DARMSTADT, Germany, and NEW YORK, NY, USA I December 21, 2018 I Merck and Pfizer Inc. (NYSE: PFE) today announced that data from a planned interim analysis of the Phase III JAVELIN Ovarian 100 study of avelumab* did not support the study’s initial hypothesis, and therefore the alliance made the decision to terminate the trial in alignment with the independent Data Monitoring Committee.
The Merck-Pfizer alliance was the first to test an immunotherapy in this indication, given the significant unmet need in the treatment of ovarian cancer. Four out of five women with ovarian cancer are diagnosed at advanced stages.1 Most women with advanced ovarian cancer ultimately die within five years due to refractory, resistant or recurrent disease.2,3
Topline results showed that the study, which is evaluating avelumab in combination with and/or following platinum-based chemotherapy in previously untreated patients with ovarian cancer, would not achieve superiority in the pre-specified primary endpoint of progression-free survival. While detailed analyses of the data are ongoing, no new safety signals were observed, and the safety profile for avelumab in this trial appears consistent with that observed in the overall JAVELIN clinical development program. The alliance has notified health authorities and trial investigators of the interim findings and the decision to discontinue the trial. Detailed results will be shared with the scientific community. The JAVELIN Ovarian PARP 100 study and earlier phase studies investigating avelumab in various combinations are ongoing.
*Avelumab is under clinical investigation for treatment of ovarian cancer. There is no guarantee that avelumab will be approved for ovarian cancer by any health authority worldwide.
About JAVELIN Ovarian 100
JAVELIN Ovarian 100 is a Phase III, multicenter, randomized, three-arm study investigating avelumab in combination with and/or as a maintenance treatment following carboplatin/paclitaxel chemotherapy in 998 previously untreated patients with locally advanced or metastatic (Stage III or Stage IV) epithelial ovarian cancer, fallopian tube cancer (FTC), or primary peritoneal cancer. The three arms are carboplatin/paclitaxel followed by observation; carboplatin/paclitaxel followed by avelumab maintenance; and avelumab plus carboplatin/paclitaxel followed by avelumab maintenance. The primary objectives are to demonstrate superior PFS for one or both avelumab-based treatment regimens compared with carboplatin/paclitaxel followed by observation.
About the JAVELIN Clinical Development Program
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types. In addition to ovarian cancer, these tumor types include breast, gastric/gastro-esophageal junction and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, renal cell carcinoma and urothelial carcinoma.
About Ovarian Cancer
Every year, more than 295,000 women are diagnosed with ovarian cancer worldwide.4 The disease is generally advanced when it is diagnosed, as it often has few to no symptoms at the early stages, making it difficult to detect. Symptoms also can be vague or non-specific, making it easy to confuse with less serious non-cancerous conditions. The five-year survival rate ranges from approximately 30% to 50%, but for those with metastatic disease, it drops to less than 20%.5,6
About Avelumab (BAVENCIO®)
Avelumab (BAVENCIO®) is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab 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, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.7-9 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.9-11 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Approved Indications in the US
In the US, the FDA granted accelerated approval for avelumab (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 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
Important Safety Information from the US FDA-Approved Label
The warnings and precautions for BAVENCIO® include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab for mMCC and patients with locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
References
1. American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-special-section-ovarian-cancer-2018.pdf. Accessed December 2018.
2. Ledermann, JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (Supplement 6): vi24–vi32, doi:10.1093/annonc/mdt333.
3. Ozol, RJ. Challenges for chemotherapy in ovarian cancer. Annals of Oncology 2006;17(5):v181-187.
4. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project. Available at: https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed December 2018.
5. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project. Available at: https://www.wcrf.org/dietandcancer/ovarian-cancer. Accessed December 2018.
6. American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed December 2018.
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.
9. 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.
10. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
11. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.
SOURCE: Merck KGaA
Post Views: 24
DARMSTADT, Germany, and NEW YORK, NY, USA I December 21, 2018 I Merck and Pfizer Inc. (NYSE: PFE) today announced that data from a planned interim analysis of the Phase III JAVELIN Ovarian 100 study of avelumab* did not support the study’s initial hypothesis, and therefore the alliance made the decision to terminate the trial in alignment with the independent Data Monitoring Committee.
The Merck-Pfizer alliance was the first to test an immunotherapy in this indication, given the significant unmet need in the treatment of ovarian cancer. Four out of five women with ovarian cancer are diagnosed at advanced stages.1 Most women with advanced ovarian cancer ultimately die within five years due to refractory, resistant or recurrent disease.2,3
Topline results showed that the study, which is evaluating avelumab in combination with and/or following platinum-based chemotherapy in previously untreated patients with ovarian cancer, would not achieve superiority in the pre-specified primary endpoint of progression-free survival. While detailed analyses of the data are ongoing, no new safety signals were observed, and the safety profile for avelumab in this trial appears consistent with that observed in the overall JAVELIN clinical development program. The alliance has notified health authorities and trial investigators of the interim findings and the decision to discontinue the trial. Detailed results will be shared with the scientific community. The JAVELIN Ovarian PARP 100 study and earlier phase studies investigating avelumab in various combinations are ongoing.
*Avelumab is under clinical investigation for treatment of ovarian cancer. There is no guarantee that avelumab will be approved for ovarian cancer by any health authority worldwide.
About JAVELIN Ovarian 100
JAVELIN Ovarian 100 is a Phase III, multicenter, randomized, three-arm study investigating avelumab in combination with and/or as a maintenance treatment following carboplatin/paclitaxel chemotherapy in 998 previously untreated patients with locally advanced or metastatic (Stage III or Stage IV) epithelial ovarian cancer, fallopian tube cancer (FTC), or primary peritoneal cancer. The three arms are carboplatin/paclitaxel followed by observation; carboplatin/paclitaxel followed by avelumab maintenance; and avelumab plus carboplatin/paclitaxel followed by avelumab maintenance. The primary objectives are to demonstrate superior PFS for one or both avelumab-based treatment regimens compared with carboplatin/paclitaxel followed by observation.
About the JAVELIN Clinical Development Program
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types. In addition to ovarian cancer, these tumor types include breast, gastric/gastro-esophageal junction and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, renal cell carcinoma and urothelial carcinoma.
About Ovarian Cancer
Every year, more than 295,000 women are diagnosed with ovarian cancer worldwide.4 The disease is generally advanced when it is diagnosed, as it often has few to no symptoms at the early stages, making it difficult to detect. Symptoms also can be vague or non-specific, making it easy to confuse with less serious non-cancerous conditions. The five-year survival rate ranges from approximately 30% to 50%, but for those with metastatic disease, it drops to less than 20%.5,6
About Avelumab (BAVENCIO®)
Avelumab (BAVENCIO®) is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab 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, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.7-9 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.9-11 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Approved Indications in the US
In the US, the FDA granted accelerated approval for avelumab (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 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
Important Safety Information from the US FDA-Approved Label
The warnings and precautions for BAVENCIO® include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab for mMCC and patients with locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
References
1. American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-special-section-ovarian-cancer-2018.pdf. Accessed December 2018.
2. Ledermann, JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (Supplement 6): vi24–vi32, doi:10.1093/annonc/mdt333.
3. Ozol, RJ. Challenges for chemotherapy in ovarian cancer. Annals of Oncology 2006;17(5):v181-187.
4. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project. Available at: https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed December 2018.
5. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project. Available at: https://www.wcrf.org/dietandcancer/ovarian-cancer. Accessed December 2018.
6. American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed December 2018.
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.
9. 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.
10. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
11. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.
SOURCE: Merck KGaA
Post Views: 24
