AstraZeneca and Merck’s LYNPARZA when added to standard-of-care bevacizumab significantly increased the time women lived without disease progression or death
WILMINGTON, DE, USA I August 14, 2019 I AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the U.S. and Canada) today announced positive results from the Phase III PAOLA-1 trial in women with advanced ovarian cancer. The trial, in the 1st-line maintenance setting, compared LYNPARZA® (olaparib) added to standard-of-care (SoC) bevacizumab vs. bevacizumab alone in women with or without BRCA gene mutations.
The trial met its primary endpoint in the intent-to-treat (ITT) population with a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS), increasing the time women taking LYNPARZA plus bevacizumab lived without disease progression or death vs. those taking bevacizumab alone. The results, including biomarker sub-group analyses, will be presented at a forthcoming medical meeting. The safety and tolerability profiles observed in PAOLA-1 were generally consistent with those known for each medicine. PAOLA-1 is the second positive Phase III trial with LYNPARZA in 1st-line advanced ovarian cancer.
José Baselga, Executive Vice President, Oncology R&D, said: “The positive results from the PAOLA-1 trial demonstrate a clear potential benefit of adding LYNPARZA to the standard treatment bevacizumab for women with advanced ovarian cancer. Following positive results from the SOLO-1 trial for women with a BRCA gene mutation, the PAOLA-1 trial marks yet another positive Phase III trial for LYNPARZA as a 1st-line maintenance treatment for women with advanced ovarian cancer. We look forward to discussing the results with global health authorities as soon as possible.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: “The Phase III PAOLA-1 trial demonstrates Merck and AstraZeneca’s continued commitment to improving clinical outcomes for women with advanced ovarian cancer. In this co-operative group trial sponsored by ARCAGY Research, maintenance treatment with LYNPARZA when added to a standard-of-care treatment was evaluated in an environment representative of real clinical practice. By studying LYNPARZA in this broader patient population, we have learned more about how it might be able to help even more patients with advanced ovarian cancer in the future.”
Eric Pujade-Lauraine, Medical Director of ARCAGY Research, said: “The PAOLA-1 trial is a positive example of the strength and promise of academia-industry collaboration in advancing science and new treatment options for patients. We greatly appreciate the commitment of AstraZeneca and Merck in working with academic cooperative groups in ENGOT and look forward to sharing the full PAOLA-1 results at a forthcoming medical meeting.”
PAOLA-1 is an ENGOT (European Network for Gynecological Trial) trial, sponsored by ARCAGY Research (Association de Recherche sur les Cancers dont Gynecologiques) and GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specialized in clinical and translational research in women’s cancers and a member of the GCIG (Gynecologic Cancer InterGroup).
LYNPARZA is currently approved as first-line maintenance treatment in BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is also approved for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy. For first-line maintenance in advanced ovarian cancer and the metastatic breast cancer setting, physicians should select patients for therapy based on an FDA-approved companion diagnostic.
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Maintenance Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.
Advanced gBRCAm Ovarian Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer
In patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Please see complete Prescribing Information, including Patient Information (Medication Guide).
NOTES TO EDITORS
About PAOLA-1
PAOLA-1 is a randomized, double-blind Phase III trial evaluating the efficacy and safety of LYNPARZA (300 mg twice daily) when added to SoC bevacizumab vs. bevacizumab alone, as a 1st-line maintenance treatment of advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. The ITT (intent to treat) population refers to all patients enrolled in the trial.
About LYNPARZA
LYNPARZA® (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is being tested in a range of DDR-deficient tumor types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.
About ovarian cancer
Approximately 22,000 women in the United States are diagnosed with ovarian cancer (including ovarian, fallopian tube and primary peritoneal cancers) each year. Among women in the United States, it is the ninth most common cancer and the fifth leading cause of cancer death. The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations.
AstraZeneca is committed to the continued development of our R&D portfolio for ovarian cancer, with a focus on improved care for all patients.
About BRCA Mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
SOURCE: AstraZeneca
Post Views: 21
AstraZeneca and Merck’s LYNPARZA when added to standard-of-care bevacizumab significantly increased the time women lived without disease progression or death
WILMINGTON, DE, USA I August 14, 2019 I AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the U.S. and Canada) today announced positive results from the Phase III PAOLA-1 trial in women with advanced ovarian cancer. The trial, in the 1st-line maintenance setting, compared LYNPARZA® (olaparib) added to standard-of-care (SoC) bevacizumab vs. bevacizumab alone in women with or without BRCA gene mutations.
The trial met its primary endpoint in the intent-to-treat (ITT) population with a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS), increasing the time women taking LYNPARZA plus bevacizumab lived without disease progression or death vs. those taking bevacizumab alone. The results, including biomarker sub-group analyses, will be presented at a forthcoming medical meeting. The safety and tolerability profiles observed in PAOLA-1 were generally consistent with those known for each medicine. PAOLA-1 is the second positive Phase III trial with LYNPARZA in 1st-line advanced ovarian cancer.
José Baselga, Executive Vice President, Oncology R&D, said: “The positive results from the PAOLA-1 trial demonstrate a clear potential benefit of adding LYNPARZA to the standard treatment bevacizumab for women with advanced ovarian cancer. Following positive results from the SOLO-1 trial for women with a BRCA gene mutation, the PAOLA-1 trial marks yet another positive Phase III trial for LYNPARZA as a 1st-line maintenance treatment for women with advanced ovarian cancer. We look forward to discussing the results with global health authorities as soon as possible.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: “The Phase III PAOLA-1 trial demonstrates Merck and AstraZeneca’s continued commitment to improving clinical outcomes for women with advanced ovarian cancer. In this co-operative group trial sponsored by ARCAGY Research, maintenance treatment with LYNPARZA when added to a standard-of-care treatment was evaluated in an environment representative of real clinical practice. By studying LYNPARZA in this broader patient population, we have learned more about how it might be able to help even more patients with advanced ovarian cancer in the future.”
Eric Pujade-Lauraine, Medical Director of ARCAGY Research, said: “The PAOLA-1 trial is a positive example of the strength and promise of academia-industry collaboration in advancing science and new treatment options for patients. We greatly appreciate the commitment of AstraZeneca and Merck in working with academic cooperative groups in ENGOT and look forward to sharing the full PAOLA-1 results at a forthcoming medical meeting.”
PAOLA-1 is an ENGOT (European Network for Gynecological Trial) trial, sponsored by ARCAGY Research (Association de Recherche sur les Cancers dont Gynecologiques) and GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specialized in clinical and translational research in women’s cancers and a member of the GCIG (Gynecologic Cancer InterGroup).
LYNPARZA is currently approved as first-line maintenance treatment in BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is also approved for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy. For first-line maintenance in advanced ovarian cancer and the metastatic breast cancer setting, physicians should select patients for therapy based on an FDA-approved companion diagnostic.
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Maintenance Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.
Advanced gBRCAm Ovarian Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer
In patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Please see complete Prescribing Information, including Patient Information (Medication Guide).
NOTES TO EDITORS
About PAOLA-1
PAOLA-1 is a randomized, double-blind Phase III trial evaluating the efficacy and safety of LYNPARZA (300 mg twice daily) when added to SoC bevacizumab vs. bevacizumab alone, as a 1st-line maintenance treatment of advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. The ITT (intent to treat) population refers to all patients enrolled in the trial.
About LYNPARZA
LYNPARZA® (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is being tested in a range of DDR-deficient tumor types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.
About ovarian cancer
Approximately 22,000 women in the United States are diagnosed with ovarian cancer (including ovarian, fallopian tube and primary peritoneal cancers) each year. Among women in the United States, it is the ninth most common cancer and the fifth leading cause of cancer death. The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations.
AstraZeneca is committed to the continued development of our R&D portfolio for ovarian cancer, with a focus on improved care for all patients.
About BRCA Mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
SOURCE: AstraZeneca
Post Views: 21
