On May 29, 2020 Novartis reported updated results from the landmark COMBI-AD clinical trial, demonstrating that treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) following the surgical removal of melanoma offers a long-term and durable relapse-free survival (RFS) benefit to high-risk patients diagnosed with stage III, BRAF-mutation positive melanoma1 (Press release, Novartis, MAY 29, 2020, View Source [SID1234558667]). Researchers reported that 52% (95% CI, 48%-58%) of patients treated with adjuvant Tafinlar + Mekinist were alive and relapse-free at five years1. Among patients in the study’s placebo arm 36% (95% CI, 32%-41%) were alive and relapse-free at the time of this analysis, generally consistent with typical melanoma relapse-free survival rates seen among patients with resected stage III disease without treatment1,3-5. Consistent RFS benefit was observed across all AJCC 7 stage III subgroups1,6.

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Median RFS, or the length of time when 50% of patients are still alive and relapse-free, was not yet reached at the 5-year data cut-off for patients on Tafinlar + Mekinist treatment, suggesting long-term benefit of targeted therapy in the adjuvant (post-surgical) setting (NR; 95% CI, 47.9 mo-NR)1. Median RFS was 16.6 months for patients taking a placebo (95% CI, 12.7-22.1 mo)1. Treatment with Tafinlar + Mekinist reduced the risk of relapse or death by 49% compared to placebo (hazard ratio [HR] 0.51; 95% CI 0.42, 0.61)1.

"Our goal as clinicians is to give our stage III patients the best chance for relapse-free survival," said Prof. Axel Hauschild, MD, Professor of Dermatology, University Hospital Schleswig-Holstein, Germany. "Results from COMBI-AD show that adjuvant treatment with Tafinlar + Mekinist after surgical resection gives melanoma patients the chance for long-term relapse-free survival. Five years is a clinically and emotionally significant milestone for patients. Recurrent BRAF+ melanoma, once spread to other organs, can be more dangerous and difficult to treat. The durable, long-term results seen among patients in the COMBI-AD trial clearly point to the important role targeted therapy plays in the adjuvant setting."

The COMBI-AD study results are drawn from a prospective analysis of 870 patients with BRAF V600-mutated melanoma treated with Tafinlar + Mekinist after their surgery1. This study represents the largest collection of data and longest follow-up to date in this patient population treated with targeted therapy2. The findings were presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program (Abstract #10001)1.

"The five-year survival mark is an important and predictive milestone for people with melanoma and the doctors who care for them," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "We see an almost 50% risk reduction in melanoma relapse or death in the COMBI-AD data announced today, and we believe patients will find this information helpful in choosing a treatment after surgery. We thank the patients and their families who participated in this long-term clinical trial. Their participation and commitment is helping the community learn how a BRAF-targeted therapy can reimagine outcomes for patients with resectable stage III melanoma."

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program data presentations (for registered participants).

About the COMBI-AD Study1,2,6,7
COMBI-AD is a pivotaI Phase III study evaluating Tafinlar (dabrafenib) + Mekinist (trametinib) among patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy. It is the longest follow-up, at 60 months, and largest dataset to date of patients with Stage III melanoma receiving targeted therapy for adjuvant treatment.

It is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. Subjects were randomized to receive either dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) combination therapy or two placebos for up to one year. The primary end point is recurrence-free survival, and secondary endpoints include overall survival, distant metastasis-free survival, freedom from relapse analysis and safety.

Melanoma staging assessed based on AJCC guidelines version 7.

During the five-year follow-up, updated safety analyses were not performed because no patients remained on therapy during the extended follow‐up period.

About Melanoma
There are more than 285,000 new diagnoses of melanoma (Stages 0-IV) worldwide each year, approximately half of which have a BRAF mutation8,9. Genetic tests can determine whether a tumor has a BRAF mutation10.

One way melanoma is staged is by how far it has metastasized11. In stage III melanoma, tumors have spread to the regional lymph nodes, presenting a higher risk of recurrence or metastases11. Patients who receive surgical treatment for stage III melanoma may have a high risk of recurrence because melanoma cells may remain in the body after surgery12. Generally the majority of relapses in stage III melanoma occur within 5 years13. Patients should ask their doctor if they are at risk for melanoma returning12.

About Tafinlar + Mekinist Combination
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
That has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

TAFINLAR and MEKINIST are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

TAFINLAR and MEKINIST are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

that has spread to other parts of the body and you have no satisfactory treatment options and
that has a certain type of abnormal "BRAF" gene
TAFINLAR, in combination with MEKINIST, should not be used to treat people with wild-type BRAF melanoma. MEKINIST should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that TAFINLAR and MEKINIST, in combination, are right for you.

It is not known if TAFINLAR and MEKINIST are safe and effective in children.

TAFINLAR and MEKINIST, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When TAFINLAR is used in combination with MEKINIST, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

MEKINIST, alone or in combination with TAFINLAR, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

TAFINLAR, in combination with MEKINIST, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of TAFINLAR and MEKINIST can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

TAFINLAR, in combination with MEKINIST, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

TAFINLAR, in combination with MEKINIST, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with TAFINLAR in combination with MEKINIST, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of TAFINLAR in combination with MEKINIST. In some cases these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with TAFINLAR in combination with MEKINIST. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

TAFINLAR may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

TAFINLAR, in combination with MEKINIST, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with TAFINLAR and MEKINIST and for at least 4 months after the last dose of TAFINLAR and MEKINIST. For women of reproductive potential, TAFINLAR and MEKINIST, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with TAFINLAR and MEKINIST in combination, and for 4 months after stopping treatment with TAFINLAR and MEKINIST. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

On May 29, 2020 Novartis reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy (Press release, Novartis, MAY 29, 2020, View Source [SID1234558666]).

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"PIK3CA is the most commonly mutated gene in HR+/HER2- advanced breast cancer, affecting approximately 40% of patients. If approved, alpelisib has the potential to transform the way we treat this cancer in Europe, offering physicians a clear treatment for patients with a PIK3CA mutation that nearly doubles the time to disease progression," said Fabrice André, MD, PhD, research director and head of INSERM Unit U981, professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France, and global SOLAR-1 principal investigator.

The CHMP opinion is based on results of the Phase III SOLAR-1 trial that showed Piqray plus fulvestrant nearly doubled median progression-free survival (PFS) compared to fulvestrant alone in HR+/HER2- advanced breast cancer patients with tumors harboring a PIK3CA mutation (median PFS 11.0 months vs. 5.7 months; HR=0.65, 95% CI: 0.50-0.85; p<0.001), the study’s primary endpoint. PFS subgroup analyses demonstrated consistent efficacy in favor of Piqray, irrespective of presence or absence of lung/liver metastases.

"We are excited about today’s CHMP opinion, recommending the first and only treatment option for European patients specifically developed to target the PIK3CA mutation in their cancer," said Susanne Schaffert, PhD, President, Novartis Oncology. "Piqray is another example of how we are reimagining cancer care to bring new targeted therapies to patients with high unmet needs that help them live longer without disease progression."

In SOLAR-1, most adverse events were mild to moderate in severity and generally manageable through dose modifications and medical management. Of these, the most common grade 3/4 events (≥7%) were plasma glucose increased (39.1%), rash (19.4%), gamma-glutamyltransferase increased (12.0%), lymphocyte count decreased (9.2%), diarrhea (7.0%) and lipase increased (7.0%). No patients developed diabetes as a result of transient hyperglycemia.

The European Commission will review the CHMP recommendation and usually delivers a final decision within approximately two months. The decision will be applicable to all 27 European Union member states plus the United Kingdom, Iceland, Norway and Liechtenstein. Additional regulatory filings are underway with other health authorities worldwide.

Patients with HR+/HER2- advanced breast cancer should be selected for treatment with Piqray based on the presence of a PIK3CA mutation in tumor or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, tumor tissue should be tested if available.

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer, as detected by a validated test following progression on or after endocrine-based regimen. Piqray is approved in the U.S., and 12 other countries around the world.

About SOLAR-1
SOLAR-1 is a global, Phase III randomized, double-blind, placebo-controlled trial studying Piqray in combination with fulvestrant for postmenopausal women, and men, with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor1,2,3.

The trial randomized 572 patients. Patients were allocated based on central tumor tissue assessment to either a PIK3CA-mutated cohort (n=341) or a PIK3CA non-mutated cohort (n=231). Within each cohort, patients were randomized in a 1:1 ratio to receive continuous oral treatment with Piqray (300 mg once daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or placebo plus fulvestrant. Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment1,2,3. Patients and investigators are blinded to PIK3CA mutation status and treatment.

The primary endpoint is local investigator assessed PFS using RECIST 1.1 for patients with a PIK3CA mutation. The key secondary endpoint is overall survival, and additional secondary endpoints include, but are not limited to, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutated cohort, safety and tolerability1,2,3. SOLAR-1 is ongoing to assess overall survival and other secondary endpoints.

Piqray (alpelisib) Important Safety Information from the U.S. Prescribing Information
Patients should not take PIQRAY if they have had a severe allergic reaction to PIQRAY or are allergic to any of the ingredients in PIQRAY.

PIQRAY may cause serious side effects. PIQRAY can cause severe allergic reactions. Patients should tell their health care provider or get medical help right away if they have trouble breathing, flushing, rash, fever, or fast heart rate during treatment with PIQRAY. PIQRAY can cause severe skin reactions. Patients should tell their health care provider or get medical help right away if they get severe rash or rash that keeps getting worse, reddened skin, flu-like symptoms, blistering of the lips, eyes or mouth, blisters on the skin or skin peeling, with or without fever. PIQRAY can cause high blood sugar levels (hyperglycemia). Hyperglycemia is common with PIQRAY and can be severe. Health care providers will monitor patients’ blood sugar levels before they start and during treatment with PIQRAY. Health care providers may monitor patients’ blood sugar levels more often if they have a history of Type 2 diabetes. Patients should tell their health care provider right away if they develop symptoms of hyperglycemia, including excessive thirst, dry mouth, urinate more often than usual or have a higher amount of urine than normal, or increased appetite with weight loss. PIQRAY can cause lung problems (pneumonitis). Patients should tell their health care provider right away if they develop new or worsening symptoms of lung problems, including shortness of breath or trouble breathing, cough, or chest pain. Diarrhea is common with PIQRAY and can be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney problems. Patients who develop diarrhea during treatment with PIQRAY should tell their health care provider right away.

Before taking PIQRAY, patients should tell their health care provider if they have a history of diabetes, skin rash, redness of skin, blistering of the lips, eyes or mouth, or skin peeling, are pregnant, or plan to become pregnant as PIQRAY can harm their unborn baby. Females who are able to become pregnant should use effective birth control during treatment with PIQRAY and for 1 week after the last dose. Do not breastfeed during treatment with PIQRAY and for 1 week after the last dose. Males with female partners who are able to become pregnant should use condoms and effective birth control during treatment with PIQRAY and for 1 week after the last dose. Patients should also read the Full Prescribing Information of fulvestrant for important pregnancy, contraception, infertility, and lactation information.

Patients should tell their health care provider all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. PIQRAY and other medicines may affect each other causing side effects. Know the medicines you take. Keep a list of them to show your health care provider or pharmacist when you get a new medicine.

The most common side effects of PIQRAY when used with fulvestrant are rash, nausea, tiredness and weakness, decreased appetite, mouth sores, vomiting, weight loss, hair loss, and changes in certain blood tests.

On May 29, 2020 Kuraray Co., Ltd. (Head Office: Chiyoda-ku, Tokyo; President: Masaaki Ito; hereinafter "Kuraray") reported that it has published the Kuraray Report 2020, an integrated report (A4 size, 50 pages, full color) (Press release, Kuraray, MAY 29, 2020, View Source [SID1234558665]).
The aim of the Kuraray Report is to help shareholders, investors, and all other stakeholders better understand the value that the Kuraray Group creates over the medium to long term by providing a comprehensive overview of financial and non-financial information, including environmental, social and governance data.
Going forward, the Kuraray Group will continue to hold constructive dialogues with its stakeholders while also enhancing the content of the report.

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Overview of the Kuraray Report 2020
This report features Kuraray’s initiatives implemented under the medium-term management plan "PROUD 2020," with the close of the plan’s final year scheduled for December 31, 2020. The aim is to become a "Specialty Chemical Company growing sustainably by incorporating new foundational platforms into its own technologies"—the ideal described in "Kuraray Vision 2026," which sets out the Company’s aspirations from a long-term perspective. Also included in the report are sections focused on the foundations Kuraray has established to support new value creation in connection with environmental, social and governance issues.
To read the PDF version of this report, please click on the following link:

Sustainability Section of Kuraray’s Corporate Website
The sustainability section of Kuraray’s corporate website features detailed sustainability-related information not fully covered in the report. It also includes an explanation of Kuraray’s refreshed approach to sustainability based on its revised "Sustainability Concept," which outlines the Company’s areas of materiality, as well as articles on sustainability initiatives being carried out in countries overseas.
In addition, the site was created using responsive web design and can be easily viewed on a smart phone or tablet.
Moreover, the sustainability section offers reports created in line with the 2016 GRI Standards, international guidelines for sustainability reports.

On May 29, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion under conditional marketing authorisation for Rozlytrek (entrectinib) for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options (Press release, Hoffmann-La Roche, MAY 29, 2020, View Source [SID1234558664]). The CHMP has also recommended Rozlytrek for the treatment of adults with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.1

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"Once approved, Rozlytrek could become Roche’s first tumour-agnostic therapy in Europe," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This milestone therefore represents additional progress in personalised healthcare. Based on genomic testing, Rozlytrek provides an effective first-line treatment for many people whose cancers harbour NTRK or ROS1 gene fusions, including tumours that have progressed to the brain."

The positive CHMP opinion is based on results from the integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials, and data from the phase I/II STARTRK-NG study. Results showed:

Rozlytrek shrank tumours in more than half of people with NTRK fusion-positive, locally advanced or metastatic solid tumours (overall response rate [ORR]= 63.5%; N=74), and objective responses were observed across 14 tumour types (median duration of response [DoR] = 12.9 months [9.3 months – not reached], N=21 out of 47).2
In ROS1-positive, advanced NSCLC, Rozlytrek shrank tumours in 73.4% of people with the disease (ORR; N=94 with 12 months follow up), with a median DoR of 16.5 months (14.6 – 28.6 months). In a group of 161 patients with 6 months follow up, including 29% of patients with central nervous system (CNS) metastases at baseline, ORR was observed to be 67.1%.1
Objective responses to Rozlytrek were seen in people with CNS metastases at baseline, in both the NTRK and ROS1 populations.1,2
In paediatric patients, Rozlytrek shrank tumours (ORR) in all children and adolescents who had NTRK gene fusions (N=5), with two achieving a complete response (CR). Two patients with primary high-grade tumours in the CNS had objective responses, including one patient with a CR.1
Across these studies, Rozlytrek was evaluated in several solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.1,2

Rozlytrek was well tolerated. The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (oedema), dizziness, diarrhoea, nausea, nervous system disorders (dysaesthesia), shortness of breath (dyspnoea), anaemia, increased weight, increased blood creatinine, pain, cognitive disorders, vomiting, cough, and fever (pyrexia).1,2

Rozlytrek has been granted Priority Medicines (PRIME) designation by the EMA 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 who have no acceptable standard therapies.1 A final decision regarding the approval of Rozlytrek by the European Commission is expected in the coming months.

Biomarker testing for NTRK gene fusions and ROS1 in NSCLC across all solid tumours is the only way to identify people who are most eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, in conjunction with Foundation Medicine, to develop a companion diagnostic that will help identify people with NTRK and ROS1 gene fusions.

About the integrated analysis
The CHMP recommendation is based on an integrated analysis including data from 74 people with locally advanced or metastatic NTRK fusion-positive solid tumours (14 tumour types) and 161 people with ROS1-positive NSCLC from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials.1,2 It is also based on data from the phase I/II STARTRK-NG study in paediatric patients.1 The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 504 people across these four trials.1,2

About NTRK fusion-positive cancer
NTRK fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signalling pathways involved in the proliferation of certain types of cancer.3 NTRK gene fusions are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.2

About ROS1-positive NSCLC
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.4

ROS1 gene fusions account for 1-2% of non-small-cell lung cancer (NSCLC).4 Lung cancer is the leading cause of cancer-related death across the world.5 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.5 NSCLC is the most common type of lung cancer and accounts for up to 85% of all lung cancer diagnoses.6 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.4

About Rozlytrek
Rozlytrek (entrectinib) is a tumour-agnostic, once-daily oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.7,8 Rozlytrek can block NTRK and ROS1 kinase activity and may result in the death of cancer cells with NTRK or ROS1 gene fusions.7,8

Rozlytrek was granted accelerated approval in August 2019 by the US Food and Drug Administration (FDA), following receipt of Breakthrough Therapy designation, for the treatment of adult and paediatric patients 12 years of age and older with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy, and was approved for the treatment of adults with ROS1-positive, metastatic NSCLC. In June 2019, Rozlytrek was also approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult and paediatric patients with NTRK fusion-positive, advanced recurrent solid tumours, and was later approved in ROS1 positive NSCLC in February 2020. Rozlytrek has also received approvals by health authorities in Australia, Canada, Hong Kong, Israel and South Korea.1

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On May 29, 2020 Exact Sciences Corp. (NASDAQ: EXAS) reported it is presenting new data at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO20) Virtual Scientific Program (Press release, Exact Sciences, MAY 29, 2020, View Source [SID1234558663]). These data further demonstrate the clinical value of the Oncotype DX Breast Recurrence Score test and exemplify the research progress made by Exact Sciences’ Mayo Clinic collaboration toward smarter solutions across the cancer continuum.

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Three studies of the Oncotype DX Breast Recurrence Score test presented at ASCO (Free ASCO Whitepaper)20 highlight the value that the Oncotype DX test can provide by personalizing and improving neoadjuvant treatment decisions (i.e., prior to surgery) in women with hormone receptor positive, HER2-negative breast cancer.

The new data at ASCO (Free ASCO Whitepaper)20 add to existing evidence1,2,3 and reinforce the value of the Oncotype DX test in light of recent COVID-19 pandemic recommendations.4,5

"As health systems across the world respond to the COVID-19 pandemic, both cancer screenings and elective surgeries are being postponed," said Dr. Anthony Lucci, professor of Breast Surgical Oncology at MD Anderson Cancer Center. "Based on the new data presented at ASCO (Free ASCO Whitepaper)20, the Oncotype DX test identified women with a low likelihood of responding to neoadjuvant chemotherapy, who may benefit from alternative approaches while awaiting surgery, such as neoadjuvant endocrine therapy at home. This approach could overcome some of the unique challenges we and our patients are currently facing during this public health crisis."

Response to neoadjuvant chemotherapy and the 21-gene Breast Recurrence Score in young women with estrogen receptor-positive early breast cancer
Abstract Number: 514
This study included 76 women treated with neoadjuvant chemotherapy from the Young Women’s Breast Cancer Study, a multi-center prospective group of women diagnosed with breast cancer at age 40 or younger. The Oncotype DX test was performed on tumor specimens from core biopsies obtained from the patients prior to surgery. Results revealed that patients with a higher Recurrence Score result were more likely to achieve a pathologic complete response (pCR; no residual invasive tumor) with chemotherapy.

21-gene Recurrence Score assay as a predictor of pathological response in neoadjuvant chemotherapy administration for ER-positive/HER2-negative early-stage breast cancer
Abstract Number: e12630
Conducted in Spain, this study prospectively analyzed a group of 63 patients who received neoadjuvant chemotherapy after the Oncotype DX test was performed on tumor specimens from core biopsies. The analysis showed a strong correlation between pCR and Recurrence Score result. In particular, the Recurrence Score result was the most significant predictor of pCR when compared to other factors such as Ki67 (a classic prognostic factor), estrogen receptor status, and initial tumor size.

Prediction of response to neoadjuvant hormonal therapy (NAHT) using upfront Oncotype DX Breast Recurrence Score (RS): results from the SAFIA phase III trial
Abstract Number: 594
In this study, the Oncotype DX test was performed prior to surgery and patients with Recurrence Score results 0-30 received neoadjuvant endocrine therapy without chemotherapy. After four months of treatment, data from 142 patients showed that 97% of them had a clinical response or stable disease, suggesting that patients with a Recurrence Score result <31 can be offered neoadjuvant endocrine therapy alone with minimal risk of progression of disease.

Additional Abstracts Highlight Progress in Research and Development

Through a longstanding collaboration, researchers at Exact Sciences and Mayo Clinic continue to identify biomarkers associated with some of the deadliest forms of cancer. Abstracts accepted for presentation at ASCO (Free ASCO Whitepaper)20, including promising results in five different cancer types, are highlighted below.

Algorithm for blood-based panel of methylated DNA and protein markers to detect early-stage hepatocellular carcinoma (HCC) with high specificity
Abstract Number: 4577
A robust algorithm based on novel blood-based biomarkers provided higher sensitivity for early-stage HCC (70%) compared to other available blood-based methods (54% and 52%) and, therefore, could significantly impact HCC clinical management and patient outcomes.

Molecular detection of pancreatic neuroendocrine tumors using methylated DNA markers: discovery and tissue validation
Abstract Number: e16705
Four novel methylated DNA markers accurately discriminated pancreatic neuroendocrine tumors from controls with normal pancreas and buffy coat (≥ 95% accuracy for each marker). These markers also differentiated metastatic pancreatic neuroendocrine tumors from normal pancreas tissue.

Novel methylated DNA markers in plasma detect distant recurrence of colorectal cancer
Abstract Number: 4088
A panel of novel methylated DNA markers in plasma detected distant recurrent colorectal cancer with promising accuracy (96% in liver metastases, 78% in lung metastases, and 57% in peritoneal/nodal metastases). These data are a positive early signal for the clinical utility of methylated DNA markers for non-invasive post-treatment surveillance and treatment monitoring in colorectal cancer.

Methylated DNA markers for plasma detection of ovarian cancer: discovery, validation, and clinical feasibility
Abstract Number: 6072
Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate methylated DNA markers for ovarian cancer that performed with promisingly high sensitivity and specificity in plasma (79% sensitivity at 96% specificity). These data indicate that larger plasma-based ovarian cancer methylated DNA marker testing studies are warranted.

Methylated DNA marker panel for metastatic melanoma: discovery and tissue validation
Abstract Number: e22024
A panel of five novel methylated DNA markers assayed on tissue and undetectable in normal buffy coat achieved a very high discrimination between melanoma and benign control tissues (94% for metastatic melanoma and 85% for primary melanoma). This panel can be assessed in blood or other bodily fluids for application in melanoma surveillance.

ASCO20 will be conducted May 29-31, 2020.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Exact Sciences. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.