MERCK

Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced findings of a new analysis of long-term follow-up data from the Phase III JAVELIN Bladder 100 trial. These analyses reinforce the proven survival benefits of BAVENCIO^® (avelumab) in the first-line maintenance setting for patients with locally advanced or metastatic urothelial carcinoma (UC). With median follow-up of at least 38 months from randomization, patients who were progression-free following platinum-based chemotherapy who received BAVENCIO first-line maintenance plus best supportive care (BSC) had longer median overall survival (OS) than those who received BSC alone in the maintenance setting. This benefit was seen regardless of whether their initial chemotherapy regimens included cisplatin or carboplatin. This analysis, as well as multiple studies of BAVENCIO in the real-world setting, are being presented at the 2023 American Society of Clinical Oncology’s annual Genitourinary Cancers Symposium, February 16-18, 2023.

“Based on the significant improvement in overall survival demonstrated in the Phase III JAVELIN Bladder 100 study, platinum-based chemotherapy followed by avelumab maintenance treatment in patients without evidence of disease progression, has become a standard of care for advanced urothelial carcinoma. The findings presented today reinforce that all patients eligible for platinum-based chemotherapy, either cisplatin or carboplatin, can benefit from avelumab maintenance therapy. These findings reported here provide a reference point for outcomes of ongoing and future clinical trials in advanced bladder cancer,” said Srikala Sridhar, MD, MSc, FRCPC, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

In the overall population, patients who received BAVENCIO plus BSC had a median OS of 29.7 months (95% CI, 25.2-34.0) as measured from the start of first-line chemotherapy, compared with 20.5 months (95% CI, 19.0-23.5) in patients who received BSC alone (HR, 0.77; 95% CI, 0.636-0.921). This result further supports the JAVELIN Bladder 100 regimen of BAVENCIO first-line maintenance in patients with advanced UC who are progression-free following first-line platinum-based chemotherapy as standard of care.

The analysis also confirmed that the overall survival of BAVENCIO first-line maintenance were similar regardless of whether patients received cisplatin- or carboplatin-based chemotherapy.

• In patients who received cisplatin plus gemcitabine (n=389), median OS from start of chemotherapy was 31.0 months (95% CI, 24.9-37.1) in the BAVENCIO plus BSC arm (n=183), compared with 23.0 months (95% CI, 19.2-30.9) for BSC alone (n=206) (HR, 0.79; 95% CI, 0.613-1.024).
• In patients who received carboplatin plus gemcitabine (n=269), median OS from start of chemotherapy was 25.8 months (95% CI, 22.8-33.3) for BAVENCIO plus BSC (n=147), compared with 17.6 months (95% CI, 14.8-21.3) for BSC alone (n=122) (HR, 0.69; 95% CI, 0.514-0.920).

Long-term safety was similar in both the cisplatin plus gemcitabine and carboplatin plus gemcitabine subgroups, with no new safety concerns identified. Grade 3 or greater treatment-related adverse events were 16 percent and 23 percent for cisplatin and carboplatin cohorts, respectively.

“BAVENCIO remains the only immunotherapy to show improved overall survival in advanced UC patients in the first-line maintenance setting in a Phase III trial. The large, randomized Phase III JAVELIN Bladder 100 trial established BAVENCIO first-line maintenance treatment following platinum-based chemotherapy as a standard of care, and long-term and real-world data such as these presented at ASCO GU 2023, continue adding to the evidence supporting its benefits for patients with advanced bladder cancer,” said Tamas Sütö, MD, PhD, Senior Vice President & Head of Medical Unit Oncology, Merck.

Additional data presented at the meeting include updates from real-world studies of patient populations in France, Italy, Germany, and the U.S. This includes the first full analysis from the AVENANCE real-world study investigating the efficacy and safety of BAVENCIO first-line maintenance therapy in advanced UC patients in France, and the READY study of real-world data from a compassionate use program in Italy, which supports the findings of JAVELIN Bladder 100 in real-world settings.

• In the ongoing (median follow-up 15.2 months) noninterventional AVENANCE study of 593 patients in France with advanced UC that had not progressed with first-line platinum-based chemotherapy who received BAVENCIO as a first-line maintenance treatment, median OS from start of BAVENCIO treatment was 20.7 months (95% CI, 17.1-not estimable) and the 12-month OS rate was 65.4% (95% CI, 61.0-69.4). Median progression-free survival (PFS) was 5.7 months (95% CI, 5.3-7.0).
• In the READY study of 464 patients in Italy who received BAVENCIO first-line maintenance treatment following platinum-based chemotherapy, median OS was not reached and the 12-month OS rate from the start of BAVENCIO treatment was 69.2% (95% CI, 64.8%-73.7%). The median PFS was 8.1 months (95% CI, 6.1-10.4) with a 12-month PFS rate of 44.3% (95% CI, 39.5-49.1).

Data for BAVENCIO as well as real-world analyses in urothelial cancer being presented at ASCO GU include:

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 annually² 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 In November 2014, Merck KGaA, Darmstadt, Germany and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
The European Commission (EC) has authorized the use of BAVENCIO as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. BAVENCIO in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is also authorized by the EC for use as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

In the US, BAVENCIO is indicated 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 RCC. Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 healthcare, life science and electronics. Around 60,000 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 advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck generated sales of € 19.7 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Electronics.

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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