On June 3, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that the final progression-free survival (PFS) data and the second interim analysis of overall survival (OS) from the Japanese phase III J-ALEX study for Alecensa were presented on June 2 (local time) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place from May 31 to June 4 in Chicago, IL, United States (Press release, Chugai, JUN 3, 2019, View Source [SID1234536782]). J-ALEX study compared Alecensa and crizotinib as the first-line treatment for patients with ALK fusion gene positive non-small cell lung cancer (NSCLC).

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Abstract #9092;
Final PFS analysis and safety data from the phase III J-ALEX study of Alectinib (ALC) vs. Crizotinib (CRZ) in ALK-inhibitor naïve ALK-positive Non-Small Cell Lung Cancer (ALK+NSCLC)

"The long-term data from the J-ALEX study confirms the benefits of Alecensa as the first-line treatment for patients with ALK-positive NSCLC," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit.

The J-ALEX study is an open-label, randomized phase III study that compares the efficacy and safety between Alecensa and crizotinib. The J-ALEX study enrolled 207 ALK-inhibitor naïve patients with ALK fusion gene positive advanced or recurrent NSCLC, who either had not undergone chemotherapy or had undergone one chemotherapy regimen. The primary endpoint of the J-ALEX study was PFS as assessed by an independent review facility (IRF). The secondary endpoints included OS, time to disease progression of brain metastases in patients with brain metastases at baseline, and safety.

In February, 2016, Chugai carried out a prospectively defined interim analysis, and had an independent data monitoring committee examine the results. Since the results showed that Alecensa significantly prolonged PFS to a higher extent than anticipated, the committee decided to recommend an early discontinuation of the study [Alecensa arm: not estimable (95% CI: 20.3-not estimable), crizotinib arm: 10.2 months (95% CI: 8.2-12.0), HR=0.34 (99.7% CI: 0.17-0.70), stratified log-rank test, p<0.0001)].

Latest data from the J-ALEX study shows:

Risk of progression or death was reduced by 63% (HR=0.37, 95% CI: 0.26-0.52) in the Alecensa arm compared to the crizotinib arm. Median PFS (primary endpoint) was 34.1 months in the Alecensa arm (95% CI: 22.1-not estimable) versus 10.2 months (95% CI: 8.3-12.0) in the crizotinib arm.
In the second interim analysis, the superiority of OS in the Alecensa arm over the crizotinib arm was not conclusive (stratified HR=0.80, 95% CI: 0.35-1.82). The investigation on OS will be continued.
The safety profile of Alecensa was consistent with previous reports.
[Reference information]
Media release issued by Chugai on May 11, 2017:
Results of the J-ALEX Study for Chugai’s Alecensa are Published in "The Lancet" Online;
View Source

On June 3, 2019 BerGenBio ASA (OSE:BGBIO) reported data showing significant efficacy in Phase II clinical trials (BGBC003, NCT02488408) evaluating bemcentinib, a first-in-class selective oral AXL inhibitor, in combination with low-dose cytarabine (LDAC) or decitabine as a potential new treatment regimen for acute myeloid leukaemia (AML) patients unable to tolerate intensive therapy (Press release, BerGenBio, JUN 3, 2019, View Source [SID1234536799]). The data will be presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Chicago, Illinois (31 May – 4 June 2019).

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In total, 33 patients were enrolled into the trial: 16 into the LDAC + bemcentinib group, of which 13 are evaluable for efficacy to date, and 17 into the decitabine + bemcentinib group, of which 12 are evaluable for efficacy to date.

Among the 13 evaluable patients in the LDAC + bemcentinib group, 6 responses have been reported; 4 patients achieved complete remission / complete remission with incomplete hematologic recovery (CR/CRi) and 2 patients’ partial remission (PR). This yields an overall response rate (ORR) of 46%, including 31% CR/CRi among elderly AML patients (>70 years). Furthermore, one patient achieved durable stable disease for more than 3 months. The relapse free survival rate (RFS) for patients with CR/CRi is 6.2 months (0.7 to 9.6 months); data immature.

In the decitabine/bemcentinib group, of the 12 evaluable patients, 3 responses have been reported; 1 patient achieved CR/CRi and 2 patients PR. This yields an ORR of 25%. Furthermore, five patients had durable stable disease for more than 3 months. The RFS for patients with CR/CRi is 5 months; data immature.

The combination treatment of bemcentinib and LDAC or decitabine was overall well-tolerated; the most common adverse events (>15% of patients) included anaemia, neutropenia and diarrhoea. No grade 5 TRAEs were reported and all events were reversible.

Professor Sonja Loges, attending physician and principal investigator, University Medical Centre Hamburg Eppendorf, Germany commented: "These early results are very encouraging, particularly as we have seen responses in a less fit AML patient population with comparatively poor prognosis [having not responded to first-line therapies], or with high risk cytogenetics. These data show that bemcentinib in combination with LDAC resulted in a significantly higher ORR than previously observed/historical benchmarks in single-agent cytarabine. These early results warrant further investigation of bemcentinib in a larger trial addressing AML patients unfit for intensive chemotherapy."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "A majority of AML patients are unable to tolerate intensive chemotherapy and have limited treatment options, particularly if established first-line therapies fail. These combination trials of bemcentinib with low-dose cytarabine and decitabine show promising results that the addition of our selective AXL inhibitor will improve the outcome of treatment with these much-used agents. Although these are early findings, we are encouraged by the emerging clinical data and focused on advancing our late stage development programme."

– END –

About AML and the BGBC003 trial
Acute myeloid leukaemia (AML) is a rapidly progressing blood cancer. AML is the most common form of acute leukaemia in adults, where malignant AML blasts interfere with the normal functioning of the bone marrow leading to a multitude of complications like anaemia, infections and bleeding. AML is diagnosed in over 20,000 patients in the US annually and is rapidly lethal if left untreated. Successful treatment typically requires intensive therapy or bone marrow transplantation, and relapse and resistance are common. Consequently, there is an urgent need for effective novel therapies in relapsed/refractory patients, particularly those that are ineligible for intensive therapy or bone marrow transplant.

The BGBC003 trial is a phase Ib/II multi-centre open label study of bemcentinib in combination with cytarabine (part B2) and decitabine (part B3) in patients with AML who are unsuitable for intensive chemotherapy as a result of advanced age or existing-co-morbidities. Up to 28 patients will be enrolled at centres in the US, Norway, Germany and Italy.

For more information please access trial NCT02488408 at www.clinicaltrials.gov.

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

On June 3, 2019 VBL Therapeutics (Nasdaq: VBLT) reported the presentation of the final results from a Phase 1/2 clinical trial of VB-111 in the treatment of patients with recurrent platinum resistant ovarian cancer on Saturday, June 1st at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, in Chicago (Press release, VBL Therapeutics, JUN 3, 2019, View Source [SID1234536817]).

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Data demonstrated a median overall survival (OS) of 498 days in the VB-111 therapeutic-dose arm, versus 172.5 days in the low-dose arm (p=0.03). 58% of evaluable patients treated with the therapeutic dose of VB-111 had a GCIG CA-125 response. In comparison, in the AURELIA trial, the GCIG CA-125 response rate was 31.8% with bevacizumab and chemotherapy, and only 11.6% with chemotherapy alone.

VB-111 activity signals were seen despite unfavorable prognostic characteristics (50% platinum refractory disease and 50% previous treatment with anti-angiogenics). There was a trend for favorable survival in patients who had CA-125 decrease >50% in the VB-111 therapeutic-dose arm (808 vs. 351 days; p=0.067) implicating CA-125 as a valuable biomarker for response to VB-111. Post treatment fever was also associated with a signal for improved survival (808 vs. 479 days; p=0.27).

"The improved overall survival seen with the therapeutic dose of VB-111 is compelling, given that this trial focused on women with poor prognosis whose disease had progressed following several lines of prior therapies," said Tami Rachmilewitz, M.D., Vice President Clinical Development of VBL Therapeutics. "The high CA-125 response rate, the long duration of responses and the recruitment of immune cells into the tumor provide additional evidence for activity of VB-111, and support its continued development in ovarian cancer."

"These data reinforce our confidence in VB-111 as we continue to advance OVAL, our potential registration trial in platinum resistant ovarian cancer," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. "Importantly, the data implicating CA-125 decrease as a biomarker for VB-111 activity can be valuable for our Phase 3 OVAL trial, for which an interim analysis is expected around year-end 2019. In addition, the ability of VB-111 to turn a notoriously `cold` tumor like ovarian cancer `hot` is suggestive that VB-111 may have broader applicability across additional cold tumors. We look forward to the launch of investigator-sponsored trials in rGBM and colon cancer to provide more data on the potential of VB-111."

For additional information see: ASCO (Free ASCO Whitepaper) poster

About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in the OVAL potential-registration Phase 3 pivotal trial for ovarian cancer (ClinicalTrials.gov Identifier: NCT03398655). VB-111 has received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. In addition, VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970). VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission.

On June 3, 2019 GeneCentric Therapeutics reported that it will present the first data on novel response signatures for metastatic, muscle invasive bladder cancer (MIBC) treatments by applying its proprietary, RNA-sequencing based predictive response signature and Cancer Subtyping Platform (CSP) (Press release, GeneCentric Therapeutics, JUN 3, 2019, View Source [SID1234536836]). The initial response signature and MIBC cohort data are being presented at a poster session at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL, later today.

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"MIBC remains a significant area of unmet need for patients, with a median 5-year survival rate of 5 percent," said Dr. Mike Milburn, CEO/President of GeneCentric and senior author on the study. "The advent of immune checkpoint inhibitors (ICP) offers further treatment options in MIBC, however, their clinical benefit varies considerably by patient. We are excited to be at the forefront of advancing such gene response signatures for the benefit of patients."

The overall goal of the study, conducted by GeneCentric scientists in collaboration with researchers at the University of North Carolina Chapel Hill’s Lineberger Cancer Center, is to assess the genomic characteristics of MIBC patients treated with ICPs and to assess the potential implications of those characteristics on treatment responses and outcomes. The study involves applying the Company’s 60-gene 4-class MIBC expression subtyper (BCSP) and an initial FGFR3 activation response signature, developed from MIBC TCGA (The Cancer Genome Atlas) data along with other proprietary assays, to a cohort of de-identified MIBC patients who underwent prior ICP. To stratify and identify positive or negative ICP response indicators, comprehensive genomic analyses were performed on archived FFPE samples from patients within this cohort, followed by tumor and immune profiling as well as subtype and other response associated predictor analyses. The full analysis of the complete dataset (n=97) will be presented at a future meeting.

Details of the presentation are as follows:

Title: "RNAseq and DNA Whole-Exome Sequence Analysis Reveal Novel Response Signatures to IO Treatment in Muscle Invasive Bladder Cancer (MIBC) Patients."

Abstract Number: 4558

Date: June 3, 2019

Time: 1:15 PM to 4:15 PM

Location: Hall A

Presenter: Greg Mayhew, PhD, Director, Bioinformatics, GeneCentric Therapeutics

To read the abstract, please visit: View Source

On June 3, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has launched FoundationOne CDx Cancer Genomic Profile, (hereafter "the Program") a next-generation sequencing based gene mutation analysis program (Press release, Chugai, JUN 3, 2019, View Source [SID1234536853]). Also, SRL Inc. has started providing testing services for the Program today.

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FoundationOne CDx is the first cancer genomic test in Japan which obtained regulatory approval for the two functions of gene mutation analysis program (for use in cancer genome profiling) for solid tumors, and somatic gene mutation analysis program (for use in assessing anticancer drug indications). The approval was granted by the Ministry of Health, Labour and Welfare on December 27, 2018.

"FoundationOne CDx Cancer Genomic Profile will open up a new horizon for personalized cancer care. I am delighted that the program is now available for patients and healthcare providers in Japan," said Tatsuro Kosaka, Chugai’s President and CEO. "Through this program, Chugai will further strive to realize advanced and sustainable patient-centric healthcare by promoting access to treatments optimized to each patient."

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection and analysis 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 patient’s tumor tissues. As a comprehensive companion diagnostic function, it can be also used as a companion diagnostic for certain molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare providers through comprehensive genomic profiling.

[Notes]
A press release issued on March 19, 2019: Miraca and Chugai Enter into Business Partnership Agreement for "FoundationOne CDx Cancer Genome Profile"
View Source

Approval information

Brand name FoundationOne CDx Cancer Genomic Profile
Nonproprietary name
Gene mutation analysis program (for use in cancer genome profiling)
Somatic gene mutation analysis program (for use in assessing anticancer drug indications)
Approval date December 27, 2018
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
EGFR exon 19 deletions and EGFR exon 21 L858R 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
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)
Conditions for approval
The necessary measures must be taken to ensure that the product is used by a physician with adequate knowledge and experience of cancer genomic medicine at a medical institution with a cancer genome profiling-based medical system pursuant to the "Guidelines for the Development of Core Hospitals and Other Facilities for Cancer Genomic Medicine," and in compliance with the scope and timing of testing stipulated in the most recent guidelines, etc., of relevant academic societies.
Appropriate procedures and controls to protect personal information and up-to-date security and privacy protection measures to prevent unauthorized access must be implemented for tumor tissue specimens sent to the laboratory and for information obtained from these specimens.
Quality control of input data must be performed as described in the Remarks column of the attached Application Form. Any changes to the quality control of input data as described in the Remarks column of the Application Form (excluding minor changes specified by Order of the MHLW in Article 23-2-5, paragraph (11) of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices ["the Act"]) must be approved by the MHLW Minister pursuant to Article 23-2-5, paragraph (11) of the Act. Note that this approval applies mutatis mutandis to the provisions of Article 23-2-5 paragraph (13), Article 23-2-6, and Article 23-2-7 of the Act.