Calquence approved in the US for adult patients with chronic lymphocytic leukaemia | Small Molecules | News Channels – PipelineReview.com
Posted: November 23, 2019 at 8:45 am
DetailsCategory: Small MoleculesPublished on Friday, 22 November 2019 14:04Hits: 302
Two Phase III Calquence trials demonstrated superior progression-free survival across multiple settings while maintaining favourable tolerability
Calquence combined with obinutuzumab and as monotherapy reducedthe risk of disease progression or death by 90% and 80%, respectively in ELEVATE-TN
LONDON, UK I November 21, 2019 I AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved Calquence (acalabrutinib) for adult patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).1 The US approval was granted under the FDAs Real-Time Oncology Review and newly established Project Orbis programmes.
The approval is based on positive results from the interim analyses of two Phase III clinical trials, ELEVATE-TN in patients with previously untreated CLL and ASCEND in patients with relapsed or refractory CLL. Together, the trials showed that Calquence in combination with obinutuzumab or as a monotherapy significantly reduced the relative risk of disease progression or death versus the comparator arms in both 1st-line and relapsed or refractory CLL. Across both trials, the safety and tolerability of Calquence were consistent with its established profile.1
Dave Fredrickson, Executive Vice President, Oncology Business Unit said: With over 20,000 new cases anticipated this year in the US alone, todays approval of Calquence provides new hope for patients with one of the most common types of adult leukaemia, offering outstanding efficacy and a favourable tolerability profile. The chronic lymphocytic leukaemia patient population is known to face multiple comorbidities, and tolerability is a critical factor in their treatment.
Dr Jeff Sharman, Director of Research at Willamette Valley Cancer Institute, Medical Director of Hematology Research for The US Oncology Network, and a lead author of the ELEVATE-TN trial, said: Tolerability remains an issue in the current treatment landscape of chronic lymphocytic leukaemia, which may require ongoing therapy for many years. In the ELEVATE-TN and ASCEND trials comparing Calquence to commonly used treatment regimens, Calquence demonstrated a clinically meaningful improvement in progression-free survival in patients across multiple settings, while maintaining its favourable tolerability and safety profile.
The results of the interim analysis of the ELEVATE-TN trial will be presented at the upcoming American Society of Hematology congress.2
The trial showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with either Calquence in combination with obinutuzumab or Calquence monotherapy versus chlorambucil chemotherapy plus obinutuzumab, a current standard-of-care combination used in the control arm.1
In the Calquence combination arm, risk of disease progression or death was reduced by 90% (HR 0.10; 95% CI, 0.06-0.17, p<0.0001) and in the monotherapy arm it was reduced by 80% (HR 0.20; 95% CI, 0.13-0.30, p<0.0001).1
The median time to disease progression for patients treated with Calquence in combination with obinutuzumab or as a monotherapy has not yet been reached versus 22.6 months (95% CI, 20-28) for chlorambucil plus obinutuzumab.1
ELEVATE-TN safety overview (most common ARs, 15%):1
Includes multiple ADR terms.
In patients treated with the combination of Calquence plus obinutuzumab, adverse reactions (ARs) led to treatment discontinuation in 11% of patients and a dose reduction of Calquence in 7% of patients. In the monotherapy arm, ARs led to discontinuation in 10% and dose reduction in 4% of patients.1 In the control arm, ARs led to regimen discontinuation in 14% of patients with a dose reduction of chlorambucil in 28% of patients.3 There were no dose reductions for obinutuzumab.1,3
In 1,029 patients with haematologic malignancies who were treated with Calquence 100mg approximately every 12 hours across multiple clinical trials, where 88% received treatment for at least six months and 79% received treatment for at least one year, serious or Grade 3 infections occurred in 19%, and Grade 3 atrial fibrillation and flutter occurred in 1.1% of patients.In the same patient population, major haemorrhage occurred in 3.0% (serious or Grade 3 bleeding or any central nervous system bleeding), with fatal haemorrhage occurring in 0.1% of patients. Second primary malignancies (all grades) including skin cancers occurred in 12% of patients.1
The US approval is among the first to be granted under Project Orbis, an initiative of the US FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review. 4
About Calquence
In the US, Calquence (acalabrutinib) is indicated for the treatment of adult patients with chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL). In the US, Canada, Australia, Brazil, Qatar, the United Arab Emirates, Mexico, Argentina, Singapore, Chile, and recently India, Calquence is indicated for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Approved under accelerated review in the US, continued approval for previously treated MCL is contingent upon verification and confirmation of clinical benefit in confirmatory trials.
Calquence is a next-generation selective inhibitor of Brutons tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.1,5,6,7 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.1
As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 23 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrm macroglobulinaemia and follicular lymphoma and other haematologic malignancies. Several Phase III clinical trials in CLL are ongoing, including ASCEND, ELEVATE-TN, ELEVATE-RR (ACE-CL-006) evaluating Calquence versus ibrutinib in patients with previously treated high-risk CLL, and ACE-CL-311 evaluating Calquence in combination with venetoclax and with/without obinutuzumab versus chemoimmunotherapy in patients with previously untreated CLL without 17p deletion or TP53 mutation.
About ELEVATE-TN
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy ofCalquence in combination with obinutuzumab, a CD20 monoclonal antibody, or Calquence alone versus chlorambucil, a chemotherapy, in combination with obinutuzumab in previously untreated patients with CLL. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg twice daily until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity).1,8
The primary endpoint is PFS in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment and overall survival.1,8
About ASCEND
ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in previously treated patients with CLL. In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received investigators choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3K inhibitor, or rituximab in combination with bendamustine, a chemotherapy.1,9
The primary endpoint is PFS assessed by an IRC, and key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as overall survival, patient-reported outcomes and time to next treatment.1,9
About CLL
Chronic lymphocytic leukaemia (CLL) is one of the most common types of leukaemia in adults, with an estimated 105,000 new cases globally each year and 20,720 new cases in the US in 2019, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.10,11,12,13 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.10 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.10 This could result in anaemia, infection and bleeding.10 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
About AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Companys haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZenecas haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.
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 Companys 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, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZenecas main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates and by championing the development of personalised 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 commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal and Metabolism, and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
References
1. CALQUENCE (acalabrutinib) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
2. Sharman JP, et al. ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL). Abstract 31 at: American Society of Hematology 2019 Annual Meeting and Exposition. Available online. Accessed November 2019.
3. Data on File. REF-64711. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
4. US Food and Drug Administration. Project Orbis. Available online. Accessed November 2019.
5. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
6. Khan Y & OBrien S. Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. Future Oncol. 2018;15(6).
7. Byrd JC, et al. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016; 374:323-332.
8. ClinicalTrials.gov. Elevate CLL TN: Study of Obinutuzumab + Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL. NCT02475681. Available online. Accessed November 2019.
9. ClinicalTrials.gov. A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL. NCT02970318. Available online. Accessed November 2019.
10. National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)Patient Version. Available online. Accessed November 2019.
11. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016. JAMA Oncol. 2018;4(11):1553-1568.
12. American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Available online. Accessed November 2019.
13. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126:871.
SOURCE: AstraZeneca
See the article here:
Calquence approved in the US for adult patients with chronic lymphocytic leukaemia | Small Molecules | News Channels - PipelineReview.com
- Secret History of Diamonds Narrated for the Visually Impaired - Part 2 of 4 [Last Updated On: June 24th, 2011] [Originally Added On: June 24th, 2011]
- Skin Stem Cells: Their Biology [Last Updated On: June 24th, 2011] [Originally Added On: June 24th, 2011]
- Emerge Labs New Anti Aging Swiss Apple Stem Cell Skin Care [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- No Avastin for Breast Cancer [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- Signals Skincare System [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- Signals Skincare System [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- Growing Nerve Cells [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- Elaine Fuchs Part 2: Tapping the Potential of Adult Stem Cells, and Summary [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- A Major Breakthrough in Skin Care and Nutrition [Last Updated On: June 27th, 2011] [Originally Added On: June 27th, 2011]
- Stem Cell Facial At Metamorphosis Day Spa Using Emerge Labs Skin Care [Last Updated On: June 27th, 2011] [Originally Added On: June 27th, 2011]
- Come Back Kid [Last Updated On: June 28th, 2011] [Originally Added On: June 28th, 2011]
- PhytoCell.mp4 [Last Updated On: June 28th, 2011] [Originally Added On: June 28th, 2011]
- When Beauty Calls: The Link between Science and Skin Care [Last Updated On: June 29th, 2011] [Originally Added On: June 29th, 2011]
- Skin Stem Cells: Their Biology [Last Updated On: June 29th, 2011] [Originally Added On: June 29th, 2011]
- Come Back Kid [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- PhytoCell.mp4 [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- The Skin Gun stem cell research [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- World's 1st Nutricosmetic with Stem Cell Nutrients [Last Updated On: July 2nd, 2011] [Originally Added On: July 2nd, 2011]
- NG Raccoon Attack [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- No Avastin for Breast Cancer [Last Updated On: July 4th, 2011] [Originally Added On: July 4th, 2011]
- E'shee HBA Global Expo 2011, NYC. Skin Care Anti-Aging Symposium [Last Updated On: July 5th, 2011] [Originally Added On: July 5th, 2011]
- Growing Nerve Cells [Last Updated On: July 9th, 2011] [Originally Added On: July 9th, 2011]
- The Skin Gun [Last Updated On: July 9th, 2011] [Originally Added On: July 9th, 2011]
- E'shee HBA Global Expo 2011, NYC. Skin Care Anti-Aging Symposium [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- A Major Breakthrough in Skin Care and Nutrition [Last Updated On: July 17th, 2011] [Originally Added On: July 17th, 2011]
- Elaine Fuchs Part 1: Introduction to Stem Cells [Last Updated On: July 20th, 2011] [Originally Added On: July 20th, 2011]
- World's 1st Nutricosmetic with Stem Cell Nutrients [Last Updated On: July 21st, 2011] [Originally Added On: July 21st, 2011]
- Stem cells acquired from human skin [Last Updated On: August 9th, 2011] [Originally Added On: August 9th, 2011]
- Stem cells acquired from human skin [Last Updated On: August 17th, 2011] [Originally Added On: August 17th, 2011]
- DermaStem Renewal Serum - Stem Cells for Your Skin from STEMTech - New Paradigm in Beauty! [Last Updated On: August 19th, 2011] [Originally Added On: August 19th, 2011]
- DermaStem Renewal Serum - Stem Cells for Your Skin from STEMTech - New Paradigm in Beauty! [Last Updated On: August 30th, 2011] [Originally Added On: August 30th, 2011]
- ReLuma-stemcells- skin rejuvenation [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Dr Nathan Newman- Formulator of Stem Cell Skin Care Line LUMINESCE [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Genetic Skin Disease (EB): Spotlight on Stem Cell Research - Patient Advocate [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Genetic Skin Disease (EB): Spotlight on Stem Cell Research - Patient Advocate [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Stem Cell Skin Care- What is the role of stem cells in Luminesce Featuring Dr Nathan Newman [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- Luminesce Stem Cell Skin Care - Leaders in Jeunesse [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- Stem Cell Skin Care- What is the role of stem cells in Luminesce Featuring Dr Nathan Newman [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- Isolation and Culture of Adult Epithelial Stem Cells from Human Skin [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- Genetic Skin Disease (EB): Spotlight on Stem Cell Research - Welcome [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- Stem Cells Made From Human Skin [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- Jeunesse Global Business Opportunity with Stem Cell Skin Care Developed by Dr Nathan Newman [Last Updated On: September 10th, 2011] [Originally Added On: September 10th, 2011]
- Stem Cell Therapy Skin Repair and Anti-Wrinkle Cream [Last Updated On: September 10th, 2011] [Originally Added On: September 10th, 2011]
- Stem Cells Made From Human Skin [Last Updated On: September 10th, 2011] [Originally Added On: September 10th, 2011]
- Genetic Skin Disease (EB): Optimizing Embryonic Stem Cell Differentiation Protocols [Last Updated On: September 10th, 2011] [Originally Added On: September 10th, 2011]
- Genetic Skin Disease (EB): Spotlight on Stem Cell Research - Introduction [Last Updated On: September 11th, 2011] [Originally Added On: September 11th, 2011]
- Isolation and Culture of Adult Epithelial Stem Cells from Human Skin [Last Updated On: September 11th, 2011] [Originally Added On: September 11th, 2011]
- Stem Cell Therapy - BioLogic Anti-Aging Skin Cream [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- Best natural skin care serum using stem cell technology [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- Jeunesse Global Business Opportunity with Stem Cell Skin Care Developed by Dr Nathan Newman [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- Genetic Skin Disease (EB): Optimizing Embryonic Stem Cell Differentiation Protocols [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- Research on skin cancer: ERC funds studies on stem cells [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Skin engineering [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Stem Cell Banking: The Perspective of an iPS Donor Family [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Jeunesse Global Opportunity- Stem Cell Skin Care [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Dr Nathan Newman Repairs Laugh Lines With Stem Cell Face Lift [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Dr Nathan Newman MD Stem Cell Face lift On Extra TV.flv [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Dr Nathan Newman Stem Cell Face Lift on Entertainment Tonight [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Dr Nathan Newman MD Stem Cell Face lift On Good Morning LA.flv [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Ellis Martin Report with International Stem Cell Corp [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- Dr Nathan Newman MD Stem Cell Face lift on Channel 7 KABC.flv [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- Stem Cell Face Treatment - What People Are Saying | Beverly Hills | Los Angeles [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- How To Use Your Stem Cells For Facial Skin Rejuvenation [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- StemCellTV - From National Geographic - The Skin Gun - Healing Burns with Stem Cells [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- AMAZING - Stem Cell Skin Cream And Liquid Face Lift Revealed [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- Care for Your Skin with Lifeline Skin Care [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- For Damaged Skin - Rejuvenate Your Own Stem Cells [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting [Last Updated On: September 28th, 2011] [Originally Added On: September 28th, 2011]
- Dr.Thomas Barnes' PRP Hair Growth and Skin Rejuvenation [Last Updated On: September 28th, 2011] [Originally Added On: September 28th, 2011]
- Stem Cell Face Lift - English (Part 5) [Last Updated On: September 28th, 2011] [Originally Added On: September 28th, 2011]
- Dr Amiya Prasad discusses ACell for Hair Regrowth and Skin Rejuvenation with EYES IN Magazine [Last Updated On: September 30th, 2011] [Originally Added On: September 30th, 2011]
- Brussels scientist close to discovering skin cancer origins [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Cell Reprogramming Transformed [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Cell Reprogramming Transformed [Last Updated On: October 7th, 2011] [Originally Added On: October 7th, 2011]
- Elaine Fuchs Part 1: Introduction to Stem Cells English Subtitle [Last Updated On: October 10th, 2011] [Originally Added On: October 10th, 2011]
- Elaine Fuchs Part 1: Introduction to Stem Cells English Subtitle [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Elaine Fuchs discusses research on skin and adult stem cells - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Signals Stem Cell Skin Care Anti Aging Skin Care - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]