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]).

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"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

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]).

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"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

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 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

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

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.

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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.

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.

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"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

On September 5, 2019 OncoCyte Corporation (NYSE American: OCX), a developer of novel tests for the early diagnosis and management of lung cancer, reported that it has entered into a definitive agreement to acquire Razor Genomics (Press release, Oncocyte, SEP 5, 2019, View Source [SID1234551117]). An initial closing at which OncoCyte will acquire shares of Razor preferred stock representing 25% of the outstanding equity of Razor, is expected to close by the end of September, subject to customary and other closing conditions. OncoCyte will have the option to acquire the balance of the outstanding shares of Razor common stock from Razor’s shareholders (the "Purchase Option").

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Razor’s CLIA-certified treatment stratification test (the "Razor test") has been rigorously validated to identify early-stage lung cancer patients who are at high-risk versus low-risk of death within five years following surgical resection. The Razor test enables the identification of lung cancer patients at high risk for recurrence and allows them to be treated at a time when their cancer can still be responsive to adjuvant chemotherapy. Importantly, the recent decision by Centers for Medicare and Medicaid Services Molecular Diagnostic Services Program ("CMS") to recommend coverage for the Razor test is a significant inflection point for OncoCyte and accelerates the path to becoming a commercial stage company.

"Notwithstanding recent advancements in treatment, lung cancer remains a leading cause of cancer death. Approximately 30% of patients with surgically removed early stage lung cancer recur and over half of those that recur die within five years of surgery," said Ron Andrews, Chief Executive Officer of OncoCyte. "The addition of the Razor treatment stratification test for patients diagnosed with early stage lung cancer is a perfect downstream complement to our proprietary DetermaVu liquid biopsy test that we are developing to help manage CT-identified lung nodules and thereby facilitate the early diagnosis of lung cancer. The Razor test enables us to address an adjacent critical decision point that physicians and patients face during the lung cancer treatment journey that today remains unmet. There are many such decision points along this care continuum, and this transaction is a significant step forward for OncoCyte as we work to build a comprehensive diagnostic content company serving the needs of lung cancer patients across disease stages, from early diagnosis all the way through recurrence monitoring and beyond."

"Importantly, the Razor test is extensively validated and has been published in prestigious medical journals such as Lancet and the Journal of the American Medical Association. CMS’s recent proposed positive coverage decision to provide reimbursement reflects the clinical utility of the test and, we believe, will drive broad test adoption. There remain many significant unmet needs in the detection and treatment of lung cancer, and we are poised to occupy a leading position in providing molecular tests that can improve outcomes for lung cancer patients," Mr. Andrews concluded.

In a published clinical utility study, the five-year disease-free survival rate was 92% for individuals identified as high risk by the Razor test and treated with chemotherapy, compared to 49% in untreated high-risk patients. Similarly, individuals identified as low risk by the Razor test had a 5-year disease free survival of 94% without the use of chemotherapy. In this study, the test demonstrated higher accuracy at discriminating between high and low risk patients than current National Comprehensive Cancer Network (NCCN) guideline criteria for risk assessment.

In another published survey of physicians who ordered the test, approximately one in three physicians changed their treatment decision based on the results of the Razor test.

"The current staging system for lung cancer is not adequate and misses high risk patients who could benefit from chemotherapy," noted Dr. David M. Jablons, Professor and Chief of General Thoracic Surgery at the University of California San Francisco Medical Center. "The Razor treatment stratification test has been shown to improve the identification of high-risk patients over conventional staging, and when given chemo, these high-risk patients had a profound improvement in survival. In fact, a new staging approach that incorporates the Razor test has now been published in Journal of Thoracic Oncology."

Principal Transaction Terms:

Upon closing, OncoCyte will make a cash payment of $10 million for an initial 25% equity interest in the form of Razor preferred stock. OncoCyte will pay an additional $1 million milestone resulting from the positive CMS coverage decision recently received.

In addition, the selling shareholders of Razor are eligible to receive an additional $10 million in cash and $5 million of OncoCyte common stock, or shares of common stock and cash in certain circumstances, for all remaining shares of Razor upon the achievement of certain clinical trial milestones. Upon achievement of a clinical trial milestone, Razor’s shareholders are eligible to receive up to $3 million of OncoCyte common stock, or shares of common stock and cash in certain circumstances, and upon the achievement of an additional CMS coverage milestone, Razor’s parent company is entitled to receive a $4 million cash payment from OncoCyte.

Razor will reserve $4 million of the initial $10 million payment from our purchase of the preferred stock for use in financing a supplemental clinical trial of the Razor test. OncoCyte has agreed to pay future clinical trial costs in excess of that $4 million reserve, subject to ceilings under a clinical trial budget.

Conference Call Information:

OncoCyte management will host a conference call and webcast today, September 5, at 10:00am ET. To access the call and webcast, please use the information below:

Dial in (US): 877-407-9716

Dial-in (International): 201-493-6779

Webcast: View Source