The ESMO 2024 conference is set to showcase groundbreaking advancements in the field of genitourinary cancers, with a spotlight on prostate cancer, bladder cancer/urothelial cancer, and renal cell carcinoma. 

In prostate cancer, the majority of abstracts are focusing on metastatic castration-resistant prostate cancer (mCRPC) with BMS’ dual androgen receptor (AR) ligand-directed degrader and antagonist in heavily pretreated mCRPC, Bayer/Astellas’ Phase III trial comparing Xtandi vs Xtandi + XOFIGO  in asymptomatic or mildly symptomatic mCRPC, Exelixis/Ipsen’s overall survival data of Cabozantinib and Atezolizumab combo from pivotal CONTACT-02 trial in mCRPC, whereas, Amgen and Epizyme are coming up with novel classes, a STEAP1 x CD3 XmAb 2+1 Immune Therapy and EZH2 inhibitor respectively in early stages.

Within metastatic urothelial cancer space, Astellas’ exploratory analysis of PADCEV in 1st line, Seagen’s safety and efficacy data of its HER2- ADC Disitamab Vedotin in 1st line metastatic, Sichuan Baili Pharmaceutical’s EGFR x HER3 Bispecific ADC, Bicycle Therapeutics’ Bicycle Toxin Conjugate (BTC) in PADCEV naive metastatic urothelial carcinoma are much waited abstracts. Whereas, Archivel Farma is the only player presenting data in high-risk NMIBC.

Within advanced renal cell carcinoma (RCC) space, Biotheus/BioNTech is evaluating safety and efficacy data of its Bispecific (PD-L1/VEGF-A), Exelixis/Ipsen are revealing final results of Cabozantinib, 23andMe is coming up with data of a first-in-class anti-CD200R1 antibody, Aveo pharma is unveiling Tivozanib data in pretreated RCC patients, whereas both Merck and NiKang therapeutics’ are presenting data of their HIF-2α inhibitors, Belzutifan (approved) and NKT2152 (prelim results in Phase I/II)

Unveiling the latest in the Genitourinary cancer treatment landscape

• Abstract Number – LBA67
• Abstract Type – Proffered Paper session
• Indication - Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Title: Immune-Targeted Advances in mCRPC: Final Overall Survival Results from Phase III CONTACT-02 study 

Executive Summary:  The Phase III CONTACT-02 study of cabozantinib plus atezolizumab in mCRPC has shown significant improvement in radiographic PFS, with final OS data to be revealed at ESMO 2024, potentially positioning the combination as a promising second-line treatment option.

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As per DelveInsight, there were approximately 66,000 prevalent cases of mCRPC in 2023 in the United States. The mCRPC market has seen significant advancements in recent years, with a growing number of therapeutic options including novel hormonal therapies (e.g., ZYTIGA, XTANDI), PARP inhibitors (e.g., LYNPARZA, RUBRACA), or radiopharmaceuticals (e.g., XOFIGO, PLUVICTO). However, despite these advances, many patients develop resistance to these therapies, creating a critical need for new approaches.

Exelixis is conducting a Phase III CONTACT-02 study, comparing cabozantinib plus atezolizumab versus second-line novel hormonal therapy (NHT) in patients with mCRPC and measurable soft-tissue disease who have progressed after treatment with one prior NHT. Cabozantinib has been explored for its ability to inhibit multiple pathways involved in cancer progression, such as MET, VEGFR, and AXL. This study results would determine whether the combination of a tyrosine kinase inhibitor with an immune checkpoint inhibitor can compete effectively in this crowded therapeutic landscape.  

Detailed results presented at ASCO GU 2024 conference showed that CONTACT-02 is the only Phase III study of an immune checkpoint inhibitor-based regimen to show a significant and clinically meaningful improvement in radiographic PFS in prostate cancer with visceral metastasis. The study met one of its two primary endpoints, demonstrating a statistically significant benefit in PFS (median PFS was 6.3 months) in the predefined PFS intent-to-treat population. While a trend toward OS improvement was observed, the data were immature and did not meet the threshold for statistical significance. At the upcoming ESMO conference, the final overall survival data will be presented as a late-breaking abstract, providing definitive insights into the survival benefits and whether the combination could position itself as a strong alternative to current standards of care in second-line mCRPC. The company also intends to submit a sNDA to the FDA this year.

• Abstract Number – LBA73
• Abstract Type – Proffered Paper session
• Indication - Renal cell carcinoma (RCC)

Title:  AVEO’s FOTIVDA and Bristol Myers Squibb’s OPDIVO Combo Hits a Roadblock in Phase III RCC Trial, but Monotherapy Shines with Clinically Meaningful Progression-Free Survival Boost

Executive Summary: AVEO's Phase III TiNivo-2 study of FOTIVDA plus OPDIVO missed its primary efficacy endpoint, but the monotherapy data from the control arm showed meaningful PFS benefits, highlighting FOTIVDA’s continued role in renal cell carcinoma treatment

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Renal cell carcinoma is the most common type of kidney cancer accounting for around 90% of all kidney cancers. The RCC treatment landscape has become increasingly competitive, with TKIs, immunotherapy, and combination regimens becoming the cornerstone of treatment. FOTIVDA (tivozanib), an oral, next-generation VEGFR TKI, received FDA approval in March 2021, for the treatment of relapsed/refractory advanced RCC following two or more prior systemic therapies, based on data from the TIVO-3 trial. 

The company is conducting a Phase III TiNivo-2 study designed to evaluate the benefit of Bristol Myers Squibb’s PD-1 blocker OPDIVO (nivolumab) to low dose FOTIVDA versus standard dose FOTIVDA in the second-line following ICI combinations or the third-line setting following prior ICI. In July 2024, AVEO Oncology announced that its investigational tivozanib-nivolumab regimen fell short of the primary efficacy endpoint, still, AVEO struck an optimistic note in its announcement, stating that the clinical trial’s control arm using FOTIVDA as monotherapy demonstrated a clinically meaningful outcome in median PFS in the second-line following ICI combination therapy. This specific data adds to the growing body of evidence of the importance of a highly selective anti-VEGFR TKI therapy as an effective, well-tolerated treatment option for relapsed or refractory RCC. The company will reveal more detailed findings and analyses from TiNivo-2 at the upcoming ESMO conference. 

AVEO’s Phase III disappointment follows a similar failure by BMS, which in January 2024 reported that OPDIVO did not significantly boost disease-free survival in localized RCC patients versus placebo in the Phase III CheckMate-914 trial. In contrast, Merck appears to be making strides in RCC, with its HIF-2α inhibitor WELIREG (belzutifan) winning the FDA’s approval in December 2023 for patients with advanced disease who had previously been treated with a PD-1 blocker and a VEGF inhibitor. A month later, the pharma’s blockbuster drug KEYTRUDA also secured a late-stage win in RCC.

• Abstract Number – 1692P
• Abstract Type – Poster
• Indication - Renal cell carcinoma (RCC)

Title: Biotheus/BioNTech’s first-in-class bispecific antibody, PM8002/BNT327, to show promise in the Renal Cell Carcinoma treatment landscape?

Executive Summary: Results from a Phase I/II trial of a first-in-class bispecific antibody to be presented at ESMO 2024 may show potential to outperform current single-target therapies.

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One of the new emerging classes to be seen in RCC space at the ESMO 2024 includes Biotheus/BioNTech’s first-in-class bispecific antibody, PM8002/ BNT327, targeting PD-L1, a key immune checkpoint receptor, and VEGF-A, a pivotal driver of angiogenesis, among others. It is currently being evaluated as a monotherapy for advanced RCC in a Phase Ib/IIa trial. Results from this trial will be featured as a poster at the upcoming ESMO conference. 

Early data from the Phase Ib component indicate a manageable safety profile with manageable adverse events. This dual-target strategy could potentially overcome the limitations of current therapies, which include immune checkpoint inhibitors like KEYTRUDA and OPDIVO, and VEGF inhibitors such as FOTIVDA. The current RCC treatment landscape is crowded and competitive, with established therapies facing challenges such as resistance and suboptimal efficacy in certain patient subsets. PM8002/BNT327’s ability to simultaneously block immune evasion and tumor angiogenesis may offer a significant advantage, making it a potentially strong competitor in a market dominated by single-target therapies and combination regimens. The ongoing trial results will be crucial in determining whether PM8002/BNT327 can deliver a substantial clinical benefit and set a new benchmark for RCC treatment.

Top 10 Key Abstracts for Genitourinary Cancers