On December 11, 2019 Eli Lilly and Company (NYSE: LLY) reported the opening of the LIBRETTO-431 clinical trial [NCT04194944] for selpercatinib, also known as LOXO-292, for treatment-naïve RET fusion-positive non-small cell lung cancer (NSCLC) patients (Press release, Eli Lilly, DEC 11, 2019, View Source [SID1234552245]). Enrolled trial participants will be randomized to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab as initial treatment of their advanced or metastatic RET fusion-positive NSCLC.

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!

"Given the remarkable results of the LIBRETTO-001 trial, I am excited to open this important Phase 3 trial of selpercatinib, a highly selective and potent molecule that has previously demonstrated sustained responses with a well-tolerated safety profile," said Professor Ben Solomon, principal investigator at the Peter MacCallum Cancer Centre in Melbourne Australia. "This trial endeavors to generate outcome data that place patients with RET fusions alongside those with EGFR mutations and ALK fusions, as driver-positive populations that should be treated with targeted therapies in the first-line setting, rather than chemoimmunotherapy."

"This is an important milestone in the journey to further demonstrate the benefit of selpercatinib and the potential for people living with advanced or metastatic RET fusion-positive non-small cell lung cancer in the first-line setting against the current standard of care," said Anne White, president of Lilly Oncology. "Launching a trial of this size underscores the importance of now including RET fusions in the paradigm of genomic testing in lung cancer."

Trial Background
LIBRETTO-431 is a randomized Phase 3 clinical trial of patients with treatment-naïve RET fusion-positive NSCLC. The trial will enroll 400 patients with advanced or metastatic RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease. Enrolled trial participants will be randomized 1:1 to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab as initial treatment of their advanced or metastatic RET fusion-positive NSCLC. RET fusions may be identified using local testing. This trial’s primary endpoint is progression-free survival (PFS) and secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR), and intracranial ORR. For patients randomized to the control arm, crossover is allowed at progression.

About Selpercatinib (LOXO-292)
Selpercatinib, also known as LOXO-292, is a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. Selpercatinib was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms.

Selpercatinib has received breakthrough designations in RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancers.

About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2 percent of non-small cell lung cancer, 10-20 percent of papillary and other thyroid cancers and a subset of other cancers. Activating RET point mutations account for approximately 60 percent of MTC. RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET.

On December 11, 2019 Novigenix SA, a leading Immuno-Transcriptomics company that develops and commercializes solutions for early cancer detection and precision medicine, reported the development of a new immune cell type specific Immuno-Transcriptomic signature for the detection of colorectal cancer (CRC) in blood (Press release, Novigenix, DEC 11, 2019, View Source [SID1234552267]). The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress (11-14 December, Geneva, Switzerland).

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!

Immune cells play a key role in cancer progression. Their response to the tumor can promote or prevent tumor growth and can be used to increase the diagnostic power of a cancer detection test. In this study, RNA signatures specific for different immune cell types (neutrophils, monocyte, T cells, CD4, CD8, B cells, NK cells) were compiled from published data and tested on the RNA-seq transcriptome profiles of 561 peripheral blood mononuclear cells (PBMC) samples from 218 healthy donors, 189 CRC, 115 advanced adenomas and 39 other cancers patients. The signature analysis was performed on Novigenix’s LITOseek sequencing platform.

Myeloid cell (monocyte and neutrophil) RNA signatures were strongly upregulated in CRC compared to control samples (p<0.01), whereas the T-cell signature was significantly downregulated (p<0.01). The specificity of the different RNA signatures was demonstrated by their correlation with the respective cell count, performed with traditional method.

"These are very encouraging data on the utility of immune cell type specific RNA signature as biomarkers for CRC detection in blood," said Prof. Dr. G. Dorta from the Department of Gastroenterology and Hepatology at CHUV in Lausanne, Switzerland. "The correlation of the cell type specific RNA signature with traditional cell counting as well as the CRC discriminant power could be very valuable for the development of an early CRC detection test."

"This newly developed cell type specific RNA signature demonstrated strong differentiation power between CRC and other cancers," said Dr. Jan Groen, CEO of Novigenix. "Therefore, we are evaluating how a combination of cell type specific RNA signatures with a CRC specific profile could be incorporated into a test for the early diagnosis of colon cancer."

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.

On December 11, 2019 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported the appointment of Shehnaaz Suliman, M.D., MBA, M.Phil., as the company’s president and chief operating officer (Press release, Alector, DEC 11, 2019, View Source [SID1234552251]). In this new role, Dr. Suliman will oversee Alector’s day-to-day operations, including preclinical development, program management, and strategic and administrative functions. Dr. Suliman will report to Arnon Rosenthal, Ph.D., chief executive officer of Alector.

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!

"Shehnaaz’s background and expertise in drug development, strategy, portfolio management, and operational leadership uniquely position her to bring greater integration to our operations. Her strong track record of building and leading teams that can support the development of life-changing medicines comes at a key inflection point for Alector as we prepare to launch our first registrational trial in 2020," said Dr. Rosenthal. "Shehnaaz’s core leadership strengths will be invaluable to our entire organization, and we look forward to leveraging her insights as a thought partner and leader at Alector."

"Neurodegeneration affects millions of patients and families worldwide, and I am proud to be supporting Alector’s mission to find a cure for these diseases. As the leader in immuno-neurology, Alector has made substantial progress in rapidly advancing a broad clinical portfolio of novel and innovative programs," said Dr. Suliman. "As we advance our lead programs into late-stage clinical development and continue to progress our research pipeline, I look forward to partnering with the team to further our vision for finding cures for neurodegenerative diseases. I am excited to be joining the company at this important time and look forward to helping Alector execute our objectives and scale our organization effectively."

Dr. Suliman brings over 20 years of business development, drug development, strategic and operational expertise, and executive leadership skills to Alector. She joins Alector from Theravance Biopharma, where she served as senior vice president, corporate development and strategy, a position she held from July 2017 to March 2019. Prior to Theravance, Dr. Suliman worked for Genentech as a group leader and project team leader in the R&D Portfolio Management and Operations Group from September 2010 to May 2015 where she led and oversaw a number of neuroscience development programs. She was also vice president and global therapeutic head, Roche Partnering from June 2015 to July 2017. Dr. Suliman held various management roles of increasing responsibility at Gilead Sciences between January 2005 and September 2010. Before Gilead, Dr. Suliman was an investment banker with Lehman Brothers and Petkevich & Partners, advising public and private companies on buy- and sell-side transactions. She is a member of the board of directors of Ultragenyx Pharmaceutical, a biopharmaceutical company, and 10X Genomics, a life science technology company. Dr. Suliman received her M.D. from the University of Cape Town Medical School, South Africa, and holds an MBA, with distinction, and M.Phil. in development studies from Oxford University, where she was a Rhodes Scholar.

On December 11, 2019 Phoenix Biotechnology, Inc. ("Phoenix" or the "Company" www.phoenixbiotechnology.com) reported that it has completed the private placement of 1,373,400 shares of common stock for gross proceeds of $4,120,200 (Press release, Phoenix Biotechnology, DEC 11, 2019, View Source [SID1234552268]).

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 gross proceeds of the offering are expected to be used for general corporate purposes including funding Phoenix’s continuing research at The University of Texas M.D. Anderson Cancer Center, University of Nebraska and University of L’Aquila (Italy); filing and prosecuting the Company’s U.S. and international patent portfolio; and paying general and administrative expenses.

Robert A. Newman, Ph.D., President and Chief Science Officer, said, "We are grateful to have received significant new resources for our continued research efforts. The ongoing research of our lead drug against glioblastoma appears to be very promising. In addition, we are proud of the research recently published of our drug’s efficacy against HTLV-1, a virus that affects millions of people with devastating declines in their quality of life. All of our work is aimed at providing hope for those afflicted with serious diseases for which there are few, if any, meaningful therapeutic options. The funds recently raised will assist us in continuing this important work."

The shares of common stock have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws. This news release does not constitute an offer to sell or the solicitation of an offer to buy any security and shall not constitute an offer, solicitation or sale in any jurisdiction in which it would be unlawful.

On December 11, 2019 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) reported positive detailed data from the global pivotal Phase II single-arm DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody drug conjugate (ADC) and potential new medicine, in patients with HER2-positive metastatic breast cancer who received two or more prior HER2-targeted regimens (Press release, AstraZeneca, DEC 11, 2019, View Source [SID1234552252]).

The primary endpoint of objective response rate (ORR), confirmed by independent central review, was 60.9% with trastuzumab deruxtecan monotherapy (5.4mg/kg). Patients had a median of six prior therapies for metastatic disease (2-27).

Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at one year. The results were consistent across subgroups of patients.

José Baselga, Executive Vice President, Oncology R&D, said: "The clinically meaningful and durable responses seen among these patients illustrate the potential of trastuzumab deruxtecan to establish a new standard of care. These results are impressive, as women with this advanced stage of breast cancer have already endured multiple prior therapies for HER2-positive metastatic breast cancer."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "The strength of the pivotal results and the consistency with previously reported trastuzumab deruxtecan data further underscore that this specifically engineered HER2-targeted antibody drug conjugate is delivering on its intent of enhancing efficacy for patients with HER2-positive metastatic breast cancer."

Ian E. Krop, a principal investigator of the DESTINY-Breast01 trial and Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, said: "These results are particularly striking as trastuzumab deruxtecan prompted a high level of durable tumour reduction among patients, the majority of whom had exhausted most if not all standard therapies for HER2-metastatic breast cancer. We are excited by these results and their potential to help patients with this advanced stage of breast cancer."

Summary of resultsi
Efficacy measure
Total evaluable (n=184) ii

ORR (%) (95% CI)
60.9 (53.4-68)
CR (%)
6.0
PR (%)
54.9
SD (%)
36.4
PD (%)
1.6
DCR (%) (95% CI)iii
97.3 (93.8-99.1)
CBR (%) (95% CI)iv
76.1 (69.3-82.1)
Median DoR (95% CI)
14.8 months (13.8-16.9)
Median PFS (95% CI)
16.4 months (12.7-NE)
Estimated OS at 12 months (%) (95% CI)
86 (80-91)
CI, confidence interval; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not estimable.
i As assessed by independent central review.
ii 5.4mg/kg.
iii DCR is (CR + PR + SD)
iv CBR is (CR + PR + SD for ≥6 months)

The data were included as part of the press programme at the 2019 San Antonio Breast Cancer Symposium and simultaneously published online in The New England Journal of Medicine.

Prior therapies included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormone therapies (48.9%) and other systemic therapies (99.5%). Median treatment duration for trastuzumab deruxtecan was 10 months (0.7-20.5) with a median duration of follow-up of 11.1 months (0.7-19.9). As of data cut-off on 1 August 2019, 42.9% of patients remained on treatment.

The safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Breast01 was consistent with that observed in the Phase I trial. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (20.7%), anaemia (8.7%), nausea (7.6%), decreased white cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%). Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%) and no Grade 4 events. Four deaths (2.2%) were determined to be due to ILD.

Regulatory submission of trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer was recently accepted with Priority Review by the US Food and Drug Administration. A regulatory submission has also been made to Japan’s Ministry of Health, Labour and Welfare.

About HER2-positive breast cancer
Approximately one in five breast cancers are HER2-positive.1,2 Despite recent improvements and approvals of new medicines, there remains significant unmet needs for patients with advanced HER2-positive metastatic breast cancer.3,4 This disease remains incurable with patients eventually progressing after currently available treatments.3,4

About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poor prognosis in breast cancer patients.5 To be considered HER2-positive, tumour cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.1 A finding of IHC 3+ and/or FISH amplification is considered positive.1

About DESTINY-Breast01
DESTINY-Breast01 is a pivotal Phase II, single-arm, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. Enrolment into DESTINY-Breast01 was completed in September 2018 with 184 patients at more than 100 sites globally.

About trastuzumab deruxtecan
Trastuzumab deruxtecan (DS-8201; fam-trastuzumab deruxtecan in the US only); is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca’s ADC scientific platform. 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.

A comprehensive development programme is underway in North America, Europe and Asia, including five pivotal trials in HER2-expressing metastatic breast and gastric cancers, including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

About the collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan as a potential new medicine worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

About 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 at least six new medicines to be 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. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – 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.

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!