– 32% of patients were alive at three years; median duration of response was 40.5 months1
– Data represent the longest prospective follow-up for an immune checkpoint inhibitor in patients with mMCC,1 a rare and aggressive type of skin cancer2
ROCKLAND, MA, USA I October 22, 2019 I EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, today announced on behalf of the global strategic alliance with Pfizer three-year results from Part A of the pivotal Phase II JAVELIN Merkel 200 trial regarding long-term overall survival and durable responses in patients with previously treated metastatic Merkel cell carcinoma (mMCC) who received avelumab (BAVENCIO®).1 In this exploratory analysis, the overall survival (OS) rate at three years was 32%; the median duration of response (DOR) was 40.5 months; and the objective response rate (ORR) was 33.0%, which was unchanged from the one-year analysis.1 These data will be presented at the First International Symposium on Merkel Cell Carcinoma in Tampa, Florida on October 21-22, 2019.
“Historically, chemotherapy has been the only treatment for advanced Merkel cell carcinoma, with responses lasting for less than one year. In this updated analysis of the JAVELIN Merkel 200 trial, up to one-third of patients with this disease who received avelumab were alive at three years,” said Sandra P. D’Angelo, M.D., study global principal investigator, medical oncologist at Memorial Sloan Kettering Cancer Center. “The durability of clinical response and survival outcomes from avelumab treatment in this setting with three years of follow-up underscore the benefits of this medicine in the treatment of patients with metastatic Merkel cell carcinoma.”
Results from the Phase II, open-label, single-arm, multicenter JAVELIN Merkel 200 study supported the U.S. Food and Drug Administration (FDA) accelerated approval of BAVENCIO for mMCC in 2017. The analysis presented today shows that with a minimum follow-up of 36 months and a median follow-up of 40.8 months (range: 36.4–49.7), the ORR was 33.0% (95% CI: 23.3%, 43.8%) and median DOR was 40.5 months (95% CI: 18.0, NE). Among the 11.4% (10/88) of patients with complete responses (CR), half (n=5) had an ongoing response at the data cutoff. Progression-free survival (PFS) rates were 26% (95% CI: 17%, 36%) at two years and 21% (95% CI: 12%, 32%) at three years. Median OS was 12.6 months (95% CI: 7.5, 17.1), and OS rates were 36% (95% CI: 26%, 46%) at two years and 32% (95% CI: 23%, 42%) at three years.1 An analysis of OS compared to historical control data was not part of this analysis.
No unanticipated adverse events (AEs) or late infusion-related reactions occurred with long-term treatment. Treatment-related AEs of any grade occurred in 77.3% of patients (grade ≥3 in 11.4%); 21.6% had an immune-related AE of any grade (grade ≥3 in 4.5%).1
About JAVELIN Merkel 200
JAVELIN Merkel 200 is a Phase II, open-label, single-arm, multicenter study. Part A included 88 patients with Stage IV mMCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. The primary endpoint in Part A was best overall response (BOR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by a blinded independent central review committee (IRC); secondary endpoints included IRC-assessed DOR and PFS by RECIST 1.1; OS; and safety and tolerability. Part B included 116 patients with mMCC who were treatment-naïve to systemic therapy in the metastatic setting. For Part B, the major efficacy outcome measure was durable response, defined as objective response (complete response or partial response) with a duration of at least six months; secondary outcome measures included BOR, DOR, PFS and OS. Patients received BAVENCIO 10 mg/kg as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.1
About Merkel Cell Carcinoma
Metastatic MCC is a rare and aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings.2,3 MCC, which is also known as neuroendocrine carcinoma of the skin or trabecular cancer, often starts in those areas of skin that are most often exposed to the sun, including the head, neck and arms.4,5 Risk factors for MCC include sun exposure and infection with Merkel cell polyomavirus.6 Caucasian males older than 50 are at increased risk.7 MCC is often misdiagnosed as other skin cancers and grows at an exponential rate on chronically sun-damaged skin.5,8
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.9-11 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.11-13 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.
BAVENCIO Approved Indications
In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) 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. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Avelumab is currently approved for patients with MCC in more than 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
BAVENCIO® (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
About Merck KGaA, Darmstadt, Germany-Pfizer Alliance
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany and Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germany and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.
All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.
About EMD Serono, Inc.
EMD Serono – the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada – is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations based in the company’s home state of Massachusetts. www.emdserono.com.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across healthcare, life science and performance materials. Around 56,000 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 2018, Merck KGaA, Darmstadt, Germany, generated sales of € 14.8 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 KGaA, Darmstadt, Germany operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials. Since its founding 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
- D’Angelo S, et al. First International Symposium on Merkel Cell Carcinoma 2019. NCT02155647.
- Becker, J.C., Merkel cell carcinoma, Annals of Oncology. 2010:21, 7_suppl:vii81–vii85.
- American Cancer Society. What is Merkel cell carcinoma? http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-merkel-cell-carcinoma-what-is-merkel-cell-carcinoma. Last accessed September 2019.
- Schadendorf D et al. Merkel cell carcinoma: epidemiology, prognosis, therapy and unmet medical needs. European Journal of Cancer. 2017;71:53–69.
- Nghiem P, et al. Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma. Future Oncology. 2017;13(14):1263–1279.
- Villani A, et al. Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies. Dermatol Ther (Heidelb). 2019;9(2):209-222.
- American Cancer Society. Key Statistics for Merkel Cell Carcinoma. http://www.cancer.org/cancer/merkel-cell-skin-cancer/about/key-statistics.html. Last accessed September 2019.
- Schmerling RA, et al. Burden of Disease, Early Diagnosis, and Treatment of Merkel Cell Carcinoma in Latin America. Journal of Global Oncology. 2018;4:1-11.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
- 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.
- 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.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.
SOURCE: EMD Serono
Post Views: 16
– 32% of patients were alive at three years; median duration of response was 40.5 months1
– Data represent the longest prospective follow-up for an immune checkpoint inhibitor in patients with mMCC,1 a rare and aggressive type of skin cancer2
ROCKLAND, MA, USA I October 22, 2019 I EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, today announced on behalf of the global strategic alliance with Pfizer three-year results from Part A of the pivotal Phase II JAVELIN Merkel 200 trial regarding long-term overall survival and durable responses in patients with previously treated metastatic Merkel cell carcinoma (mMCC) who received avelumab (BAVENCIO®).1 In this exploratory analysis, the overall survival (OS) rate at three years was 32%; the median duration of response (DOR) was 40.5 months; and the objective response rate (ORR) was 33.0%, which was unchanged from the one-year analysis.1 These data will be presented at the First International Symposium on Merkel Cell Carcinoma in Tampa, Florida on October 21-22, 2019.
“Historically, chemotherapy has been the only treatment for advanced Merkel cell carcinoma, with responses lasting for less than one year. In this updated analysis of the JAVELIN Merkel 200 trial, up to one-third of patients with this disease who received avelumab were alive at three years,” said Sandra P. D’Angelo, M.D., study global principal investigator, medical oncologist at Memorial Sloan Kettering Cancer Center. “The durability of clinical response and survival outcomes from avelumab treatment in this setting with three years of follow-up underscore the benefits of this medicine in the treatment of patients with metastatic Merkel cell carcinoma.”
Results from the Phase II, open-label, single-arm, multicenter JAVELIN Merkel 200 study supported the U.S. Food and Drug Administration (FDA) accelerated approval of BAVENCIO for mMCC in 2017. The analysis presented today shows that with a minimum follow-up of 36 months and a median follow-up of 40.8 months (range: 36.4–49.7), the ORR was 33.0% (95% CI: 23.3%, 43.8%) and median DOR was 40.5 months (95% CI: 18.0, NE). Among the 11.4% (10/88) of patients with complete responses (CR), half (n=5) had an ongoing response at the data cutoff. Progression-free survival (PFS) rates were 26% (95% CI: 17%, 36%) at two years and 21% (95% CI: 12%, 32%) at three years. Median OS was 12.6 months (95% CI: 7.5, 17.1), and OS rates were 36% (95% CI: 26%, 46%) at two years and 32% (95% CI: 23%, 42%) at three years.1 An analysis of OS compared to historical control data was not part of this analysis.
No unanticipated adverse events (AEs) or late infusion-related reactions occurred with long-term treatment. Treatment-related AEs of any grade occurred in 77.3% of patients (grade ≥3 in 11.4%); 21.6% had an immune-related AE of any grade (grade ≥3 in 4.5%).1
About JAVELIN Merkel 200
JAVELIN Merkel 200 is a Phase II, open-label, single-arm, multicenter study. Part A included 88 patients with Stage IV mMCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. The primary endpoint in Part A was best overall response (BOR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by a blinded independent central review committee (IRC); secondary endpoints included IRC-assessed DOR and PFS by RECIST 1.1; OS; and safety and tolerability. Part B included 116 patients with mMCC who were treatment-naïve to systemic therapy in the metastatic setting. For Part B, the major efficacy outcome measure was durable response, defined as objective response (complete response or partial response) with a duration of at least six months; secondary outcome measures included BOR, DOR, PFS and OS. Patients received BAVENCIO 10 mg/kg as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.1
About Merkel Cell Carcinoma
Metastatic MCC is a rare and aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings.2,3 MCC, which is also known as neuroendocrine carcinoma of the skin or trabecular cancer, often starts in those areas of skin that are most often exposed to the sun, including the head, neck and arms.4,5 Risk factors for MCC include sun exposure and infection with Merkel cell polyomavirus.6 Caucasian males older than 50 are at increased risk.7 MCC is often misdiagnosed as other skin cancers and grows at an exponential rate on chronically sun-damaged skin.5,8
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.9-11 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.11-13 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.
BAVENCIO Approved Indications
In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) 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. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Avelumab is currently approved for patients with MCC in more than 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
BAVENCIO® (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
About Merck KGaA, Darmstadt, Germany-Pfizer Alliance
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany and Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germany and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.
All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.
About EMD Serono, Inc.
EMD Serono – the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada – is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations based in the company’s home state of Massachusetts. www.emdserono.com.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across healthcare, life science and performance materials. Around 56,000 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 2018, Merck KGaA, Darmstadt, Germany, generated sales of € 14.8 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 KGaA, Darmstadt, Germany operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials. Since its founding 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
- D’Angelo S, et al. First International Symposium on Merkel Cell Carcinoma 2019. NCT02155647.
- Becker, J.C., Merkel cell carcinoma, Annals of Oncology. 2010:21, 7_suppl:vii81–vii85.
- American Cancer Society. What is Merkel cell carcinoma? http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-merkel-cell-carcinoma-what-is-merkel-cell-carcinoma. Last accessed September 2019.
- Schadendorf D et al. Merkel cell carcinoma: epidemiology, prognosis, therapy and unmet medical needs. European Journal of Cancer. 2017;71:53–69.
- Nghiem P, et al. Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma. Future Oncology. 2017;13(14):1263–1279.
- Villani A, et al. Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies. Dermatol Ther (Heidelb). 2019;9(2):209-222.
- American Cancer Society. Key Statistics for Merkel Cell Carcinoma. http://www.cancer.org/cancer/merkel-cell-skin-cancer/about/key-statistics.html. Last accessed September 2019.
- Schmerling RA, et al. Burden of Disease, Early Diagnosis, and Treatment of Merkel Cell Carcinoma in Latin America. Journal of Global Oncology. 2018;4:1-11.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
- 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.
- 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.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.
SOURCE: EMD Serono
Post Views: 16
