Long-Term Follow-Up

Long-Term Follow-Up Data Reinforce Continued Overall Survival Benefit of BAVENCIO(R) (avelumab) First-Line Maintenance Treatment in Patients with Advanced Urothelial Carcinoma

• 38-month median follow-up data from the Phase III      JAVELIN Bladder 100 trial demonstrated prolonged median OS of 23.8 months      with BAVENCIO plus best supportive care (BSC) in the first-line      maintenance setting versus a median OS of 15.0 months with BSC alone

• BAVENCIO continues to be the first and only      immunotherapy to improve survival in the first-line setting in locally      advanced or metastatic UC in a Phase III study

Not intended for US-, Canada- and UK-based media

DARMSTADT, Germany -- (BUSINESS WIRE) --

Merck, a leading science and technology company, today announced the results of an exploratory analysis from the Phase III JAVELIN Bladder 100 trial with 19 additional months of follow-up data from the initial primary analysis. This analysis reinforced the original results and showed that BAVENCIO^® (avelumab) plus best supportive care (BSC) in the first-line maintenance setting prolonged median overall survival (OS) by 8.8 months versus BSC alone for patients with locally advanced or metastatic urothelial carcinoma (UC) whose tumors had not progressed on a platinum-based chemotherapy. These results were presented at the 2022 American Society of Clinical Oncology’s annual Genitourinary Cancers Symposium taking place February 17-19, 2022.

“Since the introduction of the first-line maintenance regimen of BAVENCIO plus best supportive care, it has been recommended with the highest level of evidence in the NCCN, ESMO, EAU and JUA guidelines, and BAVENCIO first-line maintenance has become a standard of care in the locally advanced and metastatic UC treatment setting. The results from this analysis further reinforce the benefit of first-line maintenance therapy, and of BAVENCIO as the only immunotherapy in the maintenance setting shown to improve survival in this disease,” said Thomas Powles, MBBS, MRCP, MD, Professor of Genitourinary Oncology, Lead for Solid Tumor Research at Barts Cancer Institute, Queen Mary University of London, and Director of Barts Cancer Centre, London, UK.

At 38 months median follow-up, patients who received first-line maintenance BAVENCIO plus BSC showed consistent overall survival benefit over patients on BSC alone.

• Median OS was 23.8 months (95% CI, 19.9 to 28.8)      vs 15.0 months (95% CI, 13.5 to 18.2) (HR 0.76; 95% CI, 0.631 to 0.915).¹      

• 43.7% of patients (95% CI, 38.2% to 49.0%) in the      BAVENCIO arm were alive at 30 months vs 33.5% (95% CI, 28.4% to 38.7%) of      patients who received BSC alone.¹

In the population of patients with PD-L1+ tumors (n=358):

• Median OS was 30.9 months (95% CI, 24.0-39.8) vs      18.5 months (95% CI, 14.1-24.2) (HR 0.69; 95% CI, 0.521 to 0.901).¹      

• More than half (51.3%; 95% CI, 43.7% to 58.4%) of      patients who received BAVENCIO were alive at 30 months vs 38.5% (95% CI,      30.9% to 46.1%) in the BSC arm.¹

Median overall survival was measured from the time of randomization, after completion of four to six cycles of platinum-based chemotherapy.

The safety profile for BAVENCIO was consistent with the overall JAVELIN monotherapy clinical development program, with no new safety signals. Patients continued treatment until disease progression, unacceptable toxicity or any other criteria for withdrawal occurred. In the primary population of all randomized patients, 19.5% of patients received ≥2 years of treatment, with 10.2% of patients discontinuing due to treatment-related adverse event with onset after ≥12 months of treatment.

“Locally advanced and metastatic urothelial carcinoma has a low five-year survival rate and high recurrence rate, requiring additional medicines to maintain the benefits of chemotherapy and improve survival rates. The continued improvement in survival in the JAVELIN Bladder 100 trial further supports the use of BAVENCIO as maintenance therapy in patients whose disease has not progressed on first-line platinum-containing chemotherapy and reinforces our commitment to further evaluation of BAVENCIO in advanced bladder cancer,” said Victoria Zazulina, MD, Head of Development Unit Oncology, Merck.

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.² In 2020, there were over half a million new cases of bladder cancer diagnosed, with around 200,000 deaths from the disease globally.² 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.³ UC, which accounts for about 90% of all bladder cancers,⁴ becomes harder to treat as it advances, spreading through the layers of the bladder wall.⁵ Only 25% to 55% of patients receive any second-line therapy after first-line chemotherapy.⁶ In the US and EU5 markets, approximately 40% to 50% of patients receive an immune checkpoint inhibitor in second-line therapy.³ For patients with advanced UC, the five-year survival rate is 6.4%.³

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.^7-9 In November 2014, Merck 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.

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

About Merck
Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 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 2020, Merck generated sales of € 17.5 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. Powles T, Park SH, Voog E, et al. Avelumab first-line      (1L) maintenance for advanced urothelial carcinoma (UC): long-term follow      up results from the JAVELIN Bladder 100 trial. Presented at ASCO GU 2022.

2. 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.

3. SEER. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html.      Accessed February 2022.

4. Cancer.net. Bladder cancer: introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction.      Accessed February 2022.

5. American Cancer Society. What is bladder cancer? https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html.      Accessed February 2022.

6. 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.

7. 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.

8. Dolan DE, Gupta S. PD-1 pathway inhibitors:      changing the landscape of cancer immunotherapy. Cancer Control.      2014;21(3):231-237.

9. 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.