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.

On June 2, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported that the study results for efficacy and safety of IBI305 (biosimilar of bevacizumab) compared with bevacizumab in advanced, first-line, non-squamous NSCLC patients (NCT02954172) were presented by poster at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) [Abstract #9095; Sunday, June 2, 8:00 AM – 11:00 AM CDT] (Press release, Innovent Biologics, JUN 2, 2019, View Source [SID1234536783]).

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As the top and most influential international oncology conference, ASCO (Free ASCO Whitepaper) Annual Meeting provides the most important platform for publishing and discussing cutting edge clinical studies. Under the theme "Caring for Every Patient, Learning from Every Patient", 2019 ASCO (Free ASCO Whitepaper) Annual Meeting has attracted numerous top oncologists, scholars, staff from regulatory and patient organizations to share the latest updates and achievements in clinical oncology, with the ultimate goal to help deliver more promising medicines and treatment options to cancer patients.

It is worth noting that more and more Chinese companies choose to participate and disclose their programs in ASCO (Free ASCO Whitepaper), showcasing the importance of emerging Chinese biotech industry. As a leading Chinese biotech company, Innovent will provide key result update of several clinical studies at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting. The results on the treatment of relapsed or refractory extranodal NK/T cell lymphoma (ORIENT-4) with sintilimab will be presented in an oral session, and key data from several other clinical studies will be presented by posters and other sessions.

IBI305 is a recombinant humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody developed by Innovent for the treatment of non-small cell lung cancer (NSCLC), colorectal cancer and other malignant tumors. Bevacizumab (marketed under the trade name Avastin in China) has been approved globally for the treatment of multiple types of malignant tumors including NSCLC and has a favorable safety and efficacy profile. In 2012, bevacizumab was approved in China. Despite the huge demand for effective cancer therapies, the adoption rate of bevacizumab is relatively low due to low affordability.

NCT02954172 study, led by Professor Li Zhang from Sun Yat-sen University Affiliated Cancer Hospital, is a multicenter, randomized, double-blind, parallel, active-controlled, Phase III study in China, evaluating the efficacy and safety of IBI305 (biosimilar product candidate of bevacizumab) compared with bevacizumab in advanced non-squamous NSCLC patients as first-line treatment with ORR as the primary endpoint.

Among 450 recruited patients in the NCT02954172 study, there are 224 patients in IBI305 cohort and 226 patients in bevacizumab cohort.

The ORRs, evaluated by the Independent Radiological Review Committee (IRRC) in the full analysis set (FAS), were 44.3% (98/221) for IBI305 and 46.4% (102/220) for bevacizumab; the relative risk (RR) for ORR was 0.95 (90% CI: 0.803, 1.135).
The median progression free survival (PFS) was 7.9 months for IBI305 and 7.8 months for bevacizumab and duration of response (DoR) was also similar in both arms.
Treatment-emergent adverse events (TEAEs) were well balanced between treatment arms and consistent with the known adverse event profile of reference bevacizumab.
Based the outcome of the study, the new drug application (NDA) of IBI305 was accepted by the NMPA in January 2019 and has been granted priority review status.

Innovent intends to introduce a more affordable, high-quality biosimilar of bevacizumab to reach more patients in China and to further relieve their disease burden, benefiting more patients and their families.

About IBI305 (bevacizumab biosimilar)

IBI305 is a biosimilar product candidate of bevacizumab and a recombinant humanized anti-VEGF monoclonal antibody for injection. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF selectively with high affinity and blocks its binding to VEGF receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. Bevacizumab produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. The new drug application (NDA) of IBI305 was accepted by the NMPA on January 29, 2019 and has been granted with priority review status.

On June 2, 2019 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported data from its Phase II clinical trial (BGBC008, NCT03184571) with bemcentinib and Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced non-small cell lung cancer (NSCLC) at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois (31 May – 4 June 2019) (Press release, BerGenBio, JUN 2, 2019, View Source;median-survival-rates-in-phase-ii-trial-with-bemcentinib-and-keytruda-in-pts-with-advanced-nsclc-at-asco-2019-300860276.html [SID1234536784]).

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At data cut off, 35 out of 46 enrolled patients were evaluable; 58% were AXL +ve, and 53% were PD-L1 negative (<1%TPS), and a further 39% were PD-L1 (1-49% TPS). An objective response rate of 40% was achieved in AXL +ve patients, irrespective of the patients PD-L1 score; and an overall response rate of 29% was achieved. The median survival rate of 12.2 months was observed at the time of data cut-off, significantly surpassing what has been shown historically in second line treatment with PD-1 inhibitor monotherapy.

The combination treatment of bemcentinib and pembrolizumab was overall well-tolerated; the most common adverse events included transaminase increase (35%), fatigue (30%), and diarrhoea (26%). No grade 5 treatment related adverse events were reported and all events were reversible.

Principal investigator Enriqueta Filip, Vall d’Hebron University Hospital, Barcelona: "Following the rapid uptake of checkpoint inhibitors in first-line lung cancer therapy, treatment options for NSCLC cancer patients that have not responded to anti-PD-1 therapies such as KEYTRUDA represent a significant unmet medical need. These data, which suggest that combination therapy with bemcentinib has the potential to enhance patient responses to these novel agents, particularly in patients with no or limited expression of PD-L1, is a very significant and encouraging development."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "The clinical activity we are presenting here today surpasses what has been shown historically in previously-treated, PD-L1 low patients on PD-1 inhibitor monotherapy, and supports the hypothesis that AXL is implicated in the failure of anti-PD-L1 therapies. Further investigation is warranted and having recently extended the trial to include patients showing disease progression on checkpoint inhibitors, we will continue to test this hypothesis and look forward to providing further updates during 2019."

About NSCLC

It is estimated that more than 230,000 new cases of lung cancer have been diagnosed in the US in 2018 and it is the leading cause of cancer deaths. 65% of non-small cell lung cancers (NSCLC) are of adenocarcinoma pathology. Although various treatments exist for NSCLC, they are often curtailed by acquired resistance to therapy and immune evasion. Novel treatments overcoming these mechanisms in NSCLC are urgently required.

About the BGBC008 trial

The BGBC008 trial is a Phase II open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated patients with advanced adenocarcinoma of the lung, run at centres in the US, UK, Spain and Norway. The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

Patients eligible for participation in Cohort A must have progressed on or after prior therapy excluding immunotherapy whereas patients in Cohort B will be actively progressing on a therapy regimen containing an anti-PD(L)-1 therapy.

Both cohorts follow a two-stage design, Cohort A has previously successfully progressed into the second stage after meeting its first efficacy endpoint. Cohort B will evaluate advancement into stage 2 after 13 patients have been assessed for response.

For more information please access trial NCT03184571 at www.clinicaltrials.gov.