American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium 2026 | iPharmaCenter

Keytruda and Welireg Combination Cuts Risk of RCC Recurrence by 28% in Adjuvant Setting

Merck reported new Phase 3 results from the LITESPARK-022 trial showing that adding Welireg (belzutifan) to Keytruda (pembrolizumab) as adjuvant therapy significantly reduced the likelihood of recurrence or death in certain patients with clear cell renal cell carcinoma (RCC) following nephrectomy.

The study demonstrated a 28% lower risk of disease recurrence or death compared with Keytruda used alone.

These data mark a major milestone, representing the first positive late-stage results for Welireg in an earlier-stage population, the first HIF-2α inhibitor combined with immunotherapy to show benefit, and the first combination regimen in early-stage disease, irrespective of tumor type, to outperform Keytruda monotherapy in improving disease-free survival (DFS).

Based on these findings, the U.S. FDA has granted priority review to supplemental applications seeking approval for WELIREG in combination with Keytruda (or Keytruda QLEX) as adjuvant treatment for certain RCC patients.

Phase 3 LITESPARK-022 Trial Results testing combination of Welireg and Keytruda

At the first pre-specified interim analysis, after a median follow-up of 28.4 months, the adjuvant combination of Keytruda and Welireg achieved a significant improvement in DFS, the study’s primary endpoint.

Patients receiving the combination experienced a 28% relative risk reduction in disease recurrence or death compared to those who received Keytruda plus placebo. The median DFS was not reached in either arm.

24-month disease-free survival

• KEYTRUDA plus WELIREG: 80.7%

• KEYTRUDA plus placebo: 73.7%

  
  

About the LITESPARK-022 Study

The LITESPARK-022 trial (NCT05239728) is a multicenter, randomized, double-blind Phase 3 study comparing Keytruda in combination with Welireg against Keytruda plus placebo as adjuvant therapy in patients with clear cell RCC following surgical removal of the kidney. Keytruda (400 mg intravenously every 6 weeks) plus placebo.

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 Welireg (belzutifan), combined with Lenvima (lenvatinib), Demonstrates 30% Reduction in Risk of Disease Progression or Death Compared to Cabozantinib in Pretreated Advanced Renal Cell Carcinoma

Merck and Eisai have announced encouraging results from the Phase 3 LITESPARK-011 clinical trial, showcasing the efficacy of combining Welireg (belzutifan), Merck’s oral HIF-2α inhibitor, with Lenvima (lenvatinib), Eisai’s multi-target tyrosine kinase inhibitor (TKI), in patients with advanced renal cell carcinoma (RCC) previously treated with anti–PD-1 or PD-L1 therapies. This marks the first successful late-stage clinical trial pairing a HIF-2α inhibitor with a multi-target TKI and the first to achieve superior progression-free survival over a contemporary TKI regimen in this patient population.

Significant PFS Improvement vs. Cabozantinib

During a scheduled interim analysis with a median follow-up of 29.0 months, the dual regimen achieved a statistically significant and clinically relevant reduction in the risk of disease progression or death by 30% compared with cabozantinib. The median progression-free survival (PFS) was 14.8 months in the WELIREG plus LENVIMA arm versus 10.7 months in the cabozantinib group.

A favorable trend toward extended overall survival (OS) was also observed, with a median OS of 34.9 months for the combination versus 27.6 months for cabozantinib. As OS data continue to mature, a follow-up analysis will provide a definitive assessment as outlined in the study protocol.

Regulatory Developments

Using data from the LITESPARK-011 trial, the U.S. Food and Drug Administration (FDA) has accepted two supplemental New Drug Applications (sNDAs) for Welireg plus Lenvima to treat adults with advanced RCC containing a clear-cell component whose disease progressed following PD-1 or PD-L1 inhibitor therapy. The FDA’s target action date under the Prescription Drug User Fee Act (PDUFA) is October 4, 2026, for both applications. Merck and Eisai intend to engage with regulatory authorities globally to pursue additional filings based on these findings.

Key Secondary Endpoints: Response and Duration

At the first interim assessment (median follow-up: 19.6 months), the Welireg plus Lenvima regimen also demonstrated a statistically significant improvement in objective response rate (ORR) compared to cabozantinib. The confirmed ORR was 52.6% versus 39.6%, respectively.

At the second analysis point (median follow-up: 29.0 months), the median duration of response (DOR) was 23.0 months in the combination arm versus 12.3 months with cabozantinib.

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Johnson & Johnson Reports First-in-Human Data for Pasritamig, Demonstrating Early Signs of Efficacy in Advanced Prostate Cancer

Johnson & Johnson shared the first clinical data on pasritamig (JNJ-78278343), its novel bispecific T-cell–redirecting antibody, from an ongoing Phase 1 study in metastatic castration-resistant prostate cancer (mCRPC). The investigational agent showed encouraging antitumor activity and a manageable safety profile in heavily pretreated patients, signaling a potential new therapeutic approach targeting human kallikrein 2 (KLK2).

Pasritamig represents a new class of T-cell–engaging therapies, designed to connect CD3 on T-cells with KLK2, a prostate-specific protein rarely found in other tissues. By guiding immune cells directly toward KLK2-expressing tumors, pasritamig aims to enhance immune-mediated tumor cell killing while minimizing systemic toxicity. The therapy was developed with community oncology settings in mind, using an outpatient-compatible dosing schedule that may improve patient convenience.

Phase 1 First-in-Human Trial Overview

The Phase 1 trial (NCT04898634) enrolled 174 patients, aged 36 to 89 years, all of whom had received prior systemic therapy for advanced disease (median of four prior lines, range 1–13).

Efficacy Results

Among the 33 patients treated in the RP2D efficacy cohort, 42.4% achieved a ≥50% decline in PSA levels, indicating robust biological activity. The median radiographic progression-free survival (rPFS) was 7.9 months, with over 21% of participants remaining on therapy at the time of analysis.

These early data suggest that treatment with pasritamig leads to durable disease control and may achieve outcomes comparable to or better than historical benchmarks in patients who have exhausted multiple prior therapies.

Clinical Context and Unmet Needs

Metastatic castration-resistant prostate cancer remains a difficult-to-treat stage of disease, with many patients eventually progressing after standard hormonal agents, chemotherapy, or targeted radionuclide therapy. Reported overall survival for this patient group typically ranges between 13.5 and 31.6 months, shorter for those with resistant disease, highlighting the need for new, safer, and more selective immunotherapies.

About Pasritamig (JNJ-78278343)

Pasritamig is an investigational bispecific antibody created to bind both KLK2 on prostate tumor cells and CD3 on T-cells, redirecting the immune response against cancer-specific targets. By focusing on a highly prostate-restricted antigen, pasritamig seeks to expand the benefits of T-cell–engaging immunotherapy to men with advanced prostate cancer, potentially transforming the treatment landscape for late-line mCRPC.

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Novartis Real-World Data Supports Earlier Lutetium Lu 177 Vipivotide Tetraxetan Use in Prostate Cancer Before Chemotherapy

Recent U.S. real-world studies from Novartis' PRECISION platform highlight the effectiveness of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), particularly in chemotherapy-naïve patients.

Among 500 taxane-naïve mCRPC patients previously treated with at least one androgen receptor pathway inhibitor (ARPI), median progression-free survival (PFS) reached 13.5 months.

Key Efficacy Findings

Patients receiving the radioligand therapy after just one ARPI achieved superior outcomes, with median PFS of 15.8 months, compared to 12.7 months for those post-multiple ARPIs. PSA50 response rates remained consistently high across cohorts at 62.6% overall, 61.4% for single ARPI, and 63.8% for multiple ARPIs.

Cohort	Median PFS	PSA50 Response
All patients (n=500)	13.5 months	62.6%
1 ARPI (n=256)	15.8 months	61.4%
>1 ARPI (n=244)	12.7 months	63.8%