On January 25, 2021 AstraZeneca reported that Positive high-level results from the ELEVATE-RR Phase III trial showed Calquence (acalabrutinib) met the primary endpoint demonstrating non-inferior progression-free survival (PFS) for adults with previously treated, high-risk chronic lymphocytic leukaemia (CLL) compared to ibrutinib (Press release, AstraZeneca, JAN 25, 2021, View Source [SID1234574250]).

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The trial also met a key secondary endpoint for safety, showing patients treated with Calquence had statistically significantly lower incidence of atrial fibrillation compared to patients treated with ibrutinib. Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.1 Further hierarchical testing revealed no difference for Grade 3 or higher infections or Richter’s transformation. There was a descriptive trend for numerically favourable overall survival. Overall, the safety and tolerability of Calquence were consistent with the profile seen in the broader Calquence clinical development programme.

ELEVATE-RR is the first Phase III trial to compare two Bruton’s tyrosine kinase (BTK) inhibitors in patients with CLL, the most common type of leukaemia in adults.2 Patients diagnosed with high-risk CLL may experience rapid worsening of their disease, requiring treatment.3

José Baselga, Executive Vice President, Oncology R&D, said: "With over forty months of follow-up, today’s results confirm that Calquence, a selective BTK inhibitor, displays superior safety in atrial fibrillation without compromising efficacy. The totality of the data confirm our confidence in the favourable benefit-risk profile of Calquence."

The data will be presented at a forthcoming medical meeting and shared with health authorities.

CLL
CLL is the most common type of leukaemia in adults, with an estimated 114,000 new cases globally in 2017, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.2,4-6 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

ELEVATE-RR
ELEVATE-RR (ACE-CL-006) is a randomised, multicentre, open-label Phase III non-inferiority trial of Calquence versus ibrutinib in patients with previously treated CLL with high-risk features (presence of 17p deletion and/or 11q deletion). In the trial, 533 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence (100mg orally twice daily) until disease progression or unacceptable toxicity. Patients in the second arm received ibrutinib (420mg orally once daily) until disease progression or unacceptable toxicity.7

The primary endpoint for the trial was PFS assessed by an independent review committee (non-inferiority; tested after 250 events). Secondary endpoints included incidence of atrial fibrillation, incidence of treatment-emergent Grade 3 or higher infections, incidence of Richter’s transformation (a condition in which CLL changes into an aggressive form of lymphoma) and overall survival.7

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.8,9 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.8

Calquence is approved for the treatment of CLL and small lymphocytic lymphoma in the US and approved for CLL in the EU and several other countries worldwide. Calquence is under regulatory review in Japan for relapsed or refractory CLL. A Phase I trial is currently underway in Japan for the treatment of 1st-line CLL.

In the US and several other countries, Calquence is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 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. Calquence is not currently approved for the treatment of MCL in Europe or Japan.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 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’s 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 medicines approved in the US 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 seven 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.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – 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 January 25, 2021 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported its financial results for the fiscal year ended October 31, 2020 and provides a business update (Press release, Advaxis, JAN 25, 2021, View Source [SID1234574249]).

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Fiscal Year 2020 and Recent Key Accomplishments:

Presented updated clinical data from the ongoing Phase 1/2 trial of ADXS-503 as a monotherapy and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in non-small cell lung cancer (NSCLC) at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting
In the Part B combination arm, reported disease control rate of 67% and overall response rate of 17% in first six evaluable patients with immediate prior progression on KEYTRUDA
Reported durable and sustained tumor control, with confirmed stable disease and a partial response lasting out to 10 months
Biomarker data across 9 patients across trial arms confirmed on-mechanism activation of innate and adaptive immune responses to ADXS-503 with activation of cytotoxic -and/or memory CD8+ T cells as well as 100% efficient priming by ADXS-503
Across trial arms, ADXS-503 appeared safe and well tolerated as a monotherapy and in combination with KEYTRUDA with no added toxicities from combination therapy
Initiated ADXS-503 Part B combination arm efficacy expansion which will enroll up to 15 patients to evaluate the potential of ADXS-503 in combination with KEYTRUDA to restore and/or enhance responsiveness to checkpoint inhibitors in PD-1/L-1 refractory NSCLC patients
Initiated ADXS-503 Part C combination arm to evaluate ADXS-503 in combination with KEYTRUDA as a first line treatment in patients with metastatic NSCLC that would receive KEYTRUDA alone as per label indication with PD-L1 expression ≥ 1% or who are unfit to receive the standard of care regimen of KEYTRUDA in combination with platinum based-chemotherapy
Announced FDA Clearance of new Investigational New Drug (IND) application for ADXS-504 for the treatment of prostate cancer at a leading medical institution
Announced common stock purchase agreement for up to $20 million of common stock with Lincoln Park Capital
Announced an at-the-market offering program for up to $40 million of common stock with A.G.P./Alliance Global Partners, as sales agent
Announced closing of $9.2 million public offering of common stock and warrants, with proceeds being used to fund continued development and expansion of our product pipeline, including investment in our ADXS-HOT program and for general corporate purposes
Cash runway currently anticipated to take the Company into fiscal second quarter of 2022
Management Commentary

"Fiscal year 2020 was transformative for Advaxis, with important clinical and biomarker data from the ongoing Phase 1/2 study of ADXS-503 in NSCLC which now consistently show the potential of ADXS-503 to synergistically enhance and/or restore sensitivity to checkpoint inhibitors," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Based on these encouraging results, we have prioritized this study, beginning enrollment in the expansion of Part B to further evaluate the promising signals of sustained clinical benefit observed in Part B in NSCLC patients with immediate prior progression on KEYTRUDA, as well as Part C, which will evaluate ADXS-503 in combination with KEYTRUDA in the first line setting. We remain confident that our clinical strategy will explore the full potential of ADXS-503 to improve responses to checkpoint inhibitors across diverse clinical settings and patient populations, and are highly enthusiastic about the on-mechanism innate and adaptive immune stimulation seen in our broadly accessible, off-the-shelf neoantigen immunotherapy. In addition to these encouraging data, our strengthened balance sheet ensures our continued momentum with the ADXS-HOT program as we advance our Lm-technology to expand the reach of checkpoint inhibitors."

Balance Sheet Highlights

As of October 31, 2020, Advaxis had cash and cash equivalents of $25.2 million. The Company used $21.9 million in cash to fund operations during fiscal year 2020, mainly attributed to funding research and development and general and administrative activities. Throughout fiscal year 2020, the Company continued to prioritize its strategic pipeline across all programs and reduced its annual operating expenses by approximately $12.2 million, or nearly 31%.

Fiscal Year 2020 Financial Information
Research and development expenses for fiscal year 2020 were $15.6 million, compared with $26.7 million for fiscal year 2019. The $11.1 million decrease was primarily attributable to decreases in clinical trial costs, laboratory costs, drug manufacturing process validation and drug stability studies.

General and administrative expenses for fiscal year 2020 were $11.1 million, compared to $12.2 million for fiscal year 2019.

The net loss for the fiscal year ended October 31, 2020 was $26.5 million or $0.43 per share based on about 61 million weighted average shares outstanding. This compares with a net loss for fiscal year 2019 of $16.6 million or $1.09 per share based on 15.2 million weighted average shares outstanding.

On January 25, 2021 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained approval from the Ministry of Health, Labour and Welfare (MHLW) on January 22, 2021 for the expanded use of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic (CDx) for the tropomyosin receptor kinase (TRK) inhibitor, larotrectinib developed for the treatment of patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, also known as TRK fusion cancer (Press release, Chugai, JAN 25, 2021, View Source [SID1234574246]).

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"Chugai aims to advance personalized healthcare and it is an important step for us that FoundationOne CDx Cancer Genome Profile received approval as a companion diagnostic for larotrectinib, which was developed for the treatment of cancer patients with an NTRK gene fusion, a rare genomic alteration," said Dr. Osamu Okuda, Chugai’s President and COO. "We are committed to broaden the adaptation of this genomic profiling so that as many patients as possible can receive the appropriate treatment for the disease."

This approval expands the use of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic to identify patients with TRK fusion cancer who could benefit from treatment with larotrectinib. The efficacy and safety of larotrectinib were investigated in the multiple clinical trials conducted by Bayer; a phase I trial in adult patients, the phase II NAVIGATE trial in adult and adolescent patients, and the phase I/II pediatric SCOUT trial. Bayer Yakuhin, Ltd. submitted an application for marketing authorization of larotrectinib for the treatment of patients with solid tumors harboring an NTRK gene fusion to the MHLW on May 22, 2020.

As a leading company in the field of oncology, Chugai is committed to advancing personalized oncology care and contribute to patients and healthcare professionals through improving access to comprehensive genomic profiling of cancers.

Approval information The underlined part has been newly added.

Intended uses or indications

The Product is used for comprehensive genomic profiling of tumor tissues in patients with solid cancers.
The Product is used for detecting gene mutations and other alterations to support the assessment of drug indications listed in the table below.
Alterations Cancer type Relevant drugs
Activated EGFR alterations Non-small cell lung cancer (NSCLC) afatinib dimaleate, erlotinib hydrochloride, gefitinib, osimertinib mesylate
EGFR exon 20 T790M alterations osimertinib mesylate
ALK fusion genes alectinib hydrochloride, crizotinib, ceritinib
ROS1 fusion genes entrectinib
MET exon 14 skipping alterations capmatinib hydrochloride hydrate
BRAF V600E and V600K alterations Malignant melanoma dabrafenib mesylate, trametinib dimethyl sulfoxide, vemurafenib
ERBB2 copy number alterations (HER2 gene amplification positive) Breast cancer trastuzumab (genetical recombination)
KRAS/NRAS wild-type Colorectal cancer cetuximab (genetical recombination), panitumumab (genetical recombination)
NTRK1/2/3 fusion gene Solid tumors entrectinib, larotrectinib sulfate
BRCA1/2 alterations Ovarian cancer olaparib
BRCA1/2 alterations Prostate cancer olaparib
About FoundationOne CDx Cancer Genomic Profile
Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. The program is available as a companion diagnostic for multiple molecular-targeted drugs approved in Japan.

About larotrectinib
Larotrectinib, an oral selective TRK inhibitor, was exclusively designed to treat tumors that have an NTRK gene fusion. Larotrectinib was granted Orphan Drug Designation by the Ministry of Health, Labour and Welfare for the expected indication of "Locally advanced or metastatic solid tumor harboring an NTRK gene fusion."

On January 23, 2021 Scandion Oncology A/S ("Scandion" or the "Company") reported it has completed the first 12 patient cohort in the ongoing dose-range finding part of the clinical phase II study with SCO-101 in combination with chemotherapy (FOLFIRI) in patients with drug resistant metastatic colorectal cancer (Press release, Scandion Oncology, JAN 23, 2021, View Source,c3272887 [SID1234574546]). The Company has now received green light from the Data Safety Monitoring Board to move forward with the next treatment cohorts.

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In this first cohort from the CORIST study, all patients received combination treatment with SCO-101 and the chemotherapy regime FOLFIRI. The cohort was utilized to stepwise adjust the dose of chemotherapy when given together with a fixed dose of SCO-101.

First cohort has added significant understanding

CMO Peter Michael Vestlev: "The CORIST study is our first clinical study where SCO-101 is combined with chemotherapy in drug resistant cancer patients who have no further treatment options. The data has added significant understanding of how to proceed with the SCO-101 treatment. I am looking forward to the next cohorts and to perform the second part of this phase II clinical study."

Timeline maintained, readout expected in Q2, 2021

CEO Bo Rode Hansen: "Our clinical team together with the clinical investigators have done a great job in recruiting this many patients within a short time frame despite the COVID-19 situation. We maintain our expectation of a readout in Q2, 2021 from this first part of the CORIST study."

This information is information that Scandion Oncology A/S is obliged to publish in accordance with the EU Market Abuse Regulation. The information was provided by the contact person above for publication on 23 January 2021.

On January 22 , 2021 PharmCAD, an artificial intelligence ( AI )-based new drug development company, reported that it signed a joint development agreement with Kainogen to develop and commercialize a new anticancer drug (Press release, PharmCADD, JAN 22, 2021, View Source [SID1234644206]).

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With this contract, PharmCAD plans to use the new drug development platform ‘Pharmulator’ to discover anticancer drug candidates optimized for Kainogen’s target proteins within 20 weeks and provide them to Kainogen. Kainogen will synthesize substances and conduct clinical trials.

Pharmulator is a new drug development platform that combines AI , physics, chemistry, and bioinformatics. It consists of modules for protein 3D structure prediction, molecular dynamics simulation, quantum calculation, toxicity prediction, and new drug creation. Through the combination of these modules, candidate substances with a high probability of success as a new drug can be derived.

Kainogen is a company developing a next-generation anti-cancer technology platform based on immunosynapse and immunometabolism technologies that strengthen the bond between cancer cells and immune cells.

Kainogen CEO Moon Ji-young said, "Through the joint development agreement, we will be able to further accelerate the speed of research and development of not only the immune anti-cancer drug pipeline that we are pursuing, but also the metabolic anti-cancer drug pipeline."

Taehyung Kwon, CEO of PharmCAD, said, "Through the joint development agreement with Kainogen, which is focusing on developing next-generation anticancer technology, we will be able to further strengthen the technological scalability and reliability of PharmCAD’s new drug development platform ‘Pamulator.’"