On June 12, 2020 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage drug development company focused on the registration and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that Long-Term Safety and Dose Intensity data for momelotinib are being presented today in two posters at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (Press release, Sierra Oncology, JUN 12, 2020, View Source [SID1234561029]).

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More than 820 patients with myelofibrosis have received momelotinib during its development, including a number of patients who remain on treatment since the start of the original Phase 2 studies initiated a decade ago. One of these patients will reach a major milestone this week, having received momelotinib therapy for 10 years, highlighting the relevance of the long-term dosing and safety data for momelotinib being presented this week at EHA (Free EHA Whitepaper). The data presented at EHA (Free EHA Whitepaper) draw from more than 550 patients across the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods. More than 90 SIMPLIFY-1 and SIMPLIFY-2 patients continued to receive momelotinib for 3.5 years or longer.

"Consistent with prior data, and reflecting momelotinib’s differentiated pharmacological profile, our new long-term safety analyses continue to show a rapid and sustained increase in hemoglobin levels during momelotinib therapy, in contrast to the significant decrease in hemoglobin for patients receiving ruxolitinib. Patients treated with momelotinib also experienced significantly higher mean platelet counts compared to those receiving ruxolitinib. Importantly, patients who switched from ruxolitinib to momelotinib also achieved a sustained improvement in both hemoglobin and platelets," said Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. "In addition to an absence of significant rates of high-grade hematological toxicities, long-term tolerability was favorable with no new safety signals or evidence of cumulative toxicity. Notably, this was achieved with most patients receiving full-dose momelotinib."

"Momelotinib’s safety profile and durable anemia benefits facilitated sustained dose intensity across the continuum of JAK inhibitor naïve and previously JAK inhibitor treated myelofibrosis patients. While the starting doses for ruxolitinib were often attenuated due to low platelets, further reductions in dose intensity were also commonly required for ruxolitinib. In contrast, momelotinib was initiated at full dose for all subjects enrolled to the SIMPLIFY studies and high dose intensity was maintained in the majority over extended durations," said Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, Canada. "The ability to safely dose momelotinib sustainably at high dose intensity likely facilitates its ability to durably control the cardinal features of myelofibrosis, namely anemia, constitutional symptoms, and splenomegaly. Furthermore, patients who switch from ruxolitinib to momelotinib saw an immediate and sustained improvement in dose intensity, suggesting a link to the corresponding improvements in hemoglobin and platelets noted by Prof. Harrison. These data suggest that momelotinib may be an optimal therapy in myelofibrosis patients, in particular those experiencing hematological toxicity and disease-related myelosuppression, which are significant unmet needs in this disease."

The SIMPLIFY-1 trial was conducted in JAKi-naïve myelofibrosis patients (n=432) randomized 1:1 to momelotinib or ruxolitinib for 24 weeks. The SIMPLIFY-2 trial was conducted in prior ruxolitinib-treated myelofibrosis patients with hematological toxicity (n=156) randomized 2:1 to momelotinib or best available therapy (consisting of ruxolitinib in 88% of patients) for 24 weeks. All patients were then subsequently allowed to receive momelotinib for an extended treatment period including those who did not receive momelotinib initially, as they were eligible to cross-over to momelotinib at the end of the 24-week randomized treatment period in both studies.

About the Posters:
Please visit www.sierraoncology.com to view Prof. Harrison and Dr. Gupta present the momelotinib Long-Term Safety and Dose Intensity posters. Both e-posters are available through the on-demand EHA (Free EHA Whitepaper) Virtual Congress platform at View Source

Title: Long term Safety of Momelotinib in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1113

Title: Momelotinib Dose-Intensity is Maintained in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, ON, Canada
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1103

On June 12, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated data on one of its investigational CD20xCD3 T-cell engaging bispecific antibodies, glofitamab (formerly known as CD20-TCB), in people with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Hoffmann-La Roche, JUN 12, 2020, View Source [SID1234561027]). Updated results from the phase I dose-escalation NP30179 study [NCT03075696] of glofitamab, administered via intravenous infusion for a fixed-duration of up to 12 21-day cycles, showed durable complete responses (CRs) in heavily pre-treated patients who had received a median of three prior lines of therapy. These data feature in an oral presentation (abstract #S241) at the European Hematology Association (EHA) (Free EHA Whitepaper) 25th Annual Congress Virtual Edition, taking place from 11-14 June 2020.

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"Non-Hodgkin lymphomas such as diffuse large B-cell lymphoma may present considerable treatment challenges, especially cases involving multiple relapses," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We’re encouraged by these early results which support the potential of glofitamab for patients who have failed multiple prior lines of therapy and need new treatment options urgently."

Updated efficacy data from the ≥0.6mg and ≥10mg cohorts showed high response rates across NHL subtypes.

In the ≥0.6mg cohorts, the investigator-assessed CR rate was 30.9% (38/123) for patients with aggressive NHL and the investigator-assessed overall response rate (ORR) was 45.5% (56/123). For patients with indolent NHL, the investigator-assessed CR rate was 52.2% (12/23) and the investigator-assessed ORR was 65.2% (15/23).
In the ≥10mg cohorts, the investigator-assessed CR rate was 34.1% (29/85) for patients with aggressive NHL and the investigator-assessed ORR was 49.4% (42/85). For patients with indolent NHL, the investigator-assessed CR rate was 50.0% (9/18) and the investigator-assessed ORR was 66.7% (12/18).
CRs also appeared durable. Of the patients achieving a CR in the ≥0.6mg cohorts, 72.7% (24/33) with aggressive NHL and 81.8% (9/11) with indolent NHL maintained their CR by the data cut-off date (17 April 2020). Median duration of CR was not reached in either group after a median follow-up of 10.2 months.
The safety profile of glofitamab was consistent with its mechanism of action. Common adverse events (AEs) occurring in over 15% of participants in the ≥0.6mg cohorts (n=156) were cytokine release syndrome (CRS; n=88, 56.4%), neutropenia (n=48, 30.8%), pyrexia (n=47, 30.1%), anaemia (n=35, 22.4%) and thrombocytopenia (n=26, 16.7%). The majority of CRS events were low grade (Grade 1-2), were associated with the first cycle, and were manageable.

A robust clinical development programme for glofitamab is ongoing, investigating the molecule alone and in combination with other Roche and non-Roche molecules. Combination regimens include studies with Polivy (polatuzumab vedotin), Tecentriq (atezolizumab), MabThera/Rituxan (rituximab) and Gazyva/Gazyvaro (obinutuzumab) in NHL and other blood cancers, across a variety of settings and tumour types, including earlier treatment lines, to identify where glofitamab may be able to provide benefit over current treatment options.

About glofitamab
Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Glofitamab is based on a novel structural format which we call ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. A robust clinical development programme for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, and other blood cancers.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed dose of Gazyva/Gazyvaro, in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 12, 2020 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) reported that three posters relating to the MANIFEST clinical trial of CPI-0610 in myelofibrosis (MF) were published online in association with the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting (Press release, Constellation Pharmaceuticals, JUN 12, 2020, View Source [SID1234561026]). The data in these posters are based on a data cutoff of April 17, 2020, and reflect an analysis of clinical activity in 51 first-line (1L) and 73 second-line (2L) patients.

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"I’m encouraged that the initial signals of activity with CPI-0610, such as spleen and symptom responses, that were presented last December at ASH (Free ASH Whitepaper) continue to be observed in a larger dataset presented in these EHA (Free EHA Whitepaper) posters," said Claire Harrison, D.M. (Oxon.), Professor of Haematology and a MANIFEST investigator. "In addition, we continue to see signals of disease modification, such as increases in hemoglobin, conversions of transfusion-dependent patients to transfusion independence, and bone marrow fibrosis improvements. If corroborated in further testing, these data suggest that CPI-0610 could potentially change the treatment paradigm in MF."

"We are excited about the emerging profile of CPI-0610," said Jigar Raythatha, Chief Executive Officer of Constellation Pharmaceuticals. "Our goal is to drive CPI-0610 to registration and to transform the standard of care in myelofibrosis and potentially other hematologic diseases."

Data Highlights

Arm 3 (1L) – CPI-0610 + ruxolitinib in JAK-inhibitor-naïve patients

37 of 51 evaluable patients (73%) achieved a 35% reduction in spleen volume (SVR35) at 12 weeks and had a median spleen volume reduction of 51%
19 of 30 evaluable patients (63%) achieved SVR35 at 24 weeks (the primary endpoint for Arm 3) and had a median spleen volume reduction of 53%
17 of 29 evaluable patients (59%) achieved a 50% improvement in Total Symptom Score (TSS50) at 24 weeks and had a median TSS improvement of 64%
No evidence of correlation between SVR35 response and baseline risk status, platelet count, or spleen volume
Arm 1 (2L) – CPI-0610 monotherapy in JAK-inhibitor-experienced or -ineligible patients

3 of 14 (21%) evaluable transfusion-dependent (TD) patients converted to transfusion independence (TI), the primary endpoint for cohort 1A
5 of 21 (24%) evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 1B) and 9 of 19 (47%) evaluable non-TD patients achieved TSS50 at 24 weeks
11 of 19 (58%) non-TD patients on treatment for at least 12 weeks without any transfusions achieved a ≥1.5 g/dL mean increase in hemoglobin
Arm 2 (2L) – CPI-0610 + ruxolitinib in ruxolitinib-experienced patients

11 of 32 (34%) evaluable TD patients converted to TI, the primary endpoint for cohort 2A
4 of 18 (22%) evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 2B) and 7 of 19 (37%) evaluable non-TD patients achieved TSS50 at 24 weeks
Safety

CPI-0610 in MANIFEST, both as monotherapy and in combination with ruxolitinib and in both JAK-inhibitor-naïve and JAK-inhibitor-experienced and -ineligible patients, was generally well tolerated.

Among the most common treatment-emergent adverse events (TEAEs) for CPI-0610 monotherapy in 43 safety-evaluable patients in Arm 1, those that were Grade 3 were thrombocytopenia (14.0%), anemia (9.3%), diarrhea (4.7%), and respiratory tract infection (2.3%). Six patients discontinued treatment because of TEAEs. There were no Grade 4 or Grade 5 TEAEs.

Among the most common TEAEs in 70 safety-evaluable patients in Arm 2, those that were Grade 3 were thrombocytopenia (22.9%), anemia (7.1%), fatigue (5.7%), diarrhea (4.3%), respiratory tract infections (4.3%), nausea (2.9%), and abdominal pain (1.4%). Grade 4 TEAEs included thrombocytopenia (1.4%) and anemia (1.4%). Seven patients discontinued treatment due to TEAEs, including four Grade 5 TEAEs, which were acute kidney injury, traumatic subdural hematoma, brain stem hemorrhage (no concomitant thrombocytopenia), and disease progression.

Among the most common TEAEs in 64 safety-evaluable patients in Arm 3, those that were Grade 3 were anemia (15.6%), respiratory tract infections (3.1%), and thrombocytopenia (1.6%). Grade 4 TEAEs included thrombocytopenia (3.1%), anemia (1.6%), and respiratory tract infection (1.6%). Four patients discontinued treatment due to TEAEs, including two Grade 5 TEAEs, each due to multi-organ failure due to sepsis.

For further details, please see the EHA (Free EHA Whitepaper) poster presentations here.

EHA Poster Presentations

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, in Combination with Ruxolitinib, in JAK Inhibitor Treatment Naive Myelofibrosis Patients: Update of MANIFEST Phase 2 Study (Presentation Code: EP1084)

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as Monotherapy in Advanced Myelofibrosis Patients Refractory / Intolerant to JAK Inhibitor: Update from Phase 2 MANIFEST Study (Presentation Code: EP1091)

TITLE: CPI-0610, Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as "Add-on" to Ruxolitinib (Rux), in Advanced Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST Phase 2 Study (Presentation Code: EP1083)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

Investor Event

Constellation will host a virtual analyst/investor event and conference call on June 12 at 8:00 AM EDT to discuss the data from these three posters relating to the MANIFEST clinical trial for CPI-0610 being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) meeting. The agenda of the event will include:

An overview of myelofibrosis (MF) and the potential impact of Constellation’s BET inhibitor CPI-0610 in treating MF
A review of the data from the MANIFEST clinical trial presented in the EHA (Free EHA Whitepaper) posters
A live question-and-answer session
The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at View Source To participate in the live question-and-answer session, please dial (877) 473-2077 (domestic) or (661) 378-9662 (international) and refer to conference ID 6275774.

EZH2 Program Prioritization

Constellation reported that it plans to prioritize further clinical development of its next-generation EZH2 inhibitor CPI-0209. The decision is based on a recent data cut and review of ProSTAR, the ongoing Phase 1b/2 clinical study evaluating CPI-1205, a small-molecule inhibitor of EZH2, combined with enzalutamide or abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). The data did not demonstrate the definitive signal of activity necessary to advance the program into pivotal studies in mCRPC. A full data set from ProSTAR will be presented at a future medical meeting.

"We thank the patients and investigators who participated in ProSTAR," said Jigar Raythatha. "While we are disappointed with the outcome of this study, we remain committed to EZH2 as an important cancer target and will apply the learnings from ProSTAR to our second-generation EZH2 inhibitor, CPI-0209. We believe the deeper and more durable target engagement as well as the improved metabolic properties that CPI-0209 demonstrated in preclinical studies give it the potential to be a best-in-class EZH2 inhibitor for use in a broad range of cancer types. CPI-0209 is progressing through the dose escalation portion of a phase 1/2 clinical trial, and we expect to determine a recommended Phase 2 dose later in the year."

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

About ProSTAR

ProSTAR is an open-label Phase 1b/2 clinical trial of CPI-1205, a potent and highly selective small-molecule EZH2 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) in the second-line setting. The ProSTAR study is evaluating CPI-1205 in combination with either enzalutamide or abiraterone/prednisone ("abiraterone"), which are androgen receptor signaling (ARS) inhibitors, in mCRPC patients who experienced disease progression while receiving the other ARS inhibitor.

On June 12, 2020 AstraZeneca reported that Detailed results from both the Phase II ACE-CL-001 trial and the pivotal Phase III ASCEND trial showed the long-term efficacy and tolerability of Calquence (acalabrutinib) in chronic lymphocytic leukaemia (CLL), one of the most common types of adult leukaemia.1,2,3 (Press release, AstraZeneca, JUN 12, 2020, View Source [SID1234561024])

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The results will be presented during the Virtual Edition of the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, 11 to 14 June 2020.

In the single-arm ACE-CL-001 trial, 86% of CLL patients treated with Calquence as a 1st-line monotherapy remained on treatment at a median follow up of more than four years. The trial showed an overall response rate of 97% (7% complete response; 90% partial response) and a 100% overall response rate in subgroups of patients with high-risk disease characteristics, including genomic aberrations (17p deletion and TP53 mutation), immunoglobulin mutation status (unmutated IGHV), and complex karyotype. Safety findings showed no new long-term issues.1,4

In the final analysis of ASCEND, an estimated 82% of patients with relapsed or refractory CLL treated with Calquence remained alive and free from disease progression at 18 months compared with 48% of patients on rituximab combined with idelalisib or bendamustine.2 The trial previously met the primary endpoint of Independent Review Committee-assessed progression-free survival at the interim analysis.5

Richard R. Furman, Director of the CLL Research Center, Weill Cornell Medicine said: "These data demonstrate no new safety concerns for acalabrutinib, confirming its ability to safely provide meaningful, long-term clinical benefit for patients with treatment-naive and relapsed or refractory disease. The safety profile of acalabrutinib makes treatment to progression an important and plausible option for patients."

José Baselga, Executive Vice President, Oncology R&D said: "These long-term data reaffirm that Calquence delivers a durable response with a favourable safety profile for chronic lymphocytic leukaemia patients. Patients with chronic lymphocytic leukaemia are typically 70 years or older with comorbidities and often require treatment over a long time, making the sustained safety and efficacy profile highly relevant to their quality of life."

Results from the Phase II ACE-CL-001 trial informed the development of the pivotal Phase III ELEVATE TN trial, which, along with findings from the Phase III ASCEND trial, formed the basis for the US approval of Calquence for the treatment of patients with CLL or small lymphocytic lymphoma (SLL).

Calquence in previously untreated CLL: 4.4-year follow-up from Phase II trial (abstract #S163)

The Phase II ACE-CL-001 trial investigated safety and efficacy of Calquence (100mg twice-daily [n=62] or 200mg once-daily [n=37]) in previously untreated patients with CLL.1 On 1 May 2015, patients receiving the 200mg dosing regimen were switched to the 100mg regimen.1

Key data from the Calquence Phase II ACE-CL-001 trial1

Calquence Phase II ACE-CL-001 trial table
CI, confidence interval; CR, complete response; DoR, duration of response; EFS, event free survival; TTR, time to response; NR, not reached; ORR, overall response rate; PR, partial response

Response rates were 100% in each subgroup of patients with high-risk disease characteristics (unmutated IGHV [n=57], 17p deletion [n=9], TP53 mutation [n=9], and complex karyotype [n=12]), and reduction in lymph node disease was noted in all patients tested (n=97).1

At the time of data cut-off, 85 (86%) patients receiving Calquence remained on treatment. Six patients discontinued treatment due to adverse events (AEs) and three patients discontinued for progressive disease (PD). No patient discontinued Calquence due to bleeding events, hypertension, or atrial fibrillation. Incidence of AEs generally diminished with time on the trial. The most common AEs (≥40%) of any grade in the trial were diarrhoea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and Grade ≥3 events of clinical interest included infection (84% and 15%, respectively), bleeding events (66%, 3%), hypertension (22%, 11%), leukopenia (9%, 9%), and thrombocytopenia (3%, 1%). Atrial fibrillation (all grades) occurred in 5% of patients with Grade ≥3 occurring in 2%. Second primary malignancies (SPM) excluding non-melanoma skin (all grades) occurred in 11% of patients.1 Serious adverse events (SAEs) were reported in 38% of patients. SAEs occurring in more than two patients included pneumonia (n=4) and sepsis (n=3).1

Final results of Calquence Phase III ASCEND trial in relapsed or refractory CLL (abstract #S159)

ASCEND was a global, randomised, multicentre, open-label, Phase III trial that investigated the efficacy and safety of Calquence (100mg twice-daily) versus investigator’s choice of rituximab combined with idelalisib (IdR) or bendamustine (BR) in patients with relapsed or refractory CLL.2

Key data from the final analysis of the Calquence Phase III ASCEND trial2

Calquence Phase III ASCEND trial table
BR, rituximab in combination with bendamustine; CI, confidence interval, DoR, duration of response; HR, hazard ratio; IdR, rituximab in combination with idelalisib; INV, investigator; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival

Sixteen per cent of patients on Calquence, 56% of patients on IdR, and 17% of patients on BR discontinued treatment because of AEs. Common AEs occurring in greater than 15% of patients of any grade in the Calquence arm of the trial included headache (22%), neutropenia (21%), diarrhoea (20%), upper respiratory tract infection (20%), cough (16%), and anaemia (16%). Events of clinical interest for Calquence versus controls included atrial fibrillation (all grade, 6% and 3%, respectively), major haemorrhage (all grade, 3% in both arms), infections (Grade ≥3, 20% and 25%, respectively), and SPM excluding non-melanoma skin cancer (all grade, 5% and 2%, respectively). SAEs (any grade) occurred in 33% of patients receiving Calquence, 56% of IdR patients, and 26% of BR patients.2

Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is one of the most common types of leukaemia in adults, with an estimated 105,000 new cases globally in 2016 and 21,040 new cases in the US in 2020, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.3,6,7,8 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.3 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets.3 This could result in anaemia, infection, and bleeding.3 B-cell receptor signalling through Bruton’s tyrosine kinase is one of the essential growth pathways for CLL.

Calquence

Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.4,9 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.4

Calquence is approved for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) in nine countries and for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in 14 countries. The US MCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 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, Waldenström macroglobulinaemia, follicular lymphoma, and other haematologic malignancies.

AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s 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 AstraZeneca’s 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.

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 six new medicines 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 AstraZeneca’s 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.

On June 11, 2020 Avalon GloboCare Corp. (NASDAQ: AVCO), a clinical-stage global developer of cell-based technologies and therapeutics, reported that it has entered into a three-way material transfer agreement (MTA) with Weill Cornell Medicine in New York City and the Company’s strategic partner, Arbele Limited (Press release, Avalon, JUN 11, 2020, View Source [SID1234609547]).

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With this agreement, Avalon GloboCare Corp. and Arbele Limited intend to collaborate with Weill Cornell Medicine and co-develop the standardized laboratory steps necessary to generate clinical-grade CAR-T and CAR-NK cells for use in future human clinical trials with Avalon’s first FLASH-CAR(TM) platform candidate, AVA-011. This step, called process development, will provide the bridge between Avalon’s benchtop research and the bio-manufacturing processes to potentially deliver the clinical-grade cellular immunotherapy product to patients.

"We are excited about this agreement to translate our cellular therapy candidates into standardized, clinical-grade cell products that could be used in future clinical trials. This step reflects our dedication to establishing an infrastructure to develop our cellular immunotherapy candidates and to maintain the highest possible standards for generating clinical-grade cells for human cancer trials," stated David Jin, M.D., Ph.D., President and Chief Executive Officer of Avalon GloboCare.

AVA-011 is a next generation cellular immunotherapy candidate using Avalon’s FLASH-CAR(TM) that targets both CD19 and CD22 tumor antigens on cancer cells. Avalon has already successfully completed pre-clinical research on AVA-011, including tumor cytotoxicity studies. (See May 8, 2020 press release, ‘Avalon GloboCare Advances Next Generation Cellular Immunotherapy with FLASH-CAR(TM) Technology for Blood Cancers’)

Avalon’s next generation immune cell therapy using FLASH-CAR(TM) technology is being co-developed with the Company’s strategic partner Arbele Limited. The adaptable FLASH-CAR(TM) platform may be used to create personalized cancer cell therapy from a patient’s own cells, as well as off-the-shelf cell therapy from a universal donor, expanding the reach of cancer patients that could be treated.