especially cytokine release syndrome with BiTEs—remain a key challenge.
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| DLL3: Does Target Expression Determine the Method of Targeting?
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| Rahul Aggarwal, MD
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| Rahul Aggarwal highlighted that DLL3 is a key target in neuroendocrine prostate cancer, with its level and pattern of expression helping determine the most effective therapeutic approach (e.g., ADCs, T-cell engagers, or radioligand therapy). He showed that T-cell engagers and radioligand therapies may work even in heterogeneous or lower-expression settings, while ADCs typically require higher target density and have faced toxicity challenges.
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| PSMA PET in Prostate Cancer Drug Development: Regulatory Challenges and Considerations
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| William Maguire, MD
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| William Maguire emphasized that while PSMA PET is widely used in clinical practice, it creates major regulatory challenges in prostate cancer trials due to unclear, less-validated endpoints and variability in how it influences patient selection and treatment decisions. He noted that conventional imaging endpoints (e.g., radiographic progression-free survival) remain essential for drug approvals, as PSMA PET-based measures are not yet fully validated or clearly clinically meaningful.
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| Incorporating PSMA PETs in Registrational Trials
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| Alicia Morgans, MD, MPH
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| Alicia Morgans highlighted how PSMA PET can be effectively incorporated into registrational trials, using the ARASTEP study as a model, where PSMA PET–based progression-free survival serves as the primary endpoint alongside conventional imaging as a key secondary measure. She emphasized that rigorous trial design— including blinded central imaging review, standardized scan timing, and multiple supporting endpoints— is essential to ensure reliability and regulatory acceptance.
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Landscape of Clinical Trials
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| Review of Phase 1/2 Compounds Recently Published
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| Jeremie Calais, MD, PhD
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| Jeremie Calais reviewed the phase 1/2 radiotheranostic landscape as of March 2026, identifying ~75 investigational agents targeting PSMA and emerging non-PSMA pathways with human data. Notable PSMA innovations include next-generation ligands such as 67Cu-SAR-Bis-PSMA, 177Lu-Ludotadipep, and 225Ac-PSMA-Trillium, alongside novel isotopes showing promising early activity in mCRPC. Expanding targets beyond PSMA—such as FAP, SSTR, CAIX, GRPR, and STEAP1—highlight a rapidly evolving pipeline across GU and other solid tumors.
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| Scaling Operations in Theranostics Clinical Research - Integrating Teams, Processes, and Regulatory Strategy
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| Stephanie Lira
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| Stephanie Lira outlined UCLA Theranostics' growth from 10 members in 2019 to a multidisciplinary team by 2026, driving trial expansion post-68Ga-PSMA-11/Pluvicto approvals and the 2024 Center opening, with surging complexity via oncology/urology collaborations. Core strategies include tailored regulatory workflows, CICare patient engagement, cross-functional alignment, and a 6-9 month trial launch process from design to accrual, overcoming hurdles like scanner/staff limits via dedicated slots, outsourcing, and staggering appointments.
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Developing Novel Radioligands
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| Does FAP Have a Future: Pro
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| Wolfgang Fendler, MD
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| Wolfgang Fendler argued for FAP's theranostic future, highlighting its high expression in sarcoma/GI tumors as an ideal stromal target, with [68Ga]Ga-FAPI-46 PET showing 90% PPV for FAP+ tumors in a 2025 ph2 trial. 90Y-FAPI-46 RLT achieved 48% DCR in 30 sarcoma patients, while emerging 161Tb-FAPI dimer optimizes dosimetry vs 90Y. Next-gen ligands like 177Lu-PNT3090, FAMI-mFS, 177Lu-OncoFAP-23, and 177Lu-/225Ac-RTX2358 enhance targeting, positioning FAP for disease stabilization/regression.
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| Does FAP Have a Future: Con
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| Lena Unterrainer, MD
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| Lena Unterrainer argued against FAP's theranostic viability due to poor tumor retention, low absorbed doses vs approved agents like PSMA/DOTATATE, and lack of curative potential. Basket trials across heterogeneous entities/isotopes yield vast variability, entity-dependent/heterogeneous expression, and variable uptake, complicating evidence without a "clinical workhorse" scenario. Safety risks include 38% gr3/4 events; combos remain unproven amid "trial-and-error" isotope/disease matching and missing prospective data.
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