Phase 3 Results Published in The Journal of The American Medical Association
93% of Patients With Minimal Residual Disease (MRD) at Baseline Achieved MRD Negative Remission With BLINCYTO Versus 24% After Chemotherapy
THOUSAND OAKS, CA, USA I March 2, 2021 I Amgen (NASDAQ:AMGN) today announced that data from a multicenter, randomized Phase 3 study evaluating the efficacy, safety and tolerability of BLINCYTO® (blinatumomab) compared with consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric patients with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia (B-ALL) were published in The Journal of the American Medical Association (JAMA).1
BLINCYTO demonstrated significantly prolonged event-free survival (events were defined by relapse, death, second malignancy, or failure to achieve complete remission) compared with chemotherapy. After a median of 22.4 months follow-up, 69% of patients treated with BLINCYTO were alive and event-free compared with 43% of patients treated with chemotherapy. Additionally, following treatment with BLINCYTO, 93% of patients with MRD at baseline achieved MRD negative remission compared with 24% of patients treated with chemotherapy. The 36-month overall survival (OS) estimate in the BLINCYTO group was 81.1% versus 55.8% in the chemotherapy group, and the median OS has not been met.
“Acute lymphoblastic leukemia is the most common type of cancer in children. Unfortunately, approximately 15% of children with high-risk B-ALL relapse after frontline chemotherapy,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “There remains an urgent need for novel treatment options for these patients, and the study results support BLINCYTO as a new standard of care consolidation therapy for patients with this aggressive disease.”
In the BLINCYTO group versus the chemotherapy group, the incidence of serious adverse events (AEs) was 24.1% vs. 43.1%, respectively, and the incidence of adverse events of grade 3 or higher was 57.4% vs. 82.4% respectively. No fatal adverse events were reported. The most common adverse events (AEs) in the BLINCYTO treatment arm were pyrexia (81.5%), nausea (40.7%), headache (35.2%), stomatitis (35.2%) and vomiting (29.6%).
“I am thrilled the study results demonstrated that BLINCYTO was more effective and associated with fewer and less severe toxicities compared to intensive chemotherapy,” said study investigator, Franco Locatelli, M.D., PhD, Sapienza, University of Rome, Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Rome. “Chemotherapy has been used as primary consolidation treatment for ALL patients before receiving a stem cell transplant, despite this approach being only partially effective and associated with relevant toxicity. BLINCYTO has now been shown to be a more effective and safer consolidation therapy option for children with high-risk first-relapse B-ALL.”
Results from the Children’s Oncology Group (COG) Phase 3 study (AALL1331) evaluating BLINCYTO in children, adolescents, and young adults with first-relapse B-ALL have also been published today in JAMA.2 In both studies, treatment with BLINCYTO resulted in less severe toxicities and higher rates of MRD remission.
BLINCYTO, a bispecific CD19-directed CD3 T cell BiTE® (bispecific T cell engager) molecule, is the first approved molecule from Amgen’s BiTE immuno-oncology platform, and the first and only therapy to receive regulatory approval globally for the treatment of MRD-positive B-cell precursor ALL.
About the 20120215 Study
Study 20120215 is a Phase 3 open-label, multicenter, randomized, controlled trial evaluating event-free survival after treatment with BLINCYTO compared with standard of care consolidation chemotherapy in pediatric patients with high-risk first-relapse B-cell ALL. Study enrollment was terminated early in September 2019 due to encouraging efficacy in the BLINCYTO arm and was based on a recommendation from the Independent Data Monitoring Committee (DMC) in accordance with a prespecified stopping rule. Key secondary endpoints included overall survival and MRD response, AEs, 100-day mortality after alloHSCT, incidence of anti-blinatumomab antibody formation, cumulative incidence of relapse. This is a global study that is being conducted as part of the PIP (Pediatric Investigation Plan) agreed to between Amgen and the EMA and is being conducted in Australia and various countries in the EU and Latin America. Click here to read about the trial on ClinicalTrials.gov.
About the COG AALL1331 Study
The COG AALL1331 study is a risk-stratified, randomized, Phase 3 trial of blinatumomab in first relapse of pediatric B-ALL to evaluate disease-free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapsed B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab. It also compares the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab. Key secondary endpoints include overall survival of HR, IR, and LR relapsed B-ALL patients. This is a global study that is being conducted in Australia, Canada, New Zealand and the United States. Click here to read about the trial on ClinicalTrials.gov. AALL1331 is supported by the National Cancer Institute (NCI), part of the National Institutes of Health under award number NCTN Operations Center Grant U10CA 180886 to COG. The study is sponsored by NCI and designed and conducted by the NCI-funded COG. Amgen provided BLINCYTO for AALL1331 under a Cooperative Research and Development Agreement between the NCI and Amgen.
About The Children’s Oncology Group (COG)
COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 14,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG’s mission is to improve the cure rate and outcomes for all children with cancer.
About BiTE® Technology
BiTE® (bispecific T cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit www.AmgenBiTETechnology.com.
About BLINCYTO® (Blinatumomab)
BLINCYTO is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body’s immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.
BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:
- relapsed or refractory B-cell precursor ALL in adults and children.
- B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children.This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:
- adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL).
- adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
- paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation
Please see full Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.
About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.
At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.
To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. For more information, follow us on www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References
- Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. Published March 2, 2021. doi: 10.1001/jama.2021.0987
- Brown PA, Ji L, Xu X, et al. Effect of postreinduction consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. Published March 2, 2021. doi:10.1001/jama.2021.0669
SOURCE: Amgen
Post Views: 91
Phase 3 Results Published in The Journal of The American Medical Association
93% of Patients With Minimal Residual Disease (MRD) at Baseline Achieved MRD Negative Remission With BLINCYTO Versus 24% After Chemotherapy
THOUSAND OAKS, CA, USA I March 2, 2021 I Amgen (NASDAQ:AMGN) today announced that data from a multicenter, randomized Phase 3 study evaluating the efficacy, safety and tolerability of BLINCYTO® (blinatumomab) compared with consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric patients with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia (B-ALL) were published in The Journal of the American Medical Association (JAMA).1
BLINCYTO demonstrated significantly prolonged event-free survival (events were defined by relapse, death, second malignancy, or failure to achieve complete remission) compared with chemotherapy. After a median of 22.4 months follow-up, 69% of patients treated with BLINCYTO were alive and event-free compared with 43% of patients treated with chemotherapy. Additionally, following treatment with BLINCYTO, 93% of patients with MRD at baseline achieved MRD negative remission compared with 24% of patients treated with chemotherapy. The 36-month overall survival (OS) estimate in the BLINCYTO group was 81.1% versus 55.8% in the chemotherapy group, and the median OS has not been met.
“Acute lymphoblastic leukemia is the most common type of cancer in children. Unfortunately, approximately 15% of children with high-risk B-ALL relapse after frontline chemotherapy,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “There remains an urgent need for novel treatment options for these patients, and the study results support BLINCYTO as a new standard of care consolidation therapy for patients with this aggressive disease.”
In the BLINCYTO group versus the chemotherapy group, the incidence of serious adverse events (AEs) was 24.1% vs. 43.1%, respectively, and the incidence of adverse events of grade 3 or higher was 57.4% vs. 82.4% respectively. No fatal adverse events were reported. The most common adverse events (AEs) in the BLINCYTO treatment arm were pyrexia (81.5%), nausea (40.7%), headache (35.2%), stomatitis (35.2%) and vomiting (29.6%).
“I am thrilled the study results demonstrated that BLINCYTO was more effective and associated with fewer and less severe toxicities compared to intensive chemotherapy,” said study investigator, Franco Locatelli, M.D., PhD, Sapienza, University of Rome, Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Rome. “Chemotherapy has been used as primary consolidation treatment for ALL patients before receiving a stem cell transplant, despite this approach being only partially effective and associated with relevant toxicity. BLINCYTO has now been shown to be a more effective and safer consolidation therapy option for children with high-risk first-relapse B-ALL.”
Results from the Children’s Oncology Group (COG) Phase 3 study (AALL1331) evaluating BLINCYTO in children, adolescents, and young adults with first-relapse B-ALL have also been published today in JAMA.2 In both studies, treatment with BLINCYTO resulted in less severe toxicities and higher rates of MRD remission.
BLINCYTO, a bispecific CD19-directed CD3 T cell BiTE® (bispecific T cell engager) molecule, is the first approved molecule from Amgen’s BiTE immuno-oncology platform, and the first and only therapy to receive regulatory approval globally for the treatment of MRD-positive B-cell precursor ALL.
About the 20120215 Study
Study 20120215 is a Phase 3 open-label, multicenter, randomized, controlled trial evaluating event-free survival after treatment with BLINCYTO compared with standard of care consolidation chemotherapy in pediatric patients with high-risk first-relapse B-cell ALL. Study enrollment was terminated early in September 2019 due to encouraging efficacy in the BLINCYTO arm and was based on a recommendation from the Independent Data Monitoring Committee (DMC) in accordance with a prespecified stopping rule. Key secondary endpoints included overall survival and MRD response, AEs, 100-day mortality after alloHSCT, incidence of anti-blinatumomab antibody formation, cumulative incidence of relapse. This is a global study that is being conducted as part of the PIP (Pediatric Investigation Plan) agreed to between Amgen and the EMA and is being conducted in Australia and various countries in the EU and Latin America. Click here to read about the trial on ClinicalTrials.gov.
About the COG AALL1331 Study
The COG AALL1331 study is a risk-stratified, randomized, Phase 3 trial of blinatumomab in first relapse of pediatric B-ALL to evaluate disease-free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapsed B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab. It also compares the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab. Key secondary endpoints include overall survival of HR, IR, and LR relapsed B-ALL patients. This is a global study that is being conducted in Australia, Canada, New Zealand and the United States. Click here to read about the trial on ClinicalTrials.gov. AALL1331 is supported by the National Cancer Institute (NCI), part of the National Institutes of Health under award number NCTN Operations Center Grant U10CA 180886 to COG. The study is sponsored by NCI and designed and conducted by the NCI-funded COG. Amgen provided BLINCYTO for AALL1331 under a Cooperative Research and Development Agreement between the NCI and Amgen.
About The Children’s Oncology Group (COG)
COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 14,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG’s mission is to improve the cure rate and outcomes for all children with cancer.
About BiTE® Technology
BiTE® (bispecific T cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit www.AmgenBiTETechnology.com.
About BLINCYTO® (Blinatumomab)
BLINCYTO is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body’s immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.
BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:
- relapsed or refractory B-cell precursor ALL in adults and children.
- B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children.This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:
- adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL).
- adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
- paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation
Please see full Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.
About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.
At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.
To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. For more information, follow us on www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References
- Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. Published March 2, 2021. doi: 10.1001/jama.2021.0987
- Brown PA, Ji L, Xu X, et al. Effect of postreinduction consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. Published March 2, 2021. doi:10.1001/jama.2021.0669
SOURCE: Amgen
Post Views: 91
