Experts Spotlight Noteworthy GU Cancer Abstracts Ahead of the 2025 ASCO Annual Meeting

Pedro Barata, MD, MSc, FACP

As anticipation builds for the 2025 ASCO Annual Meeting, genitourinary (GU) oncology experts are closely tracking several key presentations that may influence future standards of care across prostate, bladder, and kidney cancers. In this preview article, leading clinicians in the GU space shared which abstracts they believe warrant attention due to their potential to shift practice, clarify current approaches, or affirm the utility of emerging biomarkers that may refine treatment selection.

Exclusive insights were shared by:

• Pedro Barata, MD, MSc, FACP, the director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center; the Miggo Family Chair in Cancer Research at University Hospitals; and an associate professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio
• Stephanie Berg, DO, a medical oncologist for the Lank Center of Genitourinary Oncology at Dana-Farber Cancer Institute; and an instructor in medicine at Harvard Medical School in Boston, Massachusetts
• Matthew Galsky, MD, a professor of medicine (hematology & medical oncology) at the Icahn School of Medicine at Mount Sinai; as well as the director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, and associate director for Translational Research at The Tisch Cancer Institute in New York, New York
• Yair Lotan, MD, a professor of urology, chief of Urologic Oncology, and holder of the Jane and John Justin Distinguished Chair in Urology at the University of Texas (UT) Southwestern Harold C. Simmons Comprehensive Cancer Center; as well as medical director of the Urology Clinic at UT Southwestern and Parkland Health and Hospital System in Dallas
• Katy Beckermann, MD, PhD, medical director of GU Clinical Research at Tennessee Oncology in Nashville.
• Bogdana Schmidt, MD, MPH, a urologic surgeon at the University of Utah in Salt Lake City
• Guru Sonpavde, MD, medical director of Genitourinary (GU) Oncology, assistant director of Clinical Research Unit, and Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute in Orlando, Florida
• Michael Serzan, MD, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute; and an instructor of medicine at Harvard Medical School
• Bicky Thapa, MD, MS, FACP, a physician instructor in medicine at Harvard Medical School

Read on to learn which presentations these experts have bookmarked and why such research could have meaningful implications for clinical practice.

​​Editor’s note: This preview will continue to be updated with additional abstracts to watch in GU oncology leading up to the 2025 ASCO Annual Meeting.

Kidney Cancer

Abstract 4506: Combination casdatifan plus cabozantinib expansion cohort of phase 1 ARC-20 study in previously treated patients with clear cell renal cell carcinoma.

Session time: Sunday, June 1, 9:45 AM-12:45 PM CDT

Michael Serzan, MD

Serzan: Casdatifan [AB521] is a novel HIF-2⍺ inhibitor that demonstrated overall response rates [(ORRs) of approximately] 25% to 33% and [greater than] grade 3 treatment-emergent adverse effects [(AEs) in approximately] 41% to 52% [of patients] across dose levels in phase 1 data presented at the [2025 Genitourinary Cancers Symposium (ASCO GU)]. It will be intriguing to see if targeting HIF-2⍺ and VEGF with casdatifan plus cabozantinib [Cabometyx] can improve ORR and durability of response, [although we should be] mindful of the potential added toxicity of the combination.

Barata: This abstract is reporting on a novel HIF-2⍺ inhibitor casdatifan [in combination] with the well-established TKI cabozantinib in patients with metastatic clear cell RCC (ccRCC). Novel combinations in RCC are needed, and this combination is moving forward into a phase 3 trial, so it will be important to take a look at preliminary data [with the agent] as the phase 3 study rolls out; [this agent may have the] potential to change practice in patients with previously treated metastatic RCC.

Abstract 4515: Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with previously untreated clear cell renal cell carcinoma (ccRCC): Results from an expansion cohort of the phase 1b STELLAR-002 study

Session time: Saturday, May 31, 1:15-2:45 PM CDT

Serzan: Triplet therapy is the next frontier that has the potential to improve outcomes for patients with metastatic ccRCC. Results from [the phase 3] COSMIC-313 study [NCT03937219] presented at the 2025 ASCO GU showed that cabozantinib plus ipilimumab [Yervoy] and nivolumab [Opdivo] improved progression-free survival [PFS]; however, [the combination] was associated with high rates of grade 3/4 treatment-related AEs relative to ipilimumab plus nivolumab [alone]. STELLAR-002 [NCT05176483] is investigating whether using zanzalintinib [XL092]—a novel VEGF TKI with a shorter half-life than cabozantinib—plus nivolumab and relatlimab-rmbw (Opdualag) holds promise as a triplet therapy for first-line metastatic ccRCC.

Abstract 4510: Genomic characterization of baseline and post-progression tumors in IMmotion010, a randomized, phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with high-risk localized renal cell carcinoma (RCC).

Session time: Saturday, May 31, 4:30-6:00 PM CDT

Serzan: Although the role of adjuvant anti-PD1 [therapy] with pembrolizumab [Keytruda] is established for patients with high-risk resected ccRCC, there is a paucity of understanding what mechanisms drive resistance to therapy. This genomic analysis of tumors at baseline and post-progression may guide the selection of which patients may benefit most [from] adjuvant anti-PD-1/-L1 therapy and lend insight into the optimal systemic regimen for patients who experience disease recurrence.

Abstract 4516: Ipilimumab and nivolumab in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated on the phase 3 PDIGREE (Alliance A031704) trial: Results from Step 1 analysis.

Session time: May 31, 1:15 PM – 2:45 PM CDT

Katy Beckermann, MD, PhD

Beckermann: PDIGREE is a randomized phase 3 clinical trial (NCT03793166) run through cooperative groups and presented by Tian Zhang, MD, MHS, of Harold C. Simmons Comprehensive Cancer Center, which will represent a significant advancement in frontline RCC using a novel adaptive clinical trial design. Patients received ipilimumab and nivolumab followed by adaptation of treatment based on response assessment. Patients with complete responses continued nivolumab monotherapy, those with progressive disease switched to cabozantinib monotherapy, and others were randomized to intensified treatment of nivolumab with cabozantinib vs nivolumab alone. Where we do not yet have definitive biomarkers, this idea of adaptive therapy could decrease financial toxicity and toxicities while maximizing efficacy and allowing for personalized treatment.

Prostate Cancer

LBA5006: Phase 3 AMPLITUDE trial: Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes.

Session time: Tuesday, June 3, 9:45 AM-12:45 PM CDT

Barata: This abstract is reporting on the first (of many) combination regimens that include a PARP inhibitor in patients with metastatic hormone-sensitive prostate cancer [mHSPC]. After the positive phase 3 trials with PARP inhibitors combined with androgen receptor pathways inhibitors—MAGNITUDE [NCT03748641], PROPEL [NCT03732820], and TALAPRO-2 [NCT03395197]—it will be important to know their efficacy in an earlier stage of the disease. [AMPLITUDE (NCT04497844)] has the potential to change practice.

Stephanie Berg, DO

Berg: This will be practice-changing for homologous recombination—deficient [HRD] mHSPC and pending subgroups, such as [those with] low- vs high-volume [disease, as well as] BRCA1/2, ATM, and other HRD mutations. [However], the primary end point is radiographic PFS; it is unlikely that we will see the overall survival benefit during this presentation.

Abstract 5007: A multicenter, randomized, phase 2, investigator-initiated ETCTN trial of olaparib + radium-223 vs. radium-223 in men with castration-resistant prostate cancer (CRPC) with bone metastases (BM) (COMRADE): Initial efficacy and biomarker analysis.

Session time: Tuesday, June 3, 9:45 AM-12:45 PM CDT

Barata: We’ve known that the combination of radium-223 with a PARP inhibitor is active, as demonstrated in other earlier studies. As radium-223 is emerging as a safe and active partner with other active systemic therapies, I [am] interested to know more about the signal emerging from this combination. With the expanded use of radioligand therapies and PARP inhibitors, this study’s findings could provide additional information about the further development of both therapies, which are not practice-changing yet.

TPS5113: Mevrometostat in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study.

Session time: June 2, 9:00 AM – 12:00 PM CDT

Bicky Thapa, MD, MS, FACP

Thapa: EZH2 is often expressed in patients with metastatic castration-resistant prostate cancer [mCRPC] and is linked to aggressive disease and treatment resistance. This study aims to shed light on the role of epigenetic inhibition, specifically EZH2 inhibition, and its potential synergy with androgen receptor [AR] blockade to combat resistance. It will be particularly interesting to see if subgroup analyses from this trial demonstrate a significant clinical benefit, especially in prostate cancer patients with chromatin remodeling gene mutations and HRD gene mutations.

Additionally, the results of a phase Ia/Ib study (NCT04846478) investigating the combination of talazoparib [Talzenna] and tazemetostat [Tazverik] in mCRPC, conducted by Atish Choudhury, MD, from Dana-Farber Cancer Institute in Boston, MA, will also be noteworthy.

Bladder Cancer

Abstract 4503: Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA.

Session time: Sunday, June 1, 9:45 AM-12:45 PM CDT

Berg: Using ctDNA in the adjuvant setting in a prospective manner is being studied in [the phase 2/3] A032103/MODERN study [NCT05987241] led by Dr Galsky, so to see it being used in a retrospective sense of clearance or positivity will be very intriguing [and may inform us on] how we can apply it to our current patients with MIBC using [the phase 3 NIAGARA (NCT03732677) regimen].

Beckermann: In March 2025, FDA approved the addition of perioperative durvalumab to chemotherapy based on HR of 0.68 for EFS and 0.75 HR for OS with an approximate 10% pCR increase seen in the NIAGARA trial for patients with stage II bladder cancer. At this year's ASCO Annual Meeting, Thomas Powles,MD, MBBS, MRCP, of Barts Cancer Center, will discuss ctDNA collected before and after neoadjuvant therapy and cystectomy to identify minimal residual disease and predict recurrence risk. This updated data to include ctDNA correlates and real-time monitoring could revolutionize risk stratification and guide future trial designs and clinical decisions.

Abstract 4502: Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

Session Time: Sunday, June 1, 9:45 AM-12:45 PM CDT

Matthew Galsky, MD

Galsky: [This study will result in] further characterization of features associated with response to enfortumab vedotin-ejfv (Padcev) with pembrolizumab, [which is] now a standard treatment for [patients with] metastatic urothelial cancer.

Abstract 4517: Sasanlimab in combination with bacillus Calmette-Guérin (BCG) in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): Event-free survival (EFS) subgroup analyses based on disease stage from the CREST study.

Session time: Saturday, May 31st, 1:15-2:45 PM CDT

Bogdana Schmidt, MD, MPH

Schmidt: I am looking forward to seeing the additional data from the [phase 3] CREST trial [NCT04165317] using BCG with sasanlimab [PF-06801591] in the BCG-naive setting. Some promising data were reported [from this trial] at the [2025 American Urological Association Annual Meeting (AUA)], and I am excited to learn more.

Yair Lotan, MD

Lotan: Several trials that completed enrollment [are evaluating] BCG plus checkpoint inhibition vs BCG alone. [One of these is the] CREST trial, [initial findings from] which were presented at [this year’s] AUA Annual Meeting and were positive. Results [showed that] the subcutaneous formulation [of the] checkpoint inhibitor [sasanlimab reduced] recurrence in BCG-naive patients who received that drug plus BCG.

Abstract 4500: Nivolumab plus ipilimumab (NIVO+IPI) vs gemcitabine-carboplatin (gem-carbo) chemotherapy for previously untreated unresectable or metastatic urothelial carcinoma (mUC): Final results for cisplatin-ineligible patients from the CheckMate 901 trial.

Session Time: June 1, 9:45 AM – 12:45 PM CDT

Sonpavde: The phase 3, global, open-label, randomized CheckMate 901 trial (NCT03036098) compared nivolumab plus ipilimumab vs gemcitabine/carboplatin in cisplatin-ineligible pts with previously untreated unresectable or mUC. Although, nivolumab plus ipilimumab did not meet the threshold of statistical significance for improved OS vs gemcitabine/carboplatin in [this patient population], benefit in patient subgroups is of great interest given the curative potential of combination immune checkpoint inhibitor therapy.

Guru Sonpavde, MD

Testicular Cancer

Abstract 5032: Clinical utility of a tumor-naive circulating tumor DNA (ctDNA) test to predict outcomes in patients with advanced testicular germ cell tumors.

Session time: June 2, 9:00 AM – 12:00 PM CDT

Thapa: Disease monitoring is a crucial aspect of managing advanced germ cell tumors. Standard tumor markers, such as AFP, beta-hCG, and LDH, may not be reliable tests when the disease volume is low. While we have data on ctDNA from other genitourinary malignancies, such as bladder and prostate cancers, there is limited information on the clinical utility of ctDNA in patients with advanced testicular germ cell tumors. Obtaining data from this rare genitourinary malignancy would be very beneficial in understanding treatment responses through ctDNA dynamics and could also help identify pathogenic mutations that may be actionable.