AstraZenecon Calquence first-line treatment CLL III clinical success

British pharmaceutical giant AstraZeneca recently released the first data from a Phase III ELEVATE-TN study evaluating the first-line treatment of chronic lymphocytic leukemia (CLL) at the targeted cancer drug Calquence. The study reached its main end point in the medium-term analysis, and this is the second key Phase III study of Calquence's treatment of CLL, following the ASCEND study published in May this year.ELEVATE-TN (ACE-CL-007) is a randomized, multi-center, open-label Phase III study conducted in patients with previously un treated (primary treatment) CLL to assess the efficacy and safety of Calquence monotherapy, Calquence-obinutuzumab combination therapy and benzodiazepine nitrogen mustard-outuzumab combination therapy. In the study, 535 patients were randomly divided into three groups (1:1:1): the first group received a combination therapy of benzoic acid nitrogen mustard and obinutuzumab, the second group received Calquence (100mg 2 times a day until the progression of the disease) and the third group received Calquence monotherapy (100mg 2 times a day until the progression of the disease). The main endpoint was to compare the progress-free lifetime (PFS) assessed by the Independent Review Commission (IRC) in the co-treatment group calquence-obinutuzumab and the benzodiazepine-obinutuzumab joint treatment group. The key secondary endpoint was the PFS assessed by the IRC in the Calquence single-drug group in a joint treatment group with benzodiazepine nitrogen mustard and obinutuzumab. Other secondary endpoints include objective mitigation rate (ORR), next treatment time, total lifetime (OS).The results showed that the study reached the main endpoint: Calquence-obinutuzumab combined therapy significantly reduced the risk of disease progress or death by 90% (HR-0.10) compared to chemotherapy-based benzodiazepine-obinutuzumab combination therapy. 95% CI: 0.06-0.17, p<0.0001), PFS achieve statistically significant and clinically significant improvements (medium PFS: not up to vs 22.6 months). In addition, the study reached a critical secondary endpoint, with Calquence monotherapy significantly reducing the risk of disease progression or death by 80 per cent (HR-0.20) compared to chemotherapy-based benzodiazepines and obinutuzumab combination therapies. 5% CI: 0.13-0.30, p<0.0001), PFS achieve statistically significant and clinically significant improvements (medium PFS: not up to vs 22.6 months). In this study, Calquence's safety and tolerance were consistent with the drug's identified profile.The full data for the study will be presented at the 2019 annual meeting of the American Society of Hematology (ASH) in Orlando from December 7-10.In June, AstraZeneca released its first key Phase III study of ASCEND's interim analysis. The study, conducted in patients with recurring or refractic CLL, compared the efficacy and safety of Calquence with the treatment options chosen by the doctor, IdR (lytoxidan-idelalisib) or BR (lytoxi monoanti-benzomostin). The results showed that by the time of the interim analysis, the study had reached its primary endpoint: Calquence significantly extended the disease-free progressive survival time of patients with relapsed or resuscable CLL compared to the treatment options chosen by doctors. The data for the median follow-up period of 16.1 months showed that patients treated with Calquence had a statistically and clinically significant improvement, a 69% reduction in disease progression or risk of death compared to the IdR or BR programme (HR=0.31,95%CI:0.20-0.49; p<0.0001). At the time of data analysis, the median PFS in the Calquence treatment group had not yet been reached, and the median PFS in the control group was 16.5 months. At the 12th month, 88 percent of patients in the Calquence treatment group had no progression, compared with 68 percent in the control group. In this study, Calquence's safety and tolerance were consistent with the identified characteristics of the drug.ELEVATE-TN studies and ASCEND studies confirm the superiority of Calquence as a monotherapy and as a combination therapy over CLL standard nursing therapy. Based on the data from these two Phase III studies, AstraZeneta has filed a regulatory application with the FDA for Calquence for first-line treatment and relapse/difficulty treating CLL. In June, the FDA granted Calquence a breakthrough drug qualification (BTD) for single-drug treatment CLL, the 10th BTD AstraZeneta has received from the FDA since 2014.Calquence: The BTK inhibitor Calquence, which is expected to have annual sales of more than $5 billion, was approved by the FDA in October 2017 for adult patients with recurring or refractive myoblastoma (MCL) who have received at least one treatment in the past. Currently, the drug is being developed to treat CLL and other malignant tumors of the blood system.Calquence's active pharmaceutical ingredient is acalabrutinib, a highly selective, powerful, co-priced Bruton tyrosine kinase (BTK) inhibitor that inhibits BTK through permanent binding. BTK is the key regulatory factor of B cell subject (BCR) signaling path, widely expressed in different types of blood system malignancies, involved in the proliferation, transportation, adhesion and adhesion of B cells, and is therefore an important target for the treatment of malignant tumors in the blood system. In preclinical studies, acalabrutinib showed minimal off-target effects.Currently, Calquence is being developed for a variety of B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom globulinemia (WM), fiery lymphoma (FL), multiple myeloma, and other hematological malignancies. AstraZeneta has high commercial expectations for Calquence, with sales of the drug expected to peak at $5 billion!Calquence's mechanism of effect is the same as that of Ibruvica (ibrutinib, ibrutinib), the world's first approved BTK inhibitor. Since its first approval in November 2013, Imbruvica has been approved for up to 10 therapeutic adaptations in six disease areas, and global sales have skyrocketed. Just recently, Evaluate Pharma, a pharmaceutical market research organization, released a report predicting that Imbruvica's global sales will reach $9.5 billion by 2024, making it the world's fifth-best-selling drug. (Bio Valley)