Multiple New Analyses Reinforce the Role of BAVENCIO® (avelumab) First-Line Maintenance as a Standard of Care in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Merck, a leading science and technology company, today announced new real-world data that continue to reinforce the JAVELIN Bladder regimen of first-line platinum-based chemotherapy followed by BAVENCIO^® (avelumab) maintenance as a standard of care for eligible patients with locally advanced or metastatic urothelial carcinoma (UC) who do not progress on first-line chemotherapy. Data include real-world studies that confirm median overall survival (OS) of approximately 30 months in patients without progression after first-line chemotherapy. Additional analyses offer insights into treatment sequencing outcomes in the real world, with the first analysis of OS by next-line treatment, including in patients who received an antibody-drug conjugate (ADC) such as enfortumab vedotin after the JAVELIN Bladder regimen. These and other analyses will be presented at the 2024 American Society of Clinical Oncology’s annual Genitourinary Cancers Symposium, January 25-27, in San Francisco.

“Avelumab in the first-line maintenance setting is a standard of care for patients with locally advanced or metastatic bladder cancer, with a well-established efficacy and safety profile and supported by years of real-world experience. These new analyses add to the large body of evidence, showing avelumab maintenance treatment can help extend overall survival while potentially providing a favorable quality of life,” said Philippe Barthélémy, Institut de Cancérologie Strasbourg Europe, France. “The ongoing exploratory analysis of the real-world AVENANCE study may provide new insights indicating that the initial use of the JAVELIN Bladder regimen, followed by a second-line antibody-drug conjugate treatment like enfortumab vedotin, could greatly enhance overall survival outcomes for patients. These findings underscore the importance of strategic treatment sequencing in optimizing patient outcomes.”

Real-world insights into treatment sequencing following the JAVELIN Bladder regimen

Real-world data and analyses by subsequent treatment from the ongoing, real-world, ambispective (retrospective and prospective) AVENANCE study in France continue to support the use of BAVENCIO first-line maintenance while also demonstrating the impact of subsequent therapies once BAVENCIO treatment is discontinued. With a median follow-up since initiation of BAVENCIO of 26.3 months, median OS from the start of BAVENCIO maintenance was 21.3 months (n=595; 95% CI, 17.6 to 24.6) in patients who did not progress on first-line platinum-based chemotherapy and received BAVENCIO first-line maintenance. In an exploratory analysis, median OS from the start of platinum-based chemotherapy was 26.5 months (95% CI, 23.4 to 30.1). Subgroup analyses evaluated outcomes in the 330 patients who received second-line therapy, with median OS from the start of BAVENCIO maintenance of 31.3 months (95% CI, 29.1 to NE) in the 62 patients who received a second-line ADC (enfortumab vedotin: n=56; sacituzumab govitecan: n=6) and 16.7 months (95% CI, 13.6 to 22.8) in the 81 patients who received second-line platinum-based chemotherapy. Among the patients who received a second-line ADC, median OS measured from the start of chemotherapy was 40.8 months (95% CI, 32.6 to 42.1) in the exploratory analysis.

Long-term efficacy with the JAVELIN Bladder regimen in the real world

Real-world analyses of BAVENCIO first-line maintenance show median OS from the start of chemotherapy of at least 30 months in this population of patients who do not progress on first-line platinum-based chemotherapy, consistent with previously reported results of a long-term exploratory analysis from JAVELIN Bladder 100.

• PATRIOT-II U.S. Real-World Study: The observational, retrospective PATRIOT-II study analyzed medical records from 160 U.S. patients, with median follow-up from the start of BAVENCIO maintenance of 16 months (range, 11-21 months). Patients who received BAVENCIO first-line maintenance treatment following chemotherapy achieved a median OS of 30.5 months measured from the start of first-line chemotherapy (95% CI, 23.4 to 37.6). Median OS was 24.4 months measured from the start of maintenance treatment (95% CI, 20.4 to 28.4).
• READY CUP Italy Real-World Study: The prospective, noninterventional compassionate use program (CUP) provided Italian patients with locally advanced or metastatic UC early access to BAVENCIO first-line maintenance before reimbursement. With median follow-up of 20.3 months (95% CI, 19.8 to 20.9), median OS measured from start of first-line chemotherapy was 30.9 months (95% CI, 25.7 to NE) in this population without progression after chemotherapy. Median OS from the start of maintenance treatment was 26.2 months (95% CI, 20.0 to NE).

Analyses of quality of life and efficacy in JAVELIN Bladder 100

• Patient-Reported Outcomes from JAVELIN Bladder 100: This post-hoc analysis assessed long-term patient-reported outcomes (PRO) data using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L).An analysis of scores over all cycles prior to end of BAVENCIO treatment PRO patient-reported outcomes scores were BAVENCIO treatment:, with a -2.15 mean change from baseline of -2.15 (95% CI, -3.25 to -1.04) in the FBISI-18 score and -.07 (95% CI, -.09 to -.05) in the EQ-5D-5L index score. In patients with 12 months or more of BAVENCIO treatment, there was a 1.28 mean change from baseline (95% CI, .08 to 2.49) in the FBISI-18 score and a -.02 mean change in the EQ-5D-5L index score further supporting the use of the JAVELIN Bladder regimen in eligible patients with advanced UC until progression or unacceptable toxicity.
• High BMI Subgroup Analysis from JAVELIN Bladder 100: This exploratory subgroup analysis (n=122) showed the efficacy and safety of BAVENCIO maintenance treatment in patients with a high body mass index (BMI; ≥30 kg/m²)—a key patient population given that high BMI is a risk factor for bladder cancer, and 25% of the world’s population is anticipated to have a high BMI by 2035. In patients with high BMI at baseline, median OS for patients receiving BAVENCIO maintenance therapy plus BSC was 20.8 months from the start of maintenance treatment (95% CI, 16.9 to 34.4), compared with 12.7 months (95% CI, 8.1 to 26.6 months) for BSC alone (HR: 0.77; 95% CI, 0.49 to 1.21). Long-term safety for patients with high BMI was consistent with results from the overall population.

“The JAVELIN Bladder 100 study helped transform the standard of care for patients with advanced bladder cancer, at a time when there had been few advancements in decades. By continuing to share new research on BAVENCIO, including data on health-related quality of life, key patient populations, and treatment sequencing, we can further support clinicians in making informed treatment decisions for each individual patient,” said Tamas Sütö, MD, PhD, Senior Vice President & Head of Medical Unit Oncology, Merck.

All company presentations in urothelial cancer at ASCO GU 2024 are listed below.

Title	Lead Author, Abstract # and Session Details (all times PT)
Real-world treatment patterns (tx) and clinical outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) in Germany: Results of a retrospective observational study (CONVINCE)	S. Machtens Abstract #551 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Avelumab first-line maintenance (1LM) in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) in the Czech Republic: Interim real-world results from a national reimbursement registry	A Zemankova Abstract #557 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Updated subgroup analyses from READY: REAl-world Data from an Italian compassionate use program (CUP) of avelumab first-line maintenance (1LM) treatment for locallY advanced or metastatic urothelial carcinoma (la/mUC)	S Bracarda Abstract #558 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Updated results from AVENANCE: Real-world effectiveness of avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) and analysis of subsequent treatment	P Barthélémy Abstract #561 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term patient-reported outcomes (PROs) in the phase 3 JAVELIN Bladder 100 trial	P Grivas   Abstract #581 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Clinical outcomes with split-dose cisplatin-based regimens in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): results of a systematic literature review (SLR) and network meta-analysis (NMA)	R O’Dwyer Abstract #589 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI)	J Aragon-Ching   Abstract #600 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Real-world (rw) treatment patterns, sequencing, and outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) receiving avelumab first-line maintenance (1LM) in the US	HH Moon   Abstract #605 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Platinum eligibility (PE) criteria for patients with metastatic urothelial carcinoma (mUC): results of a physician survey in 5 European countries	S Gupta   Abstract #696 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45
Avelumab first-line maintenance therapy for locally advanced/metastatic urothelial carcinoma: results from the real-world PATRIOT-II study	P Grivas Abstract #697 Poster Session B: Urothelial Carcinoma Friday, Jan 26, 2024 11:30-13:00, 17:45-18:45

About JAVELIN Bladder 100

JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus BSC versus BSC alone in patients with locally advanced or metastatic UC. The primary endpoint was OS in the two primary populations of all patients and patients with PD-L1+ tumors defined by the Ventana SP263 assay. Secondary endpoints included progression-free survival, anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers and patient-reported outcomes in the co-primary populations. All primary and secondary endpoints are measured from the time of randomization.

About Urothelial Carcinoma

Bladder cancer is the tenth most common cancer worldwide.¹ In 2020, there were over half a million new cases of bladder cancer diagnosed, with around 200,000 deaths from the disease globally.¹ In the US, an estimated 83,730 cases of bladder cancer were diagnosed in 2021, with around 10,000 locally advanced or metastatic cases presented annually.² UC, which accounts for about 90% of all bladder cancers,³ becomes harder to treat as it advances, spreading through the layers of the bladder wall.⁴ Only 25% to 55% of patients receive any second-line therapy after first-line chemotherapy.⁵ In the US and EU5 markets, approximately 40% to 50% of patients receive an immune checkpoint inhibitor in second-line therapy.² For patients with advanced UC, the five-year survival rate is 6.4%.²

About BAVENCIO^® (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.^6-8

BAVENCIO Approved Indications

BAVENCIO^® (avelumab) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

BAVENCIO in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, BAVENCIO is indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

BAVENCIO is currently approved for at least one indication for patients in more than 50 countries.

BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

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About Merck

Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 64,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2022, Merck generated sales of € 22.2 billion in 66 countries.

The company holds the global rights to the name and trademark “Merck” internationally. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare and EMD Electronics in electronics. Since its founding in 1668, scientific exploration and responsible entrepreneurship have been key to the company’s technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.

References

1. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021;0:1–41.
2. SEER. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed February 2022.
3. Cancer.net. Bladder cancer: introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed February 2022.
4. American Cancer Society. What is bladder cancer? https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed February 2022.
5. Cheeseman S, et al. Current treatment and outcomes benchmark for locally advanced or metastatic urothelial cancer from a large UK-based single centre. Front Oncol. 2020;10:167.
6. Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157.
7. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
8. Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295.

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