About

Jessica Lang, PhD, is an Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison. She is also a faculty member at the Center for Precision Medicine and an affiliate faculty member at the Center for Genomic Science Innovation. Jessica obtained her bachelor's degree in Genetics in 2009 and her doctorate in Cancer Biology in 2014, both from the University of Wisconsin-Madison. Following her doctoral studies, she completed two postdoctoral fellowships at Arizona State University and The Translational Genomics Research Institute (TGen). In 2019, she was awarded an NCI K99/R00 grant to focus her research on the role of super-enhancers in high-grade serous ovarian carcinomas. Jessica joined the University of Wisconsin-Madison faculty in 2021, where she applies her expertise in translational biology, genomics, and epigenetics to advance her research. Outside of her professional work, Jessica enjoys spending time with her family, cooking, outdoor activities, reading, and game nights.

Research topics

• Medicine
• Computer Science
• Internal medicine
• Oncology
• Nanotechnology
• Materials science
• Gastroenterology
• Gynecology
• Biology
• Intensive care medicine
• Genetics
• Cancer research
• Pathology

Selected publications

• Prostate Cancer-Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future in a Chip

  International Journal of Molecular Sciences · 2026-02-05 · 1 citations

  articleOpen accessSenior authorCorresponding

  Cancer-associated fibroblasts (CAFs) are key regulators of the prostate tumor microenvironment (TME) with influence on disease progression and therapeutic response. CAFs originate from multiple precursors and retain remarkable plasticity while tumors evolve. Therefore, the CAF pool displays considerable functional heterogeneity, which is well-reflected in complex molecular signatures. However, overlapping biomarker patterns with other stromal subsets make it challenging to identify and assess the role of specific CAF subpopulations. Through reciprocal tumor-stroma interactions, CAFs promote extracellular matrix (ECM) remodeling, angiogenesis, metabolic reprogramming, and immune evasion, collectively fostering an adaptive niche that supports tumor survival, though some CAF subsets have been shown to support anti-tumor response. In prostate cancer (PCa), CAFs promote resistance to androgen receptor pathway inhibitor therapy, chemotherapy, and radiotherapy, emphasizing their potential value as therapeutic targets. However, CAF targeting has shown limited clinical benefit in PCa, due to complex, context-dependent CAF functions that make it challenging to exploit this unique stromal population for therapeutic gain. Recent advances in organ-on-a-chip (OOC) models offer new opportunities to investigate the mechanisms behind TME interactions and evaluate CAF-targeted strategies in physiologically relevant fully humanized environments. This review provides current insights into CAF heterogeneity and therapy resistance in PCa and highlights emerging translational OOC models to guide the development of more effective therapies to disrupt the TME.

  PublisherOA PDFDOI

• Abstract CT149: A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis

  Cancer Research · 2026-04-17

  article

  Abstract Background: Advanced metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with limited treatment options. Cabozantinib is a multi-tyrosine kinase inhibitor targeting VEGFR, MET, and AXL that has demonstrated activity in mCRPC patients, particularly those with bone and liver metastases. Based on our preclinical studies showing cabozantinib-mediated activation of innate immunity in PC, we investigated the efficacy of cabozantinib plus nivolumab in mCRPC patients (NCT05502315). Methods: This prospective, multi-center, single-arm, two-stage open-label phase II study enrolled patients with progressive mCRPC per PCWG3 criteria and prior androgen receptor pathway inhibitor exposure. Prior taxane was permitted. Patients received cabozantinib 40 mg daily orally plus nivolumab 480 mg IV every 4 weeks. The primary endpoint was radiographic progression-free survival (rPFS) at 6 months by RECIST 1.1/PCWG3. A Simon two-stage MiniMax design was used with 80% power, hypothesizing 6-month rPFS >30%. Stage 1 required ≥7 of 24 patients to be progression-free at 6 months to continue to Stage 2, which will enroll an additional 23 patients. Results: Twenty-four patients were enrolled in Stage 1 (median age 71 years). 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. Eight patients remained progression-free at 6 months, meeting continuation criteria for Stage 2. Median rPFS was 5.5 months (95% CI >3.6 months). Objective response rate was 17.6% (3/17 evaluable patients). Median baseline PSA was 28.05 ng/mL and median time to PSA progression was 1.87 (95% CI 1.81-3.78) months. One patient experienced PSA50. Grade ≥3 treatment-related adverse events occurred in 52% (n=12) of patients, with 5 treatment-related serious adverse events. Most common adverse events were anorexia 58% (n=14), diarrhea 58% (n=14), fatigue 54% (n=13), nausea 46% (n=11), anemia 38% (n=9), AST increase 38% (n=9), ALT increase 33% (n=8), constipation 33% (n=8), and hypothyroidism 29% (n=7). Conclusions: 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. Citation Format: Justine Panian, Lin Liu, Minya Pu, Emily Pittman, Samuel Pena, Archana Ajmera, Yu-Wei Chen, Christos Kyriakopoulos, Qian Qin, James Michael Randall, Tian Zhang, Joshua Michael Lang, Akash Patnaik, Rana R. McKay. A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT149.

  PublisherDOI

• A phase II study of lutetium-177 DOTATATE in metastatic prostate cancer with neuroendocrine differentiation.

  Journal of Clinical Oncology · 2026-03-01

  article

  TPS292 Background: Neuroendocrine differentiated prostate cancer (NED PCa) is an aggressive form of prostate cancer with few treatment options and a poor prognosis. There is evidence that NED PCa and advanced castration resistant prostate cancers (CRPC) overexpress the somatostatin receptor (SSTR), which can be targeted with Lu-177 DOTATATE, a radiopharmaceutical therapy that improves survival in neuroendocrine tumors of the midgut. We are conducting a phase II trials investigating Lu-177 DOTATATE in NED PCa. Methods: This is a phase II trial run through the National Cancer Institute’s (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN). Key inclusion criteria include evidence of neuroendocrine differentiation by histology (i.e. small cell carcinoma or positivity for synaptophysin or chromogranin A), molecular features (TP53, PTEN, and/ or RB1 loss), serum markers (chromogranin A or neuron-specific enolase), or clinical factors (progression of visceral metastases in the absence of PSA progression). Patients must have a positive Ga-68 DOTATATE PET/CT to proceed with Lu-177 DOTATATE therapy, defined as at least 1 lesion with a maximum standardized uptake value (SUV max ) greater than the mean SUV of normal liver. The primary objective for the trial is objective response rate (ORR), defined by Prostate Cancer Working Group 3 (PCWG3) criteria. Secondary objectives include 6-month radiographic progression-free survival as well as the correlation between ORR and change in fluorodeoxyglucose PET/CT signal pre- to mid-treatment. Exploratory objectives include SPECT/CT-based dosimetry of Lu-177 DOTATATE and gene expression analysis of circulating tumor cells collected prior to treatment, during treatment, and at time of progression. A pre-specified activity goal for the first 15 enrolled patients was met, and accrual of an additional 10 patients is currently in progress. Clinical trial information: NCT05691465 .

  PublisherDOI

• Matching Patients With Cell Surface–Targeted Clinical Trials Using Large Language Models

  JCO Precision Oncology · 2026-03-01

  articleOpen access

  PURPOSE: Cell surface-targeted therapies (CSTs) are a rapidly expanding class of cancer treatments with high specificity and reduced toxicity. Matching patients who express specific targets to CST clinical trials remains challenging because of complex eligibility criteria, diverse targets, and the absence of centralized, up-to-date trial databases. These gaps limit patient access and contribute to poor trial accrual. METHODS: We developed a large language model (LLM)-driven pipeline to identify and annotate CST clinical trials. Using a two-pronged approach, LLMs extracted target information from ClinicalTrials.gov and the National Cancer Institute Drug Database. Eight LLMs, including GPT-4o and several open-source models, were benchmarked against manually curated data sets of 814 CST trials and 814 non-CST trials. We evaluated model performance at target and trial levels and analyzed sources of error. We also provide an up-to-date database of open CST trials and their targets from the >100,000 total oncology clinical trials in ClinicalTrials.gov. RESULTS: GPT-4o achieved the highest accuracy in identifying CST trials (96.5%) and their targets (89.5%). Combining data sources improved performance, and accuracy increased with later trial phases. Most errors stemmed from vague therapy descriptions or string-matching issues. The model matched 94% of US trials and >95% of trials globally, with exceptions in China and New Zealand. In predicting cell surface localization, Gemma 3:27b and MedLlama3 correctly labeled all known clinical cell surface targets although performance varied beyond the most well-known CSTs. CONCLUSION: Our LLM-based approach enables real-time, automated matching of patients to CST clinical trials, addressing major barriers to enrollment and expanding trial accessibility. Errors were uncommon, and performance is poised to improve as LLMs evolve. Optimizing patient-trial matching for CSTs can improve both patient benefit and trial success.

  PublisherDOI

• Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4

  Journal of Clinical Oncology · 2026-02-26 · 5 citations

  articleOpen access

  PURPOSE: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. METHODS: We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS: PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION: PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

  PublisherOA PDFDOI

• A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis.

  Journal of Clinical Oncology · 2026-03-01

  article

  187 Background: Advanced metastatic castration-resistant prostate cancer (mCRPC) remains a largely lethal disease with limited treatment options. Cabozantinib is a tyrosine kinase inhibitor targeting VEGFR, MET, and AXL that has demonstrated activity in mCRPC patients, particularly those with bone and liver metastases. The CONTACT-02 trial showed efficacy of cabozantinib combined with the PD-L1 inhibitor atezolizumab in mCRPC. Building upon this background, we investigated the efficacy of cabozantinib plus nivolumab, a PD-1 inhibitor, in patients with mCRPC (NCT05502315). Methods: This prospective, multi-center, single-arm, two-stage open-label phase II study enrolled patients with progressive mCRPC per PCWG3 criteria and prior androgen receptor pathway inhibitor exposure. Prior taxane was permitted. Patients received cabozantinib 40 mg daily orally plus nivolumab 480 mg IV every 4 weeks. The primary endpoint was radiographic progression-free survival (rPFS) at 6 months by RECIST 1.1/PCWG3. A Simon two-stage MiniMax design was used with 80% power, hypothesizing 6-month rPFS >30%. Stage 1 required ≥7 of 24 patients to be progression-free at 6 months to continue to Stage 2, which will enroll an additional 23 patients. Results: Twenty-four patients were enrolled in Stage 1 (median age 71 years). 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. Eight patients remained progression-free at 6 months, meeting continuation criteria for Stage 2. Median rPFS was 5.5 months (95% CI >3.6 months). Objective response rate was 17.6% (3/17 evaluable patients). Median baseline PSA was 28.05 ng/mL and median time to PSA progression was 1.87 (95% CI 1.81-3.78) months. One patient experienced PSA 50 . Grade ≥3 treatment-related adverse events occurred in 52% (n=12) of patients, with 5 treatment-related serious adverse events. Most common adverse events were anorexia 58% (n=14), diarrhea 58% (n=14), fatigue 54% (n=13), nausea 46% (n=11), anemia 38% (n=9), AST increase 38% (n=9), ALT increase 33% (n=8), constipation 33% (n=8), and hypothyroidism 29% (n=7). Conclusions: 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. Clinical trial information: NCT05502315 .

  PublisherDOI

• Abstract B071: Monitoring the evolution of treatment resistance by transcriptional profiling of circulating tumor cells with RNAseq

  Cancer Research · 2026-01-20

  articleSenior author

  Abstract Background: Treatment with androgen receptor (AR)-targeted therapy, chemotherapy and 177Lu-PSMA-617 radioligand therapy have improved patient outcomes for patients with metastatic prostate cancer (PCa). However, development of treatment resistance remains universal, occurring through AR dependent mechanisms driving constitutive AR signaling, or lineage state transitions that bypass AR signaling and culminate in highly proliferative tumors, including those with luminal B (LumB) and neuroendocrine phenotypes. We recently described two distinct luminal phenotypes with high luminal and AR signaling gene expression but distinguished by high (LumB) or low (luminal A (LumA)) proliferation signature scores, with the LumB phenotype associated with shorter survival compared to the LumA phenotype. We also identified a low proliferation phenotype characterized by low AR/luminal signature and low proliferation, and a neuroendocrine phenotype characterized by high neuroendocrine and proliferation signature scores. Evolution of tumor biology has been difficult to monitor due to challenges in collecting serial tissue biopsies. Blood-based liquid biopsy is non-invasive and well suited for repeat sampling. RNA sequencing of circulating tumor cells (CTCs) provides an accessible means to perform longitudinal transcriptional profiling to track mechanisms of resistance over time. Methods: CTCs were isolated from patients with PCa during standard of care treatments including baseline and progression timepoints with automated microfluidic technology integrating negative and positive selection. CTCs and RNA were captured immunomagnetically. RNAseq data was assessed for CTC RNAseq phenotype, signature scores including CCP-31, signatures of tumor suppressor loss (p53, RB1, PTEN) and MYC signatures and genes previously identified as expressed in AR+ PCa or NEPC. Results: We analyzed longitudinal samples including 27 sets of matched baseline and post-treatment samples from 22 patients with metastatic PCa during treatment with AR targeted therapies, chemotherapy and 177Lu-PSMA-617. In 30% (8/27) of these patients, we observed a switch of CTC phenotype at treatment progression from pretreatment baseline sample. The most common switch (n=5) was from the LumA phenotype to LumB phenotype, which was associated with increased RB1 loss signature score (p=0.016). We observed a patient transitioning from a LumB phenotype to neuroendocrine at progression on 177Lu-PSMA-617 radioligand therapy. In this patient, coinciding with the phenotype shift, we detected decreased expression of KLK3 and FOLH1 (PSMA)and increased expression of ASCL1, INSM1 and SYP consistent with a shift from a luminal adenocarcinoma to a neuroendocrine phenotype. Conclusions: To better understand tumor evolution, it is essential to monitor molecular changes during treatment. RNAseq of CTCs enables longitudinal tracking of lineage phenotype transitions. Ongoing studies are investigating mechanisms that drive resistance and plasticity in larger, uniformly treated patient cohorts. Citation Format: Jamie M. Sperger, Marina N. Sharifi, Amy K. Taylor, Krisitin L. Rosche, David Gallo, Viridiana Carreno, Alex H. Chang, Emily Abella, Kaitlin Durnen, Muhammad Dar, Charlotte Linebarger, William M. Stump, Kendra Marr, Kyle T. Helzer, Grace C. Blitzer, John Floberg, David Kosoff, Rana R. McKay, Xiao X. Wei, Shuang G. Zhao, Joshua M. Lang. Monitoring the evolution of treatment resistance by transcriptional profiling of circulating tumor cells with RNAseq [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B071.

  PublisherDOI

• Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534

  Investigational New Drugs · 2026-03-03

  articleOpen access

  ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that combines AR antagonism and degradation via N-terminal domain binding, additionally targeting AR splice variants. In this study patients received ONCT-534 daily ranging from 40 to 1200 mg. The primary objectives were safety and dose-limiting toxicities (DLTs). Additional objectives included antitumor activity and AR signaling biomarkers. Adverse events (AEs) were assessed within the first 28 days for DLTs. Clinical activity was evaluated by PSA and radiographic progression per PCWG3 and RECIST v1.1. The trial was stopped early and not all patients were evaluated per protocol. Twenty-one patients received ONCT-534 across six doses. The most common AEs were anemia, back pain, and fatigue. While no DLTs were observed within 28 days, Grade 3/4 AEs occurred later in 9 patients (anemia most frequently). One patient discontinued due to treatment-related AE. No radiographic or PSA-based responses were observed; however, three patients showed PSA declines at week 4, with one achieving a PSA50 at time of study closure. Of 10 patients with baseline AR protein data, the median change was - 40.59% in AR protein levels at week 4. In the 300 mg cohort, 3 patients showed concordant decreases in AR protein and AR gene expression. Here, PSA levels correlated positively with AR target gene and AR gene expression. ONCT-534 had acceptable safety and demonstrated biological activity through AR protein degradation and AR signaling suppression in mCRPC patients. Although clinical responses weren't observed, these findings provide proof-of-concept for examining AR protein changes in patients receiving DAARIs.

  PublisherOA PDFDOI

• Abstract A031: Targeting prostate cancer bone metastasis with iNKT immunotherapy

  Cancer Research · 2026-01-20

  article

  Abstract Introduction: For men with metastatic castration resistant prostate cancer (mCRPC), there is an urgent need for improved therapeutics as the disease is highly lethal. Approximately 90% of mCRPC patients develop bone metastases. The bone tumor microenvironment (TME) is highly complex, involving dynamic interactions between tumor cells and bone-resident stromal populations that drive pathological remodeling, therapy resistance and create immunosuppression. Invariant natural killer T cells (iNKT cells) are a subset of “donor unrestricted” T cells that do not mediate alloreactivity and have strong potential as off-the-shelf immunotherapy agents. iNKT cells home to bone marrow and have been shown to modulate the bone TME in addition to directly killing tumor cells. To further investigate the mechanisms of iNKT modulation of the prostate cancer (PCa) bone TME, we used a microphysiological system (MPS), an advanced fully human 3D in vitro culture model that recreates the PCa bone microenvironment. Methods: The bone MPS includes 9 different primary cell types cultured in an optimized media formulation. The MPS comprises a main chamber filled with a collagen matrix containing osteoblasts, osteoclasts, adipocytes, mesenchymal stem cells, macrophages, fibroblasts, and PCa organoids, surrounding an engineered blood vessel mimic. iNKT cells were embedded within the bone stroma or added through the endothelial microvessel for trafficking readouts. MPS were analyzed using fluorescence microscopy to evaluate tumor cell viability (calcein-AM/ethidium homodimer), and trafficking of iNKT cells into the TME from the vasculature. Media was removed from the MPS for cytokine secretion analysis using multiplex bead-based ELISA and RNA was isolated from cells for gene expression analysis using qPCR. Results: We demonstrated that iNKT cells migrated into the bone TME from the vasculature, with migration increased in the presence of PCa tumor organoids. iNKT cells invaded into the tumor organoids and induced tumor cell death. Co-culture experiments demonstrated that this iNKT cell mediated tumor cell death was dependent on the presence of osteoclasts. qPCR revealed upregulation of FasL and chemokines CCL2, CCL4, CXCL9, and CXCL11 in the iNKT condition compared to control, suggesting activation of M1-type macrophages and induction of FasL-mediated cytotoxicity. Multiplex bead-based ELISA analysis showed upregulation of M-CSF, GM-CSF, G-CSF, IL-1α, TNFα, MIP-1α, IL-2, IL-9, MCP-3, and RANTES, consistent with enhanced pro-inflammatory reprogramming, and recruitment of effector immune cells. Conclusions: These findings suggest that iNKT cells are a promising immunotherapy for treatment of PCa bone metastases. In addition to killing tumor cells, iNKT cells can modulate the PCa bone metastatic niche which could contribute towards overcoming tumor-induced immunosuppression and promoting anti-tumor immunity. Citation Format: Cristina Sánchez-de-Diego, Nikhila S. Bharadwaj, Marcos Lares, Nikolett Lupsa, Erika Heninger, Joshua M. Lang, David J. Beebe, Jenny E. Gumperz, Sheena C. Kerr. Targeting prostate cancer bone metastasis with iNKT immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A031.

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• A multicohort phase 2 trial of androgen deprivation therapy (ADT), docetaxel (DOCE), and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumors and DNA damage repair (DDR) alterations.

  Journal of Clinical Oncology · 2026-03-01

  article

  183 Background: This multicenter phase 2 investigator-initiated trial evaluated ADT, DOCE, and NIVO in pts with de novo mHSPC. Cohorts were prospectively allocated by the presence of DDR alterations (C1), PD-L1 and CD8 positivity (C2), or absence of biomarkers (C3). Primary results from all cohorts are reported. Methods: Pts with newly diagnosed mHSPC (ECOG 0-2 and PSA >4.0ng/mL before ADT) were enrolled, allowing up to 140 days of prior ADT. Pts received continuous ADT, DOCE 75mg/m 2 and NIVO 360mg Q3W for 6 cycles, followed by NIVO 480mg Q4W for up to 2 years. Primary endpoint (PEP) was PSA < 0.2ng/mL at 7mo and considered promising if 2-sided 80% CI exceeded 20%. Secondary endpoints included PSA < 0.2ng/mL before next therapy, objective response rate (ORR), time to castration resistance (TTCRPC), overall survival (OS) and adverse events (AE). Planned enrollment was 60 pts (20/cohort). Biomarkers were centrally assessed. Results: 47 pts were enrolled between 5/2020-3/2024 (C1: 8, C2: 19, C3: 20). Due to evolving treatment landscape, abiraterone was permitted post-7mo in 1/2022, and enrollment was subsequently stopped early. Across cohorts, median age was 65y (IQR 60-72) and median PSA at ADT start 98ng/mL (IQR 36-477). 41 (87%) pts had high-volume metastases with 11 (23%) visceral disease. Median follow-up was 42mo. Pts received a median of 6 DOCE and 11 NIVO cycles. PSA < 0.2ng/mL at 7mo occurred in 3 (38%, 80% CI: 15%-66%) pts in C1, 3 (16%, 5.9%-32%) pts in C2, and 3 pts (15%, 5.6%-30%) in C3; 6 pts (2 in C2, 4 in C3) lacked data due to early discontinuation for AE or physician decision. Rate of PSA < 0.2ng/mL before next therapy was 4 (50%) in C1, 4 (21%) in C2, and 4 (20%) in C3. ORR was 0% (0/2) in C1, 50% (4/8) in C2, and 50% (6/12) in C3. Abiraterone was started by 11 (23%) pts on study, with median time from C1D1 of 11mo (range: 7-19). Survival outcomes are summarized in Table. Grade 3-4 treatment-related AEs occurred in 28 (60%) pts, most frequently neutropenia (30%) and leukopenia (11%). Conclusions: C2 and C3 did not meet the 7mo PSA response PEP, and C1 was underpowered for assessment. Pts with PD-L1 and/or CD8 high tumors tended to have longer TTCRPC and OS; however, the study was not designed for cross-cohort comparisons. Safety was consistent with individual profiles of each agent. With the expanding therapeutic arsenal for mHSPC, future studies should further explore biomarker-driven combination strategies to optimize treatment selection and pt outcomes. (NCT04126070). Clinical trial information: NCT04126070 . Cohort 1 (DDR altered, N=8) Cohort 2 (PD-L1/CD8 high, N=19) Cohort 3 (Biomarker negative, N=20) TTCRPC, median (95% CI) 8.8 (6.2-NR) 14.3 (5.3-38.6) 7.9 (5.1-NR) 3yr OS rate, % (95% CI)* 55 (14-83) 72 (46-87) 59 (33-78) *Median OS not reached in each cohort.

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Recent grants

• Cancer Center Administration

  NIH · $99.8M · 1997–2028

• Mechanisms of microenvironment mediated resistance to cancer cell surface targeted therapeutics

  NIH · $1.6M · 2020–2022

• Enhancing Epigenetic Analysis Of Rare Cells With Multi-Phase Microfluidics

  NIH · $3.1M · 2020–2026

• Validation of predictive liquid biomarkers for patients with metastatic prostate cancer

  NIH · $352k · 2021–2023

• VERSA: An Integrated, Multi-Endpoint Platform for Circulating Tumor Cell Analysis

  NIH · $1.6M · 2014–2020

Frequent coauthors

• Jamie M. Sperger

  University of Wisconsin–Madison

  194 shared

• Shuang G. Zhao

  University of Wisconsin–Madison

  158 shared

• David J. Beebe

  University of Wisconsin Carbone Cancer Center

  146 shared

• Erika Héninger

  117 shared

• David Kosoff

  University of Wisconsin–Madison

  96 shared

• Anupama Singh

  92 shared

• Charlotte N. Stahlfeld

  85 shared

• Jennifer L. Schehr

  University of Wisconsin–Madison

  83 shared

Labs

• Lang LabPI

  Translational Ovarian Cancer Genomics and Epigenetics Lab at University of Wisconsin-Madison