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Taiho Pharmaceutical Obtains Approval of Anticancer Agent TAS-102 (brand name in Japan "Lonsurf®") in China for Treatment of Colorectal Cancer

On September 6, 2019 Taiho Pharmaceutical Co., Ltd. reported that the China National Medical Products Administration (NMPA) has approved the anticancer agent TAS-102 (brand name in Japan "LonsurfⓇ", trifluridine/tipiracil (FTD/TPI), development code TAS-102) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, in addition, might be treated or not able to be treated by an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy (Press release, Taiho, SEP 6, 2019, View Source [SID1234539338]).

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This approval is based on the results of the Phase III TERRA study on patients with refractory mCRC in Asia (China, South Korea, and Thailand). The study met the primary efficacy endpoint of statistically prolonging overall survival (OS) in patients with unresectable advanced or recurrent colorectal cancer. The drug appeared to be generally well tolerated and its toxicities were consistent with what has been previously reported.

With this latest approval, Taiho Pharmaceutical expects that Lonsurf will make a broader contribution to patients and medical institutions as a new treatment option for patients with colorectal cancer.

About the TERRA study
The TERRA study was a randomized, double-blind, placebo-controlled Phase III comparison study evaluating the efficacy and safety of orally administered TAS-102 in patients with refractory mCRC. The study enrolled 406 patients who received at least two prior regimens of standard chemotherapies for mCRC and were refractory or intolerant those chemotherapies. The study was conducted in China, South Korea, and Thailand. Patients were randomly assigned to receive either TAS-102 or placebo in order to investigate the efficacy of TAS-102. The primary objective of the TERRA study was improvement in OS versus placebo. The study was conducted under the leadership of principal researchers in China, South Korea, and Thailand. Results from TERRA study were presented at ESMO (Free ESMO Whitepaper) 2016 Congress and e-published in the Journal of Clinical Oncology in 2017*1.

About Colorectal Cancer
The number of patients with colorectal cancer in China is on the rise. It is the fifth most common cancer cause of death in China after lung cancer, gastric cancer, hepatic cancer, and esophageal cancer. It has been reported that around 250,000 people died of colorectal cancer in China in 2018.*2

About Lonsurf
Lonsurf is an oral anticancer drug, which utilizes the combination of trifluridine (FTD) and tipiracil (TPI), whose dual mechanism of action is designed to maintain clinical activity and differs from conventional fluoropyrimidines. FTD is an antineoplastic nucleoside analogue, which is incorporated directly into the DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

In Japan, Taiho Pharmaceutical has been marketing Lonsurf for the treatment of unresectable advanced or recurrent colorectal cancer since 2014. Since receiving FDA approval in 2015, Taiho Oncology, Inc., a U.S. subsidiary of Taiho Pharmaceutical, has been marketing Lonsurf in the United States for mCRC refractory to prior therapy.

Taiho Pharmaceutical and Servier*2 have an exclusive license agreement for the co-development and commercialization of Lonsurf in Europe and other countries outside of the United States, Canada, Mexico, and Asia. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TTY Biopharm launched Lonsurf in Taiwan in 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of August 2019, Lonsurf has been approved as a treatment for advanced mCRC in 72 countries and regions worldwide. Lonsurf has been approved as a treatment for metastatic gastric cancer in the United States in February 2019, in Japan in August 2019 and in EU in September 2019.

*1 Xu, J., Kim T., Shen L., et al. Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study, Journal of Clinical Oncology, 2018; 36(4): 350-358.

*2 WHO International Agency for Research on Cancer. CANCER TODAY. Colorectal cancer: Estimated number of deaths in 2018, China, both sexes, all age

View Source;mode=cancer&mode_population=who&population=900&populations=160&key=asr&sex=0&cancer=39&type=1&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=5&group_cancer=1&include_nmsc=1&include_nmsc_other=1#collapse-group-0-3

(Accessed August 22, 2019)

*3 Servier is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes).

European Commission approves Roche’s Tecentriq in combination with chemotherapy for the initial treatment of people with extensive-stage small cell lung cancer

On September 6, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved and granted marketing authorisation for Tecentriq (atezolizumab) in combination with chemotherapy (carboplatin and etoposide) for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Hoffmann-La Roche, SEP 6, 2019, View Source [SID1234539337]).

"This approval makes Tecentriq the first cancer immunotherapy available in Europe for the initial treatment of extensive-stage small cell lung cancer, marking an important step forward for patients," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The combination of Tecentriq and chemotherapy has been shown to improve survival compared to the current standard-of-care – an advance that, until now, has been difficult to achieve due to the refractory nature of this disease."

This approval is based on results from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared with chemotherapy alone (median overall survival [OS]=12.3 versus 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54–0.91; p=0.0069) in the intention-to-treat (ITT) population. The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival [PFS]) compared with chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95% CI, 0.62–0.96; p=0.017).1 Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.

Lung cancer is the leading cause of cancer death worldwide2 and SCLC accounts for approximately 15% of all lung cancer cases, with the majority of patients (70%) diagnosed in the "extensive stage", often meaning a poor prognosis.3 SCLC is distinguished from other lung cancer subtypes due to its aggressive nature, rapid growth, and early development of metastatic disease.3

Currently, Roche has nine Phase III lung cancer studies underway evaluating Tecentriq alone or in combination with other medicines across different types of lung cancer. Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across lung, genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) versus chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve adults with ES-SCLC. The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were PFS, as determined by the investigator using RECIST v1.1, and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below:1

Tecentriq in combination with chemotherapy helped people live significantly longer, compared with chemotherapy alone (OS=12.3 versus 10.3 months; HR=0.70, 95% CI: 0.54-0.91, p=0.0069) in the ITT population.
The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared with chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95% CI: 0.62–0.96, p=0.017).
Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.
Grade 3–4 treatment-related adverse events occurred in 56.6% of people receiving Tecentriq plus chemotherapy, compared with 56.1% of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving Tecentriq plus chemotherapy were low white blood cell count (neutropenia; 23%), anaemia (14%), decreased neutrophil count (14%) and thrombocytopenia (10%).
About SCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.3

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is 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 is a cancer immunotherapy (CIT) that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive triple-negative breast cancer.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

European Commission approves Roche’s new Tecentriq-based combination therapy as an initial treatment for most common form of advanced lung cancer

On September 6, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved and granted marketing authorisation for Tecentriq (atezolizumab) in combination with chemotherapy (carboplatin and Abraxane [albumin-bound paclitaxel; nab-paclitaxel]), for the initial (first-line) treatment of adults with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR mutant or ALK-positive NSCLC (Press release, Hoffmann-La Roche, SEP 6, 2019, View Source [SID1234539336]).

"Today’s approval marks another advance for people living with non-squamous non-small cell lung cancer, providing a new treatment option for those affected in Europe," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This Tecentriq-based combination expands treatment options and offers flexibility to physicians when making treatment choices combining immunotherapy with chemotherapy – which is important, given the complexity of lung cancer."

This approval is based on results from the Phase III IMpower130 study, which demonstrated that the Tecentriq combination therapy helped people live significantly longer, compared with chemotherapy alone (median overall survival [OS]=18.6 versus 13.9 months; hazard ratio [HR]=0.79; 95% CI: 0.64–0.98; p=0.033) in the intention-to-treat wild-type (ITT-WT) population.1 The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival [PFS]) compared with chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001) in the ITT-WT population.1 The safety profile of the Tecentriq combination therapy was consistent with that observed in previous studies.

Lung cancer is the leading cause of cancer death globally, and each year 1.76 million people die as a result of the disease, which translates into more than 4,800 deaths worldwide every day.2 NSCLC is the most prevalent type of lung cancer, accounting for around 85% of all cases.3

About the IMpower130 study
IMpower130 is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 723 people who were randomised (2:1) to receive:

Tecentriq plus carboplatin and nab-paclitaxel (Arm A), or
Carboplatin and nab-paclitaxel (Arm B, control arm)
During the treatment-induction phase, people in Arm A received Tecentriq and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurred first. People received Tecentriq during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive Tecentriq as monotherapy until disease progression.

The co-primary endpoints were:

PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) in the ITT-WT population
OS in the ITT-WT population
A summary of the ITT-WT data from the IMpower130 study that support this approval is included below:1

Tecentriq in combination with chemotherapy helped people live significantly longer, compared with chemotherapy alone (median OS=18.6 versus 13.9 months; HR=0.79; 95% CI: 0.64–0.98; p=0.033).
Tecentriq in combination with chemotherapy significantly reduced the risk of disease worsening or death (PFS) by 36% compared with chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001).
Tecentriq in combination with chemotherapy shrank tumours (objective response rate [ORR]) in 49.2% of people (95% CI: 44.49–53.96) compared with 31.9% of people (95% CI: 25.84–38.36) on chemotherapy alone.
The median duration of response (DoR) for people receiving Tecentriq in combination with chemotherapy was 8.4 months (95%, CI: 6.9–11.8) compared with 6.1 months (95% CI: 5.5–7.9) for people on chemotherapy alone.
Grade 3–4 treatment-related adverse events (AEs) were reported in 73.2% of people receiving Tecentriq plus chemotherapy compared with 60.3% of people receiving chemotherapy alone. The most common Grade 3–4 AEs in people receiving Tecentriq plus chemotherapy were an abnormal low count of a certain type of white blood cell (neutropenia, 32.1%), a decrease in red blood cells (anaemia, 29.2%), and a decreased neutrophil count (12.1%).
About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.3 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.3

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

Novartis investigational lung cancer therapy capmatinib (INC280) granted FDA Breakthrough Therapy Designation for patients with MET-mutated advanced non-small cell lung cancer

On September 6, 2019 Novartis reported that the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to capmatinib (INC280) as a first-line treatment for patients with metastatic MET exon14 skipping-mutated non-small cell lung cancer (NSCLC)," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis.

Recent research concludes that the cMET gene is an oncogenic driver[1],[2], and the investigational lung cancer therapy capmatinib has been shown to be a highly potent and selective MET inhibitor. The MET mutation is seen in an estimated 3% – 4% of all patients with NSCLC[3]. These patients are generally older and often have a poor prognosis that can limit lung cancer treatment options[4-6]. "As we continue to reimagine medicine and place a renewed focus on the development of innovative lung cancer treatments, we look forward to working with the FDA and global health authorities to bring capmatinib to patients who currently have no available targeted therapy options," continued Dr. Tsai.

According to FDA guidelines, treatments that receive Breakthrough Therapy Designation must target a serious or life-threatening disease and demonstrate a substantial improvement over existing therapies on one or more significant preliminary research endpoints. The FDA granted Breakthrough Therapy Designation for capmatinib based on positive primary results from the GEOMETRY mono-1 study presented at the 2019 meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). Please click link for complete study results [http://bit.ly/2L7L3ta]

Capmatinib (INC280) is an investigational, oral, highly potent and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Selvita Announces First Patient Dosed in Phase 1b Study of CDK8 Inhibitor SEL120 in the Treatment of Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

On September 6, 2019 Selvita (WSE: SLV) reported that the first patient enrolled in the Phase 1b study of company’s selective CDK8 inhibitor, SEL120, has received the first dose. SEL120 is being initially investigated in the treatment of patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) (Press release, Selvita, SEP 6, 2019, View Source [SID1234539321]). This open-label, dose-escalation study is being conducted at multiple sites in the U.S. and evaluates the safety, tolerability and the preliminary activity of SEL120, as well as establishing a recommended dose for further clinical development.

"CDK8 represents an important potential therapeutic target in cancer. SEL120, an orally available small molecule, is potentially the best in class CDK8 inhibitor and is the first in class to enter the clinical trials," commented Dr. Setareh Shamsili, Chief Medical Officer of Selvita.

"SEL120 has been identified through our in-house discovery platform with having differentiating characteristics, such as high selectivity, and has potential for development in a broad range of both hematological and solid malignancies. In preclinical studies, SEL120 has shown strong proof of concept for the treatment of AML, a disease where patients still face poor prognosis. We’re very grateful for the strategic support and advisory role that The Leukemia & Lymphoma Society (LLS) has played in bringing SEL120 into clinical development through its Therapy Acceleration Program (TAP). We expect to share the preliminary results of SEL120 study with the oncology community in 2020."

This Phase 1b study is a multicenter, sequential, modified 3+3 dose escalation study in adult patients with AML or HR-MDS who are refractory to treatment or have relapsed after previous therapies. Patients will be enrolled in the study independent of specific tumor mutational burden. The study will also assess pharmacokinetic and pharmacodynamic parameters of SEL120. Selvita is the sole sponsor of the Study.

About SEL120

SEL120 is an oral, selective inhibitor of CDK8, a kinase which is a part of the mediator complex and is essential for the activity of super-enhancers important to the regulation of RNA transcription. CDK8 kinase is implicated in the development of hematological malignancies and solid tumors. SEL120 was discovered with the Selvita discovery engine platform and is currently in clinical development for the treatment of acute myeloid leukemia and high risk myelodysplastic syndrome. SEL120 has received support from The Leukemia & Lymphoma Society Therapy Acceleration Program (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers. More information about TAP program is available at: View Source