On September 10, 2019 GSK reported that data from its growing oncology pipeline will be presented at the in European Society for Medical Oncology Congress Barcelona, Spain, September 27 – October 01, 2019 (Press release, GlaxoSmithKline, SEP 10, 2019, View Source [SID1234539397]). Data spans nine tumour types, including ovarian and head and neck cancers, and highlight a diverse portfolio of potentially transformational medicines for cancer patients in immuno-oncology, cancer epigenetics, cell therapy and synthetic lethality.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results from the Phase 3 PRIMA (ENGOT-OV26/GOG-3012) study of Zejula (niraparib) maintenance treatment for patients with newly diagnosed advanced ovarian cancer will be presented in a Presidential Symposium. In July, positive headline results from the study demonstrated that niraparib could benefit women in the first line maintenance setting independent of biomarker status in a statistically significant and clinically meaningful way, with a safety and tolerability profile consistent with previous clinical trials. Niraparib is not currently approved by regulators in this indication.

"Our presentations at ESMO (Free ESMO Whitepaper) represent the first wave of data across the four focus areas of our new oncology pipeline and show the significant progress we have made in accelerating these potentially transformational medicines," said Dr. Axel Hoos, Senior Vice President and Head Oncology R&D. "We are particularly pleased with the promising data from our late-breaking PRIMA study, which enrolled women with first-line ovarian cancer who were at high risk for recurrence."

Data being presented at ESMO (Free ESMO Whitepaper) include:

Zejula (niraparib)

Niraparib Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer (PRIMA/ENGOT-OV26/GOG 3012)
A Gonzalez, #LBA1, Sep 28, 2019, 16:30 – 18:20, Barcelona Auditorium (Hall 2)
Immune-Related Gene Expression Profiling after Neoadjuvant Chemotherapy (NACT) of Ovarian High-Grade Serous Carcinoma
L M Manso, #1017P, Sep 29, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Clinical Confirmation of Higher Exposure to Niraparib in Tumor vs Plasma in Patients With Breast Cancer
L Spring, #211P, Sep 29, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Evaluation of Niraparib 200 mg/d as Maintenance Therapy in Recurrent Ovarian Cancer and Associated Thrombocytopenia in a Real-World US Setting
P Thaker, #1005P, Sep 29, 2019, 12:00 – 13:00, Poster Area (Hall 4)
GSK3359609: ICOS

Inducible T cell co-stimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and combination with pembrolizumab (pembro): preliminary results from INDUCE-1 expansion cohorts in head and neck squamous cell carcinoma (HNSCC)
D Rischin, #1119PD, Sep 28, 2019, 08:45 – 09:45, Bilbao Auditorium (Hall 5)
Pharmacokinetic/pharmacodynamic (PK/PD) exposure-response characterization of the ICOS agonist mAb GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
M Maio, #1971P, Sep 30, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Belantamab mafodotin: BCMA

Trials in progress: DREAMM 4: A phase I/II single arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
S Trudel, #1105TiP, Sep 28, 2019, 12:00 – 13:00, Poster Area (Hall 4)
GSK3326595: PRMT5

METEOR-1: A Phase I Study of GSK3326595, a First-In-Class Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Advanced Solid Tumors
L Siu, #438O, Sep 29, 2019, 16:30 – 18:00, Malaga Auditorium (Hall 5)
GSK3377794: NY-ESO-1

Epidemiology of synovial sarcoma in EU28 countries
N Joseph, #1728P, Sep 28, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Trials in progress: Safety and tolerability of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non-small cell lung cancer: A phase 1b/2a randomized pilot study
K L Reckamp, #1590TiP, Sep 28, 2019, 12:00 – 13:00, Poster Area (Hall 4)
NY-ESO-1 and LAGE1A – an emerging target for cell therapies in solid tumours
I Eleftheriadou, #1229P, Sep 30, 2019, 12:00 – 13:00, Poster Area (Hall 4)
GSK1795091: TLR4

Trial in progress: A phase I, open-label study of GSK1795091 administered in combination with immunotherapies in participants with advanced solid tumors
A R Hansen, #511TiP, Sep 28, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Bintrafusp alfa (M7824):

Trials in Progress: Bintrafusp alfa (M7824) and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer (TNBC)(NCT03579472)
J Litton, 383TiP, Sep 29, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Alliances with ZEJULA (niraparib)

A Prospective Evaluation of Tolerability Of Niraparib Dosing Based on Baseline Body Weight (BW) and Platelet (Plt) Count: Blinded Pooled Interim Safety Data from the NORA Study
X Wu, #1004P, Sep 29, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Trials in progress: A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641)
K Chi, #897TiP, Sep 30, 2019, 12:00 – 13:00, Poster Area (Hall 4)
Pre-specified interim analysis of GALAHAD: A phase 2 study of niraparib in patients with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD)
M R Smith, #LBA50, Sep 29, 2019, 8:30 – 9:45, Malaga Auditorium (Hall 5)
Indication and Usage for ZEJULA

ZEJULA is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Important Safety Information for ZEJULA

Myelodysplastic Syndrome/Acute Myeloid Leukaemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anaemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anaemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anaemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. Do not start ZEJULA until patients have recovered from haematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically thereafter. If haematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a haematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Based on its mechanism of action, ZEJULA can cause foetal harm. Advise females of reproductive potential of the potential risk to a foetus and to use effective contraception during treatment and for 6 months after receiving their final dose. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anaemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhoea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnoea (20%), cough (16%), rash (21%) and hypertension (20%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in haemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

GSK in Oncology

GSK is focused on maximizing patient survival through transformational medicines for people living with cancer. GSK’s pipeline is focused on immuno-oncology, cell therapy, synthetic lethality and cancer epigenetics. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On September 10, 2019 University of California, reported the U.S. Patent and Trademark Office (USPTO) granted a new CRISPR-Cas9 patent to the University of California (UC), University of Vienna, and Dr. Emmanuelle Charpentier covering single-molecule guide RNAs or nucleic acid molecules encoding the guide RNAs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Today’s patent (U.S. 10,407,697) is the 13th in the university’s U.S. CRISPR-Cas9 portfolio and follows the issuance of 10 other patents in the past six months. Continuing the momentum into the fall, UC expects to further expand its portfolio through the issuance of four additional patents in the near future. In total, the patents that have issued and those that are set to issue bring the university’s portfolio to 17 U.S. CRISPR-Cas9 patents covering various compositions and methods of targeting and editing genes in any setting, such as within plant, animal, and human cells, as well as modulating transcription.

"We are pleased by our recent trajectory that has significantly increased UC’s intellectual property protection of the Doudna-Charpentier team’s work on CRISPR-Cas9," said Eldora L. Ellison, Ph.D., lead patent strategist on CRISPR-Cas9 matters for UC and a Director at Sterne, Kessler, Goldstein & Fox. "We will continue pursuing claims for this pioneering gene-editing technology so we can ensure the methods are utilized for the benefit of society."

The Doudna-Charpentier team that invented the CRISPR-Cas9 DNA-targeting technology included Jennifer Doudna and Martin Jinek at the University of California, Berkeley; Emmanuelle Charpentier (then of Umea University); and Krzysztof Chylinski at the University of Vienna. The single-molecule guide RNAs covered by today’s patent, as well as the other compositions and methods claimed in UC’s previously issued patents and those set to issue, were included among the CRISPR-Cas9 gene editing technology work disclosed first by the Doudna-Charpentier team in its May 25, 2012 priority patent application.

Additional CRISPR-Cas9 patents in this team’s portfolio include 10,000,772; 10,113,167; 10,227,611; 10,266,850; 10,301,651; 10,308,961; 10,337,029; 10,351,878; 10,358,658; 10,358,659; 10,385,360; and 10,400,253. These patents are not a part of the PTAB’s recently declared interference between 14 UC patent applications and multiple previously issued Broad Institute patents and one application, which jeopardizes essentially all of the Broad’s CRISPR patents involving eukaryotic cells.

International patent offices have also recognized the pioneering innovations of the Doudna-Charpentier team, in addition to the 13 patents granted in the U.S. so far. The European Patent Office (representing more than 30 countries), as well as patent offices in the United Kingdom, China, Japan, Australia, New Zealand, Mexico, and other countries, have issued patents for the use of CRISPR-Cas9 gene editing in all types of cells.

University of California has a long-standing commitment to develop and apply its patented technologies, including CRISPR-Cas9, for the betterment of humankind. Consistent with its open-licensing policies, UC allows nonprofit institutions, including academic institutions, to use the technology for non-commercial educational and research purposes.

In the case of CRISPR-Cas9, UC has also encouraged widespread commercialization of the technology through its exclusive license with Caribou Biosciences, Inc. of Berkeley, California. Caribou has sublicensed this patent family to numerous companies worldwide, including Intellia Therapeutics, Inc. for certain human therapeutic applications. Additionally, Dr. Charpentier has licensed the technology to CRISPR Therapeutics AG and ERS Genomics Limited.

On September 10, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported the presentation of updated phase 1 data for U3-1402, an investigational HER3 targeting antibody drug conjugate (ADC), in 30 patients with metastatic EGFR mutated, TKI resistant non-small cell lung cancer (NSCLC) (Press release, Daiichi Sankyo, SEP 10, 2019, https://www.prnewswire.com/news-releases/updated-phase-1-data-for-daiichi-sankyos-u3-1402-in-patients-with-egfr-mutated-nsclc-presented-at-2019-world-conference-on-lung-cancer-300914515.html [SID1234539384]). The late-breaking data were featured today in a Mini Oral Session at the IASLC 2019 World Conference on Lung Cancer (#WCLC19) in Barcelona, Spain (#MA21.06, Abstract #1720).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Updated efficacy results for 26 patients who received U3-1402 in one of four dose cohorts, and had baseline and at least one post-baseline tumor assessment, showed six confirmed partial responses across three dose levels. A reduction in tumor size was observed in 22 patients across all doses, with median best percentage change of -25.7 percent [range -82.6 percent to 13.3 percent]. Responses were reported in patients with and without a history of CNS metastases. All 30 patients in the trial had received prior treatment with an EGFR tyrosine kinase inhibitor (TKI) including 28 (93 percent) with osimertinib. Fifteen patients (50 percent) had also received prior chemotherapy. The median follow-up time was 4.5 months. At the time of data cut-off on May 3, 2019, a total of 17 patients remained on treatment.

Next-generation sequencing (NGS) and cfDNA analysis determined the presence of multiple resistance mechanisms to prior EGFR TKI therapies in patients who experienced partial responses and tumor reduction while being treated with U3-1402. Three patients with confirmed partial response harbored the EGFR resistance mutations T790M, which is the target of osimertinib, and C797S, which is associated with resistance to osimertinib. Additionally, all evaluable tumors demonstrated HER3 expression at various levels in retrospective immunohistochemistry (IHC) analysis (n=25).

"As more patients are treated on study, the findings continue to demonstrate activity with U3-1402, including ongoing confirmed partial responses, in patients with EGFR-mutant metastatic non-small cell lung cancer that is no longer responding to EGFR TKI therapy," said Helena Yu, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, and a trial investigator. "These data suggest that targeting HER3 with U3-1402 may be an effective treatment strategy irrespective of mechanism of resistance identified in the setting of EGFR TKI resistance, where new precision treatments are needed."

Preliminary safety data for 30 patients who received U3-1402 in one of four doses indicated a manageable safety profile for U3-1402 at a median treatment exposure of 3.2 months. The recommended dose for expansion has been established at 5.6 mg/kg. The most common treatment-emergent adverse events (TEAEs) of any grade, occurring in ≥30 percent of patients, included nausea (63.3 percent), fatigue (43.3 percent), vomiting (36.7 percent) and platelet count decrease (30 percent). One TEAE grade ≥3 occurred in more than 10 percent of patients (platelet count decrease, 20 percent). The following dose-limiting toxicities were observed in four patients: four grade 4 platelet count decrease and one grade 3 febrile neutropenia. One patient experienced a TEAE associated with treatment discontinuation (3.3 percent). Nine patients (30 percent) experienced treatment-emergent serious adverse events regardless of causality. Four patients (13.3 percent) experienced treatment-emergent serious adverse events that were drug-related.

"HER3 is frequently overexpressed in non-small cell lung cancers as well as other types of solid tumors, but no HER3 targeting therapies are approved for NSCLC or any cancer," said Dalila Sellami, MD, Vice President, U3-1402 Global Team Leader, Global Oncology Research and Development, Daiichi Sankyo. "U3-1402 is a potential first-in-class ADC designed to target and deliver treatment directly to HER3 expressing tumors, and based on these results, we will advance to dose expansion and broaden the scope of the trial to include patients with squamous or non-squamous NSCLC."

About the Study
The global, phase 1, open label, two-part study is enrolling patients with metastatic or unresectable EGFR mutated NSCLC whose disease has progressed while taking an EGFR TKI. The first part of the study includes patients who either experienced disease progression on erlotinib, gefitinib, dacomitinib or afatinib and tested negative for the T790M mutation or who experienced disease progression on osimertinib regardless of T790M status. The primary objectives of the study are to assess the safety and tolerability of U3-1402. Secondary study objectives are to evaluate preliminary efficacy by measuring antitumor activity of U3-1402 and to characterize the pharmacokinetics of U3-1402. Part one (dose escalation) assesses U3-1402 at four doses (3.2 mg/kg to 6.4 mg/kg) to determine a recommended dose for expansion. Part two (dose expansion) will evaluate U3-1402 at the recommended dose for expansion of 5.6 mg/kg and include an additional cohort of patients with metastatic squamous or non-squamous NSCLC without EGFR mutation whose disease has progressed after chemotherapy and anti-PD-L1 regimens. The study is expected to enroll more than 100 patients at approximately 17 sites globally. For more information, visit ClinicalTrials.gov.

About U3-1402
Part of the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise, U3-1402 is an investigational and potential first-in-class HER3 targeting ADC. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, U3-1402 is comprised of a human anti-HER3 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

U3-1402 is one of three Daiichi Sankyo ADCs in clinical development for NSCLC in addition to DS-1062 and [fam-] trastuzumab deruxtecan (DS-8201), which is being co-developed and co-commercialized globally in collaboration with AstraZeneca. U3-1402 is also being evaluated in a phase 1/2 study in patients with HER3 positive metastatic breast cancer.

U3-1402, DS-1062 and DS-8201 are investigational agents that have not been approved for any indication in any country. Safety and efficacy have not been established.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide; there were an estimated 2.1 million new cases of lung cancer in 2018 and 1.8 million deaths.1 Most lung cancers are diagnosed at an advanced or metastatic stage.2 Non-small cell lung cancer (NSCLC) accounts for 80 to 85 percent of all lung cancers.3 The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, for those who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.4

EGFR mutation is a well-established oncogenic target for management of advanced stage NSCLC.5 For patients with advanced EGFR mutated NSCLC, targeted therapy with EGFR TKIs offers higher response rates and progression-free survival compared to chemotherapy.5 However, most patients eventually develop resistance to the drugs, at which point treatment options become more limited.6 Clinical resistance to EGFR TKIs has been linked to multiple gene-based mechanisms, and in many cases, the underlying cause remains unknown.7,8,9 At the same time, a majority of EGFR mutant NSCLCs show some level of HER3 expression.10,11

HER3 is a member of the human epidermal growth factor receptor (EGFR) family of tyrosine kinase receptors, which are associated with aberrant cell growth.12 HER3 expression has been associated with increased metastases and reduced survival in patients with non-small cell lung cancer, where frequency has been reported as high as 75 percent.13 HER3 is overexpressed in several types of cancers.14 In recent years, researchers have recognized potential for HER3 as a therapeutic target.12 Currently, no HER3 targeting agents are approved for NSCLC or any cancer.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On September 10, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported the presentation of updated phase 1 clinical results and new biomarker data for DS-1062, an investigational TROP2 targeting antibody drug conjugate (ADC), in 52 unselected patients with heavily pretreated advanced non-small cell lung cancer (NSCLC). The data were featured today in a Mini Oral Session at the IASLC 2019 World Conference on Lung Cancer (#WCLC19) in Barcelona, Spain (#MA25.10, Abstract #3854) (Press release, Daiichi Sankyo, SEP 10, 2019, https://www.prnewswire.com/news-releases/updated-clinical-results-and-new-biomarker-analyses-presented-for-daiichi-sankyos-ds-1062-in-patients-with-advanced-nsclc-at-2019-world-conference-on-lung-cancer-300914513.html [SID1234539383]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Updated efficacy results for 46 evaluable patients who received DS-1062 at one of eight doses (0.27 mg/kg to 10.0 mg/kg) showed 12 partial responses (10 confirmed, 2 early) observed in a dose-dependent manner. Five of the confirmed partial responses were observed among seven patients (71.4 percent) receiving DS-1062 at 8 mg/kg, the recommended dose for expansion. The other two patients receiving the 8 mg/kg dose experienced stable disease, and six of the seven are continuing on trial. Patients had received prior treatments, including immune checkpoint inhibitors (86.5 percent), EGFR inhibitors and ALK inhibitors. The data cut-off was July 3, 2019. Thirty-five patients were ongoing in the trial as of August 20, 2019.

Thirty-five patients were evaluable for TROP2 expression by immunohistochemistry (IHC) analysis. TROP2 expression trended higher in patients who experienced a partial response. Gene analysis suggested SLFN11 expression, which has previously been associated with response to topoisomerase I inhibitors, trended higher in patients with tumor reduction.1 In addition, data showed a decrease in cfDNA in patients who experienced partial response and stable disease.

"There is a need for new treatment options to help patients with advanced non-small cell lung cancer that continues to progress on standard therapies, and these findings with DS-1062 in heavily pretreated patients are encouraging," said Rebecca S. Heist, MD, MPH, Medical Oncologist, Massachusetts General Hospital, Cancer Center, and a study investigator. "Further study in more patients at the recommended expansion dose will help further assess the potential for targeting TROP2 with DS-1062 in NSCLC."

Updated data for 52 patients evaluable for safety as of July 3, 2019 showed that DS-1062 was well-tolerated in doses up to 8 mg/kg, which is defined as the maximum tolerated dose and the recommended dose for expansion. The most common treatment-emergent adverse events (any grade, occurring in ≥ 30 percent of patients) included fatigue (36.5 percent) and nausea (36.5 percent). Twenty-two patients (42.3 percent) experienced at least one treatment emergent adverse event (TEAE) ≥ grade 3. Dose-limiting toxicities occurred in two patients at the 10 mg/kg dose (one mucosal inflammation and one stomatitis) and in one patient at the 6 mg/kg dose (rash maculopapular). TEAEs led to discontinuation in two patients (3.8 percent). Serious TEAEs were reported in 14 patients (26.9 percent) regardless of causality. One patient (1.9 percent) with disease progression treated with the 6.0 mg/kg dose developed an adverse event of special interest (respiratory failure, grade 5). Any pulmonary events suspected of being interstitial lung disease (ILD) or pneumonitis are considered adverse events of special interest and evaluated by an independent adjudication committee. The case was adjudicated and determined not to be ILD. Since the data cutoff, four potential cases of ILD have been reported and are pending adjudication: one grade 2 pneumonitis [6.0 mg/kg], one grade 2 organizing pneumonia [8.0 mg/kg], one grade 2 pneumonitis [8.0 mg/kg] and one grade 5 respiratory failure in a patient with disease progression [8.0 mg/kg].

"These findings support DS-1062 as a potential TROP2 targeting therapy for NSCLC and further reinforce the strength and flexibility of our DXd ADC platform, which enables each of our ADCs to be custom designed to potentially provide an optimal balance of safety and efficacy," said Eric Slosberg, PhD, Head, Global Translational Development, Oncology Research and Development, Daiichi Sankyo. "As the study advances, we will continue with our translational research to help uncover underlying factors contributing to patient response and identify patients most likely to respond to DS-1062."

DS-1062 was designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver chemotherapy inside cancer cells that express TROP2 as a cell surface antigen. The DXd ADC technology provides flexibility to adapt the drug-to-antibody ratio (DAR) or the number of DXd molecules conjugated per antibody. DS-1062 has a DAR of four, which is based on initial preclinical research into the construct necessary for intended safety and efficacy in TROP2 expressing tumors. Preclinical studies have demonstrated that DS-1062 selectively binds to the TROP2 receptor on the surface of a tumor cell. It is proposed that DS-1062 is then brought inside the cancer cell where lysosomal enzymes break down the tetrapeptide-based linker and release the DXd payload.

About the Phase 1 Study
The phase 1, first-in-human open-label study is investigating the safety and tolerability of DS-1062 in patients with unresectable advanced NSCLC who are refractory to or have relapsed following standard treatment or for whom no standard treatment is available. The first part of the study (dose escalation) assesses the safety and tolerability of increasing doses of DS-1062 to determine the maximum tolerated dose and recommended dose for expansion. The second part of the study (dose expansion) will evaluate the safety and tolerability of DS-1062 at the recommended dose for expansion and will enroll 40 additional patients with advanced NSCLC. Study endpoints include safety, pharmacokinetics, objective response rate, duration of response, disease control rate, time to response, progression-free survival, overall survival, biomarker analysis and immunogenicity. The study is currently enrolling patients with unresectable advanced NSCLC in the United States and Japan. For more information about the study, visit ClinicalTrials.gov.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide; there were an estimated 2.1 million new cases of lung cancer in 2018 and 1.8 million deaths.2 Most lung cancers are diagnosed at an advanced or metastatic stage.3 Non-small cell lung cancer (NSCLC) accounts for 80 to 85 percent of all lung cancers.4 The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, for those who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.5

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is highly expressed on several types of solid tumors, including NSCLC.6,7 Researchers have recognized TROP2 as a promising molecular target for therapeutic development in various types of malignancies, including NSCLC.7,8 Overexpression of TROP2 has been associated with increased tumor aggressiveness and decreased survival in several cancers.9 High TROP2 expression was identified in 64 percent of non-small cell adenocarcinomas and 75 percent of non-small cell squamous cell carcinomas in one study.6 Currently, no TROP2 targeting therapy is approved for NSCLC or any cancer.

About DS-1062
Part of the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise, DS-1062 is an investigational TROP2 targeting ADC. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-1062 is comprised of a humanized anti-TROP2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-1062 is one of three Daiichi Sankyo ADCs in clinical development for NSCLC in addition to U3-1402 and [fam-] trastuzumab deruxtecan (DS-8201), which is being co-developed and co-commercialized globally in collaboration with AstraZeneca.

DS-1062, U3-1402 and DS-8201 are investigational agents that have not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On September 10, 2019 Novigenix SA, a leading Immuno-Transcriptomics company that develops and commercializes solutions for early cancer detection and precision medicine, reported the discovery of a new molecular signature in blood that can be used for early colorectal cancer detection using its new LITOseek platform (Press release, Novigenix, SEP 10, 2019, View Source [SID1234539382]). Data explaining the use of next generation sequencing (NGS) and machine learning from the studies leading to this discovery will be presented at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting (27th September -1st October, Barcelona, Spain).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company’s currently marketed test, Colox, is the first commercially available Immuno-Transcriptomic blood based RT-PCR test on the market for the screening of colon cancer. The data regarding the discovery and development of a new Immuno-Transcriptomic molecular signature test for early colon cancer screening on the LITOseek platform will be presented at ESMO (Free ESMO Whitepaper).

The data will be presented on September 30, 2019 by our academic partner from The Swiss Institute of Bioinformatics under the title "Discovery of an Immuno-Transcriptomics signature in blood for early colorectal cancer detection" in the Poster Display Session 3 on Biomarkers.

Novigenix has also launched its re-designed website, which reflects the Company’s new business strategy and provides details on the LITOseek technology platform.

"Our new website and branding for the LITOseek technology platform illustrates Novigenix’s aspiration to become a market leader in data-driven medicine and will help our stakeholders to better understand the value proposition of our oncology business," said Dr. Jan Groen, CEO of Novigenix. "Part of the new strategy is the move from RT-PCR to a full immuno-transcriptome sequencing technology. Through the newly developed LITOseek platform, we will be able provide our customers with an NGS-based solution allowing them to implement our proprietary data analysis pipeline on their own instruments. Currently Novigenix is the first liquid biopsy based immuno-transcriptomic NGS company in the molecular diagnostic arena."

Convergence in Oncology Summit

Dr. Jan Groen will lead the discussion of the panel "Advances in Molecular Diagnostics: Early Cancer Detection & Therapy Optimization" at the next Convergence in Oncology Summit. The panel starts at 13:15 on 12 September 2019 in Lausanne, Switzerland.

About LITOseek

Novigenix’s blood Immuno-Transcriptomic sequence platform, LITOseek, analyzes the gene expression modifications (mRNA signatures) induced by the host response to various triggers, such as the onset of cancer. Disease specific algorithms are developed combining the mRNA signature with clinical and medical parameters. The combination of mathematical models with machine learning and collection of new data enables the continuous improvement of the predictive and adaptive algorithms.