81% overall response rate and 40% complete response rate by investigator assessment with consistent results observed across several pre-specified subgroups of patients
WILMINGTON, DE, USA I December 9, 2017 I AstraZeneca and Acerta Pharma, its hematology research and development center of excellence, today presented results from the open-label, single-arm Phase II ACE-LY-004 clinical trial, which served as the basis for the recent US Food and Drug Administration (FDA) accelerated approval of CALQUENCE® (acalabrutinib). The findings were presented for the first time during an oral session at the 59th American Society of Hematology (ASH) Annual Meeting & Exhibition in Atlanta and demonstrate the safety profile and efficacy of CALQUENCE in the management of previously-treated mantle cell lymphoma (MCL).
CALQUENCE was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. This indication is approved based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “These results presented for the first time to the medical community highlight the potential of CALQUENCE as a treatment for people with relapsed or refractory mantle cell lymphoma, a life-threatening form of blood cancer. These data reinforce the important progress of our clinical development program as well as our commitment to advancing the treatment of patients with blood cancers.”
Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL clinical trial, said: “Most people living with mantle cell lymphoma will unfortunately relapse, and new treatment options are greatly needed. As shown by the consistent overall response rates observed in this trial across several pre-specified subgroups, acalabrutinib is a welcome new treatment option for certain patients with this aggressive blood cancer.”
Summary of key investigator-assessed efficacy results from ACE-LY-004, a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL (15.2 months median follow-up):
| |
|
|
|
|
| Efficacy measure |
|
|
|
Patients (percent response) |
|
Overall response rate
(Complete response + partial response)
Complete response
Partial response
|
|
|
|
81% (95% CI: 73,87)
40% (95% CI: 31,49)
41% (95% CI: 32,50)
|
| Stable disease |
|
|
|
9% (95% CI: 5,15) |
| Progressive disease |
|
|
|
8% (95% CI: 4,14) |
| Not evaluable |
|
|
|
2% (95% CI: 1,7) |
Per 2014 Lugano classification response criteria for non-Hodgkin lymphoma; high concordance was observed between investigator-assessed and independent review committee assessed overall response and complete response rates, respectively.
The overall response rate was consistent across multiple subgroups including age, tumor burden and number or type of prior treatments. The secondary endpoint of median duration of response had not yet been reached at 15.2 months median follow-up. The median time-to-response, an exploratory endpoint, was 1.9 months. After 12 months of treatment, 72% (95% CI: 62,80) of patients were still responding to acalabrutinib treatment. The secondary endpoints of progression-free survival and overall survival had not yet been reached; at 12 months, the progression-free survival and overall survival rates were 67% (95% CI: 58,75) and 87% (95% CI: 79,92), respectively.
In this trial, the most common non-hematological adverse reactions (reported in ≥20% of patients at a median follow-up time of 15.2 months) were headache (38%), diarrhea (30%), fatigue (26%) and myalgia (21%), per investigator assessment. Grade 3 or 4 adverse reactions (≥5%) included anemia (12%), neutropenia (11%), and pneumonia (6%). Please refer to the Important Safety Information about CALQUENCE (acalabrutinib) below for the adverse reaction rates as shown in the FDA-approved product label.
A Grade 3 gastrointestinal hemorrhage occurred in 1 patient (1%) with a history of a gastrointestinal ulcer. Tumor lysis syndrome was reported in 2 patients (2%). A Grade 5 adverse reaction of aortic stenosis was reported in 1 patient with previous history and was not considered related to study treatment.
Treatment discontinuation was primarily due to progressive disease (31%) or adverse reaction (6%).
About CALQUENCE (acalabrutinib)
CALQUENCE® (acalabrutinib; previously known as ACP-196) is an inhibitor of Bruton tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity. In B cells, BTK signaling results in activation of pathways necessary for B cell proliferation, trafficking, chemotaxis and adhesion.
CALQUENCE was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. CALQUENCE is not approved for use outside of its labeled indication in the US.
The recommended dose of CALQUENCE is one 100mg capsule taken orally approximately every twelve hours until disease progression or unacceptable toxicity. CALQUENCE may be taken with or without food.
CALQUENCE is also in development for the treatment of multiple B-cell malignancies and other cancers including 1st line MCL, chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. It is also being developed as a monotherapy and in combination trials for solid tumors. More than 35 clinical trials across 40 countries with more than 2,500 patients are underway or have been completed.
CALQUENCE was granted Orphan Drug Designation for the treatment of patients with CLL, MCL and WM in 2015, and Breakthrough Therapy Designation in August 2017 by the US FDA for the treatment of patients with MCL who have received at least one prior therapy.
About Mantle Cell Lymphoma (MCL)
MCL is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. MCL accounts for approximately 3% of new NHL cases in the US, with approximately 3,300 new cases of MCL diagnosed each year. The median age at diagnosis is 68 years, with a 3:1 male predominance. While MCL patients initially respond to treatment, there is a high relapse rate.
About the ACE-LY-004 Trial
ACE-LY-004 is a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL. The trial showed that 81% (95% CI: 73,87) of patients treated with CALQUENCE achieved an overall response; 40% (95% CI: 31,49) achieved a complete response and 41% (95% CI: 32,50) achieved a partial response, per 2014 Lugano classification as assessed by investigator.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that have the potential to transform patients’ lives and the Company’s future. With at least six new medicines aimed to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms 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 Acerta Pharma
Acerta Pharma, a member of the AstraZeneca Group, is creating novel therapies intended for the treatment of cancer and autoimmune diseases. AstraZeneca acquired a majority stake interest in Acerta Pharma, which serves as AstraZeneca’s hematology research and development center of excellence. For more information, please visit www.acerta-pharma.com.
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 therapy areas – Oncology, Cardiovascular & Metabolic Diseases 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.
SOURCE: AstraZeneca
Post Views: 74
81% overall response rate and 40% complete response rate by investigator assessment with consistent results observed across several pre-specified subgroups of patients
WILMINGTON, DE, USA I December 9, 2017 I AstraZeneca and Acerta Pharma, its hematology research and development center of excellence, today presented results from the open-label, single-arm Phase II ACE-LY-004 clinical trial, which served as the basis for the recent US Food and Drug Administration (FDA) accelerated approval of CALQUENCE® (acalabrutinib). The findings were presented for the first time during an oral session at the 59th American Society of Hematology (ASH) Annual Meeting & Exhibition in Atlanta and demonstrate the safety profile and efficacy of CALQUENCE in the management of previously-treated mantle cell lymphoma (MCL).
CALQUENCE was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. This indication is approved based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “These results presented for the first time to the medical community highlight the potential of CALQUENCE as a treatment for people with relapsed or refractory mantle cell lymphoma, a life-threatening form of blood cancer. These data reinforce the important progress of our clinical development program as well as our commitment to advancing the treatment of patients with blood cancers.”
Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL clinical trial, said: “Most people living with mantle cell lymphoma will unfortunately relapse, and new treatment options are greatly needed. As shown by the consistent overall response rates observed in this trial across several pre-specified subgroups, acalabrutinib is a welcome new treatment option for certain patients with this aggressive blood cancer.”
Summary of key investigator-assessed efficacy results from ACE-LY-004, a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL (15.2 months median follow-up):
| |
|
|
|
|
| Efficacy measure |
|
|
|
Patients (percent response) |
|
Overall response rate
(Complete response + partial response)
Complete response
Partial response
|
|
|
|
81% (95% CI: 73,87)
40% (95% CI: 31,49)
41% (95% CI: 32,50)
|
| Stable disease |
|
|
|
9% (95% CI: 5,15) |
| Progressive disease |
|
|
|
8% (95% CI: 4,14) |
| Not evaluable |
|
|
|
2% (95% CI: 1,7) |
Per 2014 Lugano classification response criteria for non-Hodgkin lymphoma; high concordance was observed between investigator-assessed and independent review committee assessed overall response and complete response rates, respectively.
The overall response rate was consistent across multiple subgroups including age, tumor burden and number or type of prior treatments. The secondary endpoint of median duration of response had not yet been reached at 15.2 months median follow-up. The median time-to-response, an exploratory endpoint, was 1.9 months. After 12 months of treatment, 72% (95% CI: 62,80) of patients were still responding to acalabrutinib treatment. The secondary endpoints of progression-free survival and overall survival had not yet been reached; at 12 months, the progression-free survival and overall survival rates were 67% (95% CI: 58,75) and 87% (95% CI: 79,92), respectively.
In this trial, the most common non-hematological adverse reactions (reported in ≥20% of patients at a median follow-up time of 15.2 months) were headache (38%), diarrhea (30%), fatigue (26%) and myalgia (21%), per investigator assessment. Grade 3 or 4 adverse reactions (≥5%) included anemia (12%), neutropenia (11%), and pneumonia (6%). Please refer to the Important Safety Information about CALQUENCE (acalabrutinib) below for the adverse reaction rates as shown in the FDA-approved product label.
A Grade 3 gastrointestinal hemorrhage occurred in 1 patient (1%) with a history of a gastrointestinal ulcer. Tumor lysis syndrome was reported in 2 patients (2%). A Grade 5 adverse reaction of aortic stenosis was reported in 1 patient with previous history and was not considered related to study treatment.
Treatment discontinuation was primarily due to progressive disease (31%) or adverse reaction (6%).
About CALQUENCE (acalabrutinib)
CALQUENCE® (acalabrutinib; previously known as ACP-196) is an inhibitor of Bruton tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity. In B cells, BTK signaling results in activation of pathways necessary for B cell proliferation, trafficking, chemotaxis and adhesion.
CALQUENCE was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. CALQUENCE is not approved for use outside of its labeled indication in the US.
The recommended dose of CALQUENCE is one 100mg capsule taken orally approximately every twelve hours until disease progression or unacceptable toxicity. CALQUENCE may be taken with or without food.
CALQUENCE is also in development for the treatment of multiple B-cell malignancies and other cancers including 1st line MCL, chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. It is also being developed as a monotherapy and in combination trials for solid tumors. More than 35 clinical trials across 40 countries with more than 2,500 patients are underway or have been completed.
CALQUENCE was granted Orphan Drug Designation for the treatment of patients with CLL, MCL and WM in 2015, and Breakthrough Therapy Designation in August 2017 by the US FDA for the treatment of patients with MCL who have received at least one prior therapy.
About Mantle Cell Lymphoma (MCL)
MCL is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. MCL accounts for approximately 3% of new NHL cases in the US, with approximately 3,300 new cases of MCL diagnosed each year. The median age at diagnosis is 68 years, with a 3:1 male predominance. While MCL patients initially respond to treatment, there is a high relapse rate.
About the ACE-LY-004 Trial
ACE-LY-004 is a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL. The trial showed that 81% (95% CI: 73,87) of patients treated with CALQUENCE achieved an overall response; 40% (95% CI: 31,49) achieved a complete response and 41% (95% CI: 32,50) achieved a partial response, per 2014 Lugano classification as assessed by investigator.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that have the potential to transform patients’ lives and the Company’s future. With at least six new medicines aimed to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms 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 Acerta Pharma
Acerta Pharma, a member of the AstraZeneca Group, is creating novel therapies intended for the treatment of cancer and autoimmune diseases. AstraZeneca acquired a majority stake interest in Acerta Pharma, which serves as AstraZeneca’s hematology research and development center of excellence. For more information, please visit www.acerta-pharma.com.
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 therapy areas – Oncology, Cardiovascular & Metabolic Diseases 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.
SOURCE: AstraZeneca
Post Views: 74
