On September 6, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from its broad clinical development programme across different types of lung cancer will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC), taking place from 23–26 September in Toronto, Canada (Press release, Hoffmann-La Roche, SEP 6, 2018, View Source [SID1234529353]). 10 abstracts have been accepted, including three ‘late breakers’ and five oral presentations.

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!

"We look forward to presenting new data from our comprehensive lung cancer programme, including new immunotherapy and targeted treatment strategies across different types of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are particularly pleased to be sharing positive TECENTRIQ data in extensive-stage small cell lung cancer, which has seen limited progress in treatment over the last two decades, as well as new pivotal data for our investigational therapy entrectinib for the treatment of ROS1 fusion-positive lung cancer."

Key presentations
Progression-free survival (PFS) and overall survival (OS) data from the Phase III IMpower133 study of TECENTRIQ plus chemotherapy (carboplatin and etoposide) for the initial (first-line) treatment of people with extensive-stage small cell lung cancer (ES-SCLC) will be presented in the Presidential Symposium. These are the first positive survival data from a Phase III study with an immunotherapy-based combination in the initial treatment of ES-SCLC.

PFS and OS data will be presented from the Phase III IMpower132 study investigating TECENTRIQ plus pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) in the initial treatment of people with advanced non-squamous NSCLC. The IMpower132 and IMpower133 data will be featured as part of WCLC’s official press programme on Monday 24th and Tuesday 25th of September, respectively.

Additionally, results from a Phase Ib study investigating Tarceva plus TECENTRIQ in tyrosine kinase inhibitor (TKI)-naïve people with EGFR mutation-positive NSCLC will also be presented.

New pivotal results of entrectinib, an investigational oral, CNS-active treatment for people with locally advanced or metastatic ROS1 fusion-positive NSCLC, from a pooled analysis including the global Phase II STARTRK-2 basket study will be presented. These data have also been selected to be featured in the WCLC press programme on Monday 24th of September.

Follow Roche on Twitter via @Roche and keep up to date with WCLC 2018 congress news and updates by using the hashtag #WCLC2018.

For more information on Roche’s approach to cancer, visit Roche.com.

Overview of key presentations featuring Roche medicines at WCLC 2018

About NSCLC and SCLC
Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85% of all cases,2 with SCLC accounting for approximately 15% of all lung cancer cases.2 Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis.3 The five-year relative survival rate for people with stage I SCLC is approximately 31%, however, at stage IV, the five-year relative survival rate declines to approximately 2%.4

About TECENTRIQ
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

About ROS1 fusion-positive non-small cell lung cancer (NSCLC)
ROS1 is a tyrosine kinase, which play a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, ‘healthy’ cell signalling malfunctions, causing cells to grow and proliferate in an uncontrolled manner – this results in cancer.

ROS1 gene fusions account for 1-2% of NSCLC. Lung cancer is the leading cause of cancer-related death across the world. Each year, 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 NSCLC is the most prevalent type of lung cancer, accounting for around 85% of all cases.2 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 fusions.

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK fusions. Entrectinib is being investigated across a range of solid tumour types, including NSCLC, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumours (GIST) and cancers of unknown primary (CUP).

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.

On August 6, 2018 Aileron Therapeutics (NASDAQ: ALRN), the clinical-stage leader in the field of stapled peptide therapeutics for cancers and other diseases, reported that Manuel Aivado, MD, PhD, has been named President and Chief Executive Officer and elected to its Board of Directors (Press release, Aileron Therapeutics, SEPT 6, 2018, View Source;p=irol-newsArticle&ID=2366358 [SID1234529414]). Since 2012, Dr. Aivado has served as Aileron’s Senior Vice President and Chief Medical and Scientific Officer. He succeeds John P. Longenecker, PhD, who was appointed interim CEO on May 15, 2018.

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!

"We are very pleased to announce this well-deserved promotion for Dr. Aivado," said Aileron Chairman Jeff Bailey. "Manuel clearly best exemplifies the skill set and talent needed to lead the company through its next stage of development."

"I am very excited to take on this new responsibility at Aileron as we further expand the clinical development of our lead product candidate, ALRN-6924, into combination therapies. ALRN-6924 represents the proof-of-concept for Aileron’s stapled peptide technology, which I believe to be capable of producing additional novel drug candidates that address previously undruggable targets," said Dr. Aivado. "In the future, we plan to broaden the applicability of our technology and expand our external collaborations. I am pleased with the external recognition that ALRN-6924 and our stapled peptide technology have earned in the scientific community, and I look forward to additional collaborations translating this recognition into therapeutic and commercial success."

Dr. Aivado brings more than 20 years of scientific, medical, and executive leadership to this position. Most recently, Dr. Aivado led Aileron’s clinical testing of stapled peptides against intracellular targets and designed and implemented the ALRN-6924 first-in-human trial. ALRN-6924 was selected for the "Best of ASCO (Free ASCO Whitepaper) Meetings," which highlights the most cutting-edge science and education from the world’s premier oncology event. Prior to joining Aileron, Dr. Aivado served as Vice President of Clinical Development and Pharmacovigilance at Taiho Oncology, Inc. He previously served as a Senior Medical Director in clinical development at GlaxoSmithKline. In addition, Dr. Aivado was an Instructor in Medicine at Beth Israel Deaconess Medical Center/Harvard Medical School. Prior to his industry experience, Dr. Aivado practiced clinical medicine in Germany for nearly ten years, during which he was awarded the Dr. Mildred Scheel cancer research scholarship award in 2002. Dr. Aivado is a German board-certified physician in internal medicine, hematology and medical oncology. He received his MD and PhD degrees from the Medical School of the University of Dusseldorf, Germany.

About ALRN-6924
ALRN-6924 is a first-in-class product candidate designed to reactivate wild-type p53 tumor suppression by disrupting the interactions between p53 and its two primary suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, the Company believes there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

On September 6, 2018 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immunotherapies derived from its Immulytic platform, reported the U.S. Food and Drug Administration (FDA) has accepted the Company’s investigational new drug (IND) application for its lead product candidate, RP1, for patients with solid tumors (Press release, Replimune, SEP 6, 2018, View Source [SID1234529738]). The Company intends to open its ongoing Phase 1/2 clinical trial in the U.S. and begin enrolling patients in the fourth quarter of 2018. The clinical trial is currently ongoing in the U.K., as previously announced.

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!

In part one of the Phase 1/2 clinical trial, Replimune is assessing the safety and tolerability of RP1 administered alone in patients with advanced solid tumors. Following this dose escalation phase, further patients will receive RP1 in combination with nivolumab anti-PD1 therapy. In part two of the Phase 1/2 clinical trial, expected to initiate in the first half of 2019, Replimune intends to study the safety and efficacy of RP1 in combination with nivolumab in approximately 120 patients with metastatic melanoma, metastatic bladder cancer, microsatelite instability high cancers, and non-melanoma skin cancers. For each of the tumor types other than melanoma, patients will be naïve to immune checkpoint blockade, whereas in melanoma, patients both previously treated and previously untreated with immune checkpoint blockade will be enrolled. This clinical trial is a collaboration with Bristol Myers Squibb, which is providing nivolumab for use in the study.

RP1 is Replimune’s first Immulytic product candidate to enter the clinic and is based on a proprietary new strain of herpes simplex virus engineered to maximize tumor killing potency. This is intended to result in highly immunogenic cell death and robust activation of a systemic anti-tumor immune response.

About Oncolytic Immunotherapy
Oncolytic immunotherapy is an emerging class of cancer therapy which exploits the ability of viruses to selectively replicate in and kill tumors, while at the same time inducing a potent, patient-specific, anti-tumor immune response. Oncolytic viruses have the ability to induce a robust immune response against a patient’s particular complement of tumor antigens, including neo-antigens, in situ in the patient in an off-the-shelf format. While clinically active alone, oncolytic immunotherapy may have synergy with certain other treatments and, in particular, with immune checkpoint blockade therapies.

On September 5, 2018 SpringWorks Therapeutics, a clinical-stage rare disease and oncology company focused on sourcing and developing innovative treatments for underserved patient populations, reported that the company’s Board of Directors has appointed Saqib Islam as chief executive officer (Press release, SpringWorks Therapeutics, SEPT 5, 2018, View Source [SID1234529295]). Mr. Islam, who previously served as chief financial and chief business officer at SpringWorks Therapeutics, will also join the Board of Directors.

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!

"After a thorough and thoughtful search process, we are pleased to appoint Saqib as SpringWorks Therapeutics’ inaugural CEO and a member of our Board. Saqib has demonstrated exceptional leadership in building SpringWorks and brings to bear a broad set of skills and experiences that will enable our future success. With Saqib as CEO, we are extremely well positioned to execute on our multiple initiatives to deliver promising science to underserved patient populations," said Daniel S. Lynch, Executive Chairman of SpringWorks Therapeutics.

Mr. Islam has led SpringWorks Therapeutics’ key business operations and strategic corporate planning activities since the company’s launch in September 2017. He joined SpringWorks Therapeutics from Moderna Therapeutics, where he served as chief business officer and oversaw global strategic planning, corporate development and business development. Prior to Moderna, Mr. Islam served as executive vice president, chief strategy and portfolio officer at Alexion Pharmaceuticals. Mr. Islam has over 25 years of international business management experience and an extensive background in the healthcare banking sector, having held managing director positions in the investment banking divisions of Morgan Stanley and Credit Suisse Securities. He received a bachelor’s degree from McGill University and a J.D. from Columbia Law School, where he was a Harlan Fiske Stone Scholar.

"I joined SpringWorks Therapeutics because I saw a unique opportunity to build a company centered around the ambition of developing transformative medicines for severe diseases that do not currently have a cure, starting with our two lead development programs for patients with desmoid tumors and neurofibromatosis type 1, two rare and devastating tumors," said Mr. Islam. "I am honored to have the opportunity to lead SpringWorks and am very pleased to have assembled an experienced management team comprised of leaders who share our mission-driven approach to serving patients, each of whom will play a critical role in advancing and building upon the great work that has been done thus far."

Experienced Leadership Team

SpringWorks Therapeutics has built a team of highly talented executives with deep industry experience and a proven track record in their respective areas of expertise.

Jens Renstrup, M.D., MBA, Chief Medical Officer: Dr. Renstrup is responsible for developing and driving execution of the clinical development programs and oversees medical affairs. He has extensive experience building medical affairs organizations at pharmaceutical and biotech companies, shaping early- to late-stage development pipelines, and a proven track record accelerating time to market and new drug approvals. Prior to joining SpringWorks Therapeutics, Dr. Renstrup served as senior vice president and head of global medical affairs at Alexion Pharmaceuticals and vice president and head of global medical affairs at GSK Vaccines. Earlier in his career, Dr. Renstrup served in progressive leadership positions at Merck & Co, and he started his career at IPSEN Scandinavia A/S. Dr. Renstrup holds an M.D. and specialist medical degree in anesthesiology and intensive care medicine from the University of Copenhagen, as well as an MBA from the Copenhagen Business School.
Badreddin Edris, Ph.D., Chief Business Officer: Dr. Edris is responsible for corporate strategy, business development and capital formation for the company. His professional experience spans private and public equity investing, company formation and operations, corporate and business development, and strategic and product planning in the biotechnology industry. Prior to joining SpringWorks Therapeutics, Dr. Edris was an investment and operating professional on the private equity team at OrbiMed, where he was involved in deal sourcing, evaluation and execution, as well as post-investment strategic and operational support for biotechnology companies across a range of therapeutic areas and stages of development. Dr. Edris also co-founded and held operating roles at two OrbiMed portfolio companies, Silverback Therapeutics (where he was chief business officer) and Edgewise Therapeutics (where he was chief operating officer). Before OrbiMed, Dr. Edris was a management consultant at Bain & Company, where he collaborated with global pharmaceutical and biotechnology companies on a range of strategic and operational projects. Dr. Edris received his Ph.D. in genetics from Stanford University, where he was an NSF research fellow.
L. Mary Smith, Ph.D., Senior Vice President, Clinical Research and Development: Dr. Smith is responsible for designing and running the clinical development programs for SpringWorks Therapeutics. Prior to joining SpringWorks Therapeutics, Dr. Smith was the executive vice president of gene therapy at Bamboo Therapeutics, a wholly owned subsidiary of Pfizer, where she led several key gene transfer programs for rare genetic diseases. Prior to joining Bamboo, Dr. Smith was the vice president of product development at United Therapeutics, with responsibility for biological development in oncology, as well as regenerative medicine and virology. Dr. Smith holds a Ph.D. in microbiology/immunology from the University of New Hampshire and received her post-doctoral training at Emory University.
Michael Greco, J.D., General Counsel and Secretary: Mr. Greco is responsible for the company’s legal and compliance functions. He is an experienced legal executive who previously served as senior vice president of law and corporate secretary for Alexion Pharmaceuticals. He joined Alexion shortly prior to the launch of Alexion’s first and lead product and during his tenure assumed positions of increasing responsibility in the company’s legal department. In his most recent role, he was responsible for overseeing corporate governance initiatives, public reporting and securities compliance and corporate transactions. He was also responsible for managing the legal department’s corporate, R&D, business development and employment law legal teams. Prior to Alexion, Mr. Greco was a corporate attorney at Wiggin and Dana LLP and Bingham McCutchen LLP (now Morgan Lewis). Before law school, Mr. Greco served in the U.S. Army Corps of Engineers. Mr. Greco received a J.D. from Suffolk University Law School and a Bachelor of Science degree from the United States Military Academy, West Point.
Lisa Sinclair, Head of Program and Alliance Management: Ms. Sinclair is responsible for portfolio management and alliance development with the company’s biopharmaceutical partners, including the collaboration with Pfizer. Ms. Sinclair brings significant experience in driving the delivery of medicines from IND through approval in top-tier global biopharmaceutical companies and has a proven track record of accelerating medicines to key decision points in rare diseases. Prior to joining SpringWorks Therapeutics, she served as vice president of R&D strategy, portfolio and project management at Alexion Pharmaceuticals, where she led the development and execution of the five-year R&D strategic plan across multiple disease franchises and built portfolio and project management capabilities that supported pipeline speed, growth and value. Prior to Alexion, Ms. Sinclair was vice president of R&D portfolio and performance at AstraZeneca, where she was accountable for transforming global portfolio management across R&D and implemented R&D therapeutic area planning, portfolio prioritization, resource management, and performance metrics and analytics. Prior to AstraZeneca, she held various roles of increasing responsibility at Pfizer. Ms. Sinclair received a bachelor’s degree in business from the University of Vermont.
Kim Diamond, Head of Communications and Investor Relations: Ms. Diamond is responsible for the company’s internal and external communications strategy and investor relations. She has significant experience across the biopharmaceutical industry, including an established track record of launching rare disease therapies and broad therapeutic area expertise in oncology, hematology, nephrology, neurology and metabolic disorders. Prior to joining SpringWorks Therapeutics, Ms. Diamond served as executive director of corporate communications at Alexion Pharmaceuticals, where she was responsible for global external communications, including company reputation and branding, global product launches, and digital communications. Prior to Alexion, Ms. Diamond was director of corporate communications at OSI Pharmaceuticals, and she also held roles of increasing responsibility in the healthcare practice of Edelman earlier in her career. Ms. Diamond received a bachelor’s degree from Middlebury College.

On September 5, 2018 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Merck & Co., Inc., Kenilworth N.J., U.S.A., known as MSD outside of the United States and Canada, reported that the China National Medical Products Administration (NMPA) approved the kinase inhibitor LENVIMA (lenvatinib) as a single agent for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Eisai, SEPT 5, 2018, View Source [SID1234529337]). In China, the application of LENVIMA was submitted in October 2017, and was designated for Priority Review by the NMPA due to LENVIMA’s significant clinical benefit compared to existing treatments, leading to approval in approximately 10 months. This approval marks the first for LENVIMA in China, where the incidence of HCC is high,1 and the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years.1

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 approval was based on results from the REFLECT study (Study 304),2 an open-label, Phase 3 trial where LENVIMA demonstrated a treatment effect on overall survival (OS)*1 by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC. LENVIMA demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS)*2, time to progression (TTP)*3 and objective response rate (ORR)*4. In a subpopulation analysis of 288 patients in the study from the greater Chinese region (mainland China, Hong Kong and Taiwan), LENVIMA demonstrated efficacy based on non-inferiority of OS compared to sorafenib, with improvements also observed in PFS, TTP and ORR3. Approximately 80% of patients in the subpopulation were living with HCC resulting from chronic hepatitis B virus (HBV), which has high unmet medical need. For these patients, LENVIMA demonstrated non-inferiority based on OS compared with sorafenib, thereby demonstrating the effect of LENVIMA in patients with HCC resulting from HBV. (For the detailed data, please refer to "Notes for Editors" below.)

In the China package insert, the five most common adverse reactions observed in patients treated with LENVIMA were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%) and decreased weight (31%), which is consistent with the known side-effect profile of LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in Asian regions. Specifically, in China, there are approximately 395,000 new cases and 380,000 deaths per year, accounting for approximately 50% of cases worldwide.1 HCC accounts for 85% to 90% of primary liver cancer cases. Unresectable HCC, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.

Since the initial launch, more than 10,000 patients have been treated with LENVIMA. Today, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries including the United States, Japan, in Europe and Asia, and as combination with everolimus as a second-line treatment for renal cell carcinoma (RCC) in over 45 countries including the United States and in Europe. For HCC, LENVIMA was approved for use in Japan in March 2018, and in the United States and Europe in August 2018. In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since approval of this indication.

*1 Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.

*2 Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.

*3 Time To Progression: TTP is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression. Unlike PFS, TTP does not consider death from any cause.

*4 Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

About the REFLECT Trial (Study 304) 2

REFLECT was a large (n=954) Phase 3, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of LENVIMA versus sorafenib as a first-line systemic treatment in patients with unresectable HCC. Patients at 154 trial sites in 20 countries were randomized to receive LENVIMA 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was OS, tested first for non-inferiority to sorafenib, then for superiority. The key secondary efficacy endpoints of this study included PFS, TTP and ORR, tested for superiority to sorafenib.

In the China package insert, REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]: 0.79-1.06). Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS, TTP and ORR, as confirmed by a blinded independent imaging review:

• Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
• Median TTP was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
• LENVIMA showed nearly 3.5 times the ORR of sorafenib: 40.6% (95% CI: 36.2-45.0) versus 12.4% (95% CI: 9.4-15.4) per blinded independent imaging review based on mRECIST criteria (odds ratio 5.01, 95% CI: 3.59-7.01; p<0.00001).

About the Subpopulation Analysis of Patients from the Greater Chinese Region3

The results of subpopulation analysis of patients from the greater Chinese region3 were based on 288 patients out of the 954 HCC patients who participated in the REFLECT study. In this subpopulation analysis, median OS was 15.0 months for LENVIMA versus 10.2 months for sorafenib (HR: 0.73; 95% CI: 0.55-0.96; nominal p=0.02620). Independent imaging review based on mRECIST criteria revealed the following results: PFS (LENVIMA 8.4 months versus sorafenib 3.6 months in median [HR: 0.47; 95% CI: 0.35-0.64; nominal p<0.00001]), TTP (LENVIMA 9.2 months versus sorafenib 3.6 months in median [HR: 0.45; 95% CI: 0.33-0.62; nominal p<0.00001]) and ORR (LENVIMA 43.8% versus sorafenib 13.2% [odds ratio 5.14; 95% CI: 2.84-9.31; nominal p<0.00001]).

Additionally, of the 288 patients in the subpopulation, approximately 80% (n=242) were living with HCC resulting from HBV. An analysis of these patients revealed the following results for OS: LENVIMA (n=123) 14.9 months versus sorafenib (n=119) 9.9 months in median (HR: 0.72; 95% CI: 0.53-0.97).

About Unresectable Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year.2 There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. HCC accounts for 85% to 90% of primary liver cancer cases. HCC is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C HCC is on the rise. Surgery is the first option for treatment, but for patients with unresectable HCC who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (TACE), treatment options are limited and the prognosis is very poor.

About LENVIMA (lenvatinib mesylate)

Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for RCC in over 45 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for RCC.

In addition, LENVIMA has been approved as a treatment for hepatocellular carcinoma in Japan, the United States, Europe and South Korea. Eisai has submitted applications for an indication covering hepatocellular carcinoma in Taiwan (December 2017), as well as in other countries.

It is important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.