On September 4, 2023 AstraZeneca reported that Calquence (acalabrutinib), a next generation, selective Bruton’s tyrosine kinase (BTK) inhibitor, has been approved in China for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy (Press release, AstraZeneca, SEP 4, 2023, View Source [SID1234634856]).

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The approval by the National Medical Products Administration (NMPA) was based on positive results from two clinical trials, including the ASCEND Phase III trial of Calquence versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) for patients with relapsed or refractory (R/R) CLL and an open-label, single-arm Phase I/II trial in China for patients with R/R CLL.1,2

CLL is the most prevalent type of adult leukaemia across the globe and represents approximately 6.4% of B-cell non-Hodgkin lymphoma patients in China.3

Professor Li Jianyong, Director of Haematology, People’s Hospital of Jiangsu Province, and Leader of China CLL Working Group, said: "Many people living with chronic lymphocytic leukaemia experience relapse and need additional treatment options to help manage their disease. I’m delighted that with this approval patients now have access to an established treatment that has already demonstrated effectiveness in many patients across the globe."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Today’s approval is another step towards our goal of making Calquence available to as many patients as possible and offering physicians a treatment option with a well-established efficacy and tolerability profile. Patients with chronic lymphocytic leukaemia are often older and dealing with significant comorbidities, and tolerability is a critical factor in their treatment."

In the ASCEND Phase III trial, 88% of patients with R/R CLL treated with Calquence were alive and free from disease progression after 12 months compared with 68% of patients treated with IdR/BR.1 Longer-term follow-up data showed 62% of patients treated with Calquence were alive and had not progressed at 42 months versus 19% of patients treated with IdR/BR.

Additionally, results from a Phase I/II trial in Chinese adults with R/R CLL showed Calquence achieved an overall response rate (ORR) of 83.3%. At a median follow-up of 20.2 months, median progression-free survival (PFS) was not reached and the 12-month and 18-month PFS rates were 90.7% and 78.8%, respectively. The safety and tolerability of Calquence in these trials were consistent with that observed in previous clinical trials.1,2

Calquence is approved for the treatment of CLL and SLL in the US and Japan and is approved for the treatment of CLL in the EU and in several other countries worldwide in the treatment-naïve and R/R settings. Calquence is also approved in the US, China and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

Notes

CLL
CLL is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019.4 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.5 In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow and in blood and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anaemia, infection and bleeding.6 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

ASCEND
ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in patients with relapsed or refractory CLL.1

In the trial, 310 patients were randomised (1:1) into two treatment arms.1 Patients in the first arm received Calquence monotherapy (100mg twice-daily until disease progression or unacceptable toxicity).1 Patients in the second arm received physician’s choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3-kinase inhibitor, or rituximab in combination with bendamustine, a chemotherapy.1

The primary endpoint at the interim analysis was PFS assessed by an independent review committee (IRC), and key secondary endpoints included investigator-assessed PFS, IRC and investigator-assessed ORR and duration of response, as well as overall survival (OS), patient-reported outcomes and time to next treatment.1

ASCEND is the first randomised Phase III trial to directly compare a BTK inhibitor as monotherapy to these combinations in relapsed or refractory CLL.1

Phase I/II trial in Chinese patients
The Phase I/II trial is an open-label, multicentre clinical trial evaluating pharmacokinetics, tolerability, safety and clinical efficacy of Calquence in adult Chinese patients with CLL who have received at least one prior therapy and other B-cell malignancies.2 In Phase I, patients with relapsed or refractory B-cell malignancies received a single dose of Calquence 100mg orally followed by a two-day washout period and subsequent treatment with Calquence 100mg orally twice daily in 28-day cycles, until progressive disease (PD) or treatment discontinuation (TD) for any other reason.2 In Phase II, patients with relapsed or refractory CLL (n=60) received Calquence 100mg orally twice daily until PD or TD for any other reason.2 The primary efficacy endpoint was ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 classification assessed by Blinded Independent Central Review (BICR).2 Secondary endpoints were investigator-assessed ORR, BICR- and investigator-assessed time to response, duration of response and PFS, OS, safety including adverse events and Calquence plasma concentration.2

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.7 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence has been used to treat 50,000 patients worldwide and is approved for the treatment of CLL and SLL in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL.

As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, marginal zone lymphoma and other haematologic malignancies.

On September 4, 2023 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported that its Phase 1 MAST (metastatic advanced solid tumours) trial evaluating the safety of novel cancer-killing virus CF33-hNIS (VAXINIA) has cleared cohort 1 of the intratumoral (IT) arm of the combination study where VAXINIA is administered in combination with Pembrolizumab (Press release, Imugene, SEP 4, 2023, View Source [SID1234634855]).

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As a result, Imugene is now recruiting for cohort 2 of each of the arms (IT and intravenous/IV) in the combination study, in addition to cohort 4 of each of the arms of the monotherapy dose escalation.Imugene MD & CEO Leslie Chong said: "We’ve now seen a very significant number of patients dosed with VAXINIA as part of the MAST study, with those patients suffering as a result of a variety of tumour types. It’s exciting that we’re getting so close to finding out the impact that this treatment is having for these patients in need."

The multicenter Phase 1 MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. The City of Hope-developed oncolytic virus has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models. Overall, the study aims to recruit up to 100 patients across approximately 10 trial sites in the United States and Australia.

The clinical trial is titled "A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33- hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination with Pembrolizumab in Adult Patients with Metastatic or Advanced Solid Tumours (MAST)." The trial commenced in May 2022 and is anticipated to run for approximately 24 months while being funded from existing budgets and resources.

On September 1, 2023 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the following statement about the closure of COBRA, a minimum residual disease (MRD) study (Press release, Guardant Health, SEP 1, 2023, View Source [SID1234634848]).

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The COBRA study was designed to evaluate the effectiveness of using MRD testing to improve clinical outcomes in patients with stage II colon cancer after curative-intent surgery with a planned final readout in 2026.

"Our MRD test has great potential to help patients and their doctors stay ahead of cancer, and we remain confident about its promise to vastly improve patient care and its continued prospects for broad access and reimbursement," said Craig Eagle, MD, Guardant Health chief medical officer.

"We agree with the decision, based on the recent planned interim analysis, to close the COBRA study to new enrollees," said Dr. Eagle. "The field has progressed rapidly since the study was designed over four years ago, and since the study was initiated we have made tremendous progress with multiple upgrades of our MRD test. Additionally, we have many ongoing studies that will demonstrate the effectiveness of our current MRD tests in colorectal cancer and other settings."

On September 1, 2023 Medivir AB (NASDAQ Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that it will host a key opinion leader webcast on the current and future HCC (primary liver cancer) treatment landscape, including how treatment challenges and needs in HCC differs from most other cancers (Press release, Medivir, SEP 1, 2023, View Source [SID1234634847]). The webcast will take place on September 8, 2023 at 13:00 CET/07:00 EST.

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The webcast will feature presentations by Dr. Jeff Evans, Beatson West of Scotland Cancer Center, Glasgow, UK, who will discuss the current treatment landscape and unmet medical need in treating patients with HCC. He will be joined by Dr. Maria Reig, Liver Cancer Unit, Hospital Clínic BCLC group, Villarroel, Barcelona, Spain, who will discuss how HCC is different from many other tumor types and its unique treatment challenges. Both Drs are investigators in the phase 1b/2a study with fostrox in combination with Lenvima and will also share their perspectives from the ongoing study. They will be joined by Dr Pia Baumann, Medivir’s CMO who will provide an update on the ongoing study and fostrox development plans.

All three will be available to answer questions following the formal presentations.

The webcast will be streamed via a link on the website: www.medivir.com/investors/presentations The presentation will be available on Medivir´s website after the webcast.

– "The promising observations we have seen so far in the ongoing phase 1b/2a study of fostrox in combination with Lenvima mean that we are further intensifying our plans for the next phase of clinical development of fostrox. When doing so, it is critical that this is done in close collaboration with external experts to ensure that the specific needs of the disease and changes in treatment landscape are central components of future plans. We are pleased that Drs Evans and Reig, members of our Scientific Advisory Council, are able to provide their expertise on these important topics in this webcast," says Dr. Pia Baumann, CMO at Medivir.

Dr. Jeff Evans is a Professor of Translational Cancer Research in the School of Cancer Sciences, University of Glasgow, and Honorary Consultant in Medical Oncology at the Beatson West of Scotland Cancer Centre, Glasgow, UK. He is the Lead of the Glasgow Experimental Cancer Medicine Centre (ECMC) and National Clinical Lead of the NHS Scotland Cancer Research Network. He is an investigator in the fostrox clinical development program.

Dr. Maria Reig is the Head of the BCLC and Liver Oncology Unit at Hospital Clinic of Barcelona in Spain. Her expertise and area of interest is the development of prognostic models for patients with liver cancer and evaluation of treatment options with special emphasis in systemic therapy as well as new research about immune modulation and cancer emergence after antiviral treatment. She is an investigator in the fostrox clinical program.

For additional information, please contact;
Magnus Christensen, CFO, Medivir AB
Telephone: +46 8 5468 3100
E-mail: [email protected]

About fostrox
Fostrox is a pro-drug designed to selectively treat liver cancers and to minimize side effects. It has the potential to become the first liver-targeted and orally administered drug for patients with HCC. Fostrox has completed a phase 1b monotherapy study, and a combination study in HCC currently ongoing.

About primary liver cancer
Primary liver cancer is the third leading cause of cancer-related deaths worldwide and hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. There are approximately 660,000 patients diagnosed with primary liver cancer per year globally and current five-year survival is less than 20 percent1). HCC is a heterogeneous disease with diverse etiologies, and lacks defining mutations observed in many other cancers. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.

On September 1, 2023 ABM Therapeutics, a clinical-stage biopharmaceutical company, reported that the first patient has been successfully dosed in its multicenter Phase I study of ABM-1310 in patients with relapsed and drug resistant primary malignant brain tumors in China (Press release, ABM Therapeutics, SEP 1, 2023, View Source [SID1234634846]). This is the second clinical study of ABM-1310 in China.

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ABM-1310, the company’s proprietary clinical candidate developed as a next-generation BRAF inhibitor and demonstrated superior properties in pre-clinical animal models for treating cancer brain metastases, is a selective, highly water-soluble, orally active, and brain-penetrant small molecule BRAF inhibitor. ABM has been carrying out 2 additional studies of ABM-1310 in patients with BRAF V600X mutated advanced solid tumors in several well-known cancer centers in the United States and China. The preliminary observation of the US Phase I trial was presented at ASCO (Free ASCO Whitepaper) 2023 Annual Meeting (View Source).

The newly opened study (NCT05892653) is a phase I, open-label, multicenter clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer efficacy of ABM-1310 in patients with BRAF V600X mutant relapsed and drug resistant primary malignant brain tumors, with the goal to determine the optimal/recommended dose for phase 2 studies.

"We are excited to start this new study of ABM-1310. Primary brain tumors represent over 100 different sub-types, and patients whose tumors carry a BRAF V600X mutation are one of the clusters. Although progress has been made in the treatment of patients with primary malignant brain tumors in recent years, there is still a highly unmet medical need for those with recurrent or drug resistant diseases", said Dr. Chen Chen, CEO of ABM Therapeutics, " We have 3 clinical studies of ABM-1310 ongoing in China and the United States. We will work with investigators and clinical sites to push forward the clinical development of ABM-1310, with the passion to bring the potential therapeutic benefits to patients."

"Due to unfavorable prognosis associated with most primary malignant brain tumors and the limited treatment options that are currently available, there is an imperative to explore new therapeutic approaches. ", said Dr. Zane Yang, CMO of ABM Therapeutics. "Since ABM-1310 exhibits higher water solubility, cellular and blood-brain barrier penetration capabilities, compared to other BRAF inhibitors in preclinical research, we expect that ABM-1310 will provide special clinical benefits for patients with central nervous system tumors harboring BRAF V600X mutation"

As a clinical-stage biotechnology company, ABM has got a broad and robust proprietary pipeline to construct a Brain-Penetrant Kinase Drug Development Platform (BPKddTM）. We look forward to working with international pharmaceutical companies and biotech companies from multiple perspectives and making our drugs to benefit more patients in the world.