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.

On May 29, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported the presentation of quality of life and certain safety results from the INVICTUS pivotal Phase 3 study evaluating QINLOCK (ripretinib) in adult patients with fourth-line advanced gastrointestinal stromal tumor (GIST) (Press release, Deciphera Pharmaceuticals, MAY 29, 2020, View Source [SID1234558662]). These results were presented as part of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program.

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"The recent FDA approval of QINLOCK marked an important milestone for the entire GIST patient community who had been waiting for a new treatment option designed specifically for their disease," said Matthew Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "In addition to the impressive efficacy results shown in the INVICTUS Phase 3 study, QINLOCK was shown to have a favorable safety profile. Today’s ASCO (Free ASCO Whitepaper) presentations demonstrate that patients receiving QINLOCK rated their overall health, quality of life, and physical and role function as better than that of patients receiving placebo. These insights into the GIST patient experience are invaluable to us as we establish a new standard of care in this area of unmet medical need."

Quality of Life and Self-Reported Function

In a poster presentation titled, "Quality of life (QoL) and self-reported function with ripretinib in ≥4th-line therapy for patients with gastrointestinal stromal tumors (GIST): Analyses from INVICTUS" (abstract 11535; poster 423), five key measures of quality of life and function were maintained in patients with fourth-line GIST receiving QINLOCK compared with declining measures in patients receiving placebo. Patients in the QINLOCK arm had consistently stable patient reported outcomes (PROs), and the measures suggest these patients were able to maintain quality of life while PROs declined sharply in the placebo arm. Additional highlights from the presentation include:

QINLOCK was associated with an increase in the patients’ self-reported health status on the EuroQol-5D visual analogue scale (EQ-5D-5L VAS) while placebo was associated with a decline (p=0.004).
Patients receiving QINLOCK reported better physical and role functioning on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) compared with a decline observed in patients receiving placebo (p=0.004; p=0.001).
Patients receiving QINLOCK had higher perceptions of their overall health and quality of life compared with patients receiving placebo (both p=0.001).
Differences between treatment arms were clinically significant (using threshold for meaningful change).
Patients receiving QINLOCK reported stable scores on all PRO measures out to cycle 10.
Safety and Impact on Patient Reported Outcomes

In a poster presentation titled, "Safety profile of ripretinib, including impact of alopecia and palmar-plantar erythrodysesthesia syndrome (PPES) on patient reported outcomes (PROs), in ≥4th-line advanced gastrointestinal stromal tumors (GIST): Analyses from INVICTUS" (abstract 11539; poster 427), when stratified by alopecia and PPES, patient-reported assessments of function, overall health, and overall quality of life were shown to be stable. This exploratory analysis demonstrates that alopecia and PPES were not associated with a negative effect on function, overall health, and quality of life. Additional highlights from the presentation include:

For both alopecia and PPES, the majority of the events were of lower severity grades and did not generally worsen over time.
In the QINLOCK arm, grade 1-2 alopecia occurred in 44 patients (52%) and grade 1-2 PPES occurred in 18 patients (21%). No patients experienced grade 3 or higher PPES.
There were no serious adverse events of alopecia or PPES reported.
In the QINLOCK arm, 8.2%, 24%, and 7.1% of patients experienced a treatment-emergent adverse event leading to treatment discontinuation, dose interruption, or dose reduction compared with 12%, 21%, and 2.3% in the placebo arm.
A copy of each presentation is available at www.deciphera.com/science/presentation-publications/.

About QINLOCK (ripretinib)

Indications and Usage

QINLOCK (ripretinib) is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. For more information visit QINLOCK.com.

Important Safety Information

There are no contraindications for QINLOCK.

Palmar-plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who received QINLOCK. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold QINLOCK and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received QINLOCK with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue QINLOCK at the same dose.

Hypertension: In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received QINLOCK. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating QINLOCK and during treatment, as clinically indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: QINLOCK can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. QINLOCK may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of QINLOCK in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong CYP3A inducers.

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About the INVICTUS Phase 3 Study

INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).