On January 27, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the completion of a supplemental Biologics License Application (sBLA) submission to the US Food and Drug Administration (FDA) for Tecentriq (atezolizumab) in combination with Avastin (bevacizumab), for the treatment of people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Hoffmann-La Roche, JAN 27, 2020, View Source [SID1234553548]). The FDA is reviewing the application under the Real-Time Oncology Review pilot programme, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. In July 2018, the FDA granted Breakthrough Therapy Designation for Tecentriq in combination with Avastin in HCC based on data from an ongoing Phase Ib trial.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Liver cancer is the most rapidly increasing cause of cancer-related death in the United States. In the IMbrave150 study, Tecentriq in combination with Avastin became the first treatment in more than a decade to improve overall survival compared with the current standard of care," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We are pleased that these results are being reviewed under the FDA Real-Time Oncology Review pilot programme, and we are working closely with the agency to bring this potential new treatment option to people with unresectable hepatocellular carcinoma as quickly as possible."

This application is based on the results of the Phase III IMbrave150 study, which demonstrated that Tecentriq in combination with Avastin reduced the risk of death (overall survival; OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease worsening or death (progression-free survival; PFS) by 41% (HR=0.59; 95% CI: 0.47–0.76; p<0.0001), compared with sorafenib. Safety for Tecentriq and Avastin was consistent with the known safety profiles of the individual medicines. The results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress in November 2019.

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

About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who had not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

The two primary endpoints were OS and PFS by independent review facility (IRF) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Additional study endpoints included overall response rate (ORR) and duration of response (DoR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (including time to deterioration of patient-reported quality of life), safety and pharmacokinetics.

About hepatocellular carcinoma
HCC, the most common form of liver cancer, is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.1 Every year, more than 750,000 people worldwide are diagnosed with HCC,1,2 with the majority of cases in Asia and almost half of all cases in China.2,3 In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise.4–6 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1 The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.7

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration, and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
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 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 metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

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.

On January 27, 2020 AstraZeneca’s and Daiichi Sankyo Company, Limited reported that High-level results from the positive registrational Phase II trial DESTINY-Gastric01 showed (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan), achieved a statistically significant and clinically meaningful improvement in objective response rate (ORR) and overall survival (OS) in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed following two or more treatment regimens including trastuzumab and chemotherapy (Press release, AstraZeneca, JAN 27, 2020, View Source [SID1234553546]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The trial met its primary endpoint of an improvement in ORR, as assessed by an independent review committee, in patients treated with Enhertu compared to investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy). Enhertu also showed a statistically significant and clinically meaningful improvement in OS, a key secondary endpoint.

José Baselga, Executive Vice President, Oncology R&D, said: "Gastric cancer is usually diagnosed in the advanced stage and patients face markedly high mortality rates, making the need for new therapies especially urgent. Given the previous results seen in our HER2-positive development programme and now in HER2-positive metastatic gastric cancer, we believe this antibody drug conjugate has the potential to redefine the treatment of patients with HER2-expressing cancers."

Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: "We are excited to report positive top-line results from this trial. Our development plan remains on track in gastric cancer, including an initial regulatory application in Japan where gastric cancer is highly prevalent, and where SAKIGAKE designation has been granted for this indication. We are strongly committed to bringing this therapy as rapidly as possible to patients in need."

The overall safety and tolerability profile of Enhertu in DESTINY-Gastric01 was consistent with that seen in the published Phase I trial in which the most common adverse events (≥30 percent, any grade) were haematologic and gastrointestinal including neutrophil count decrease, anaemia, nausea and decreased appetite. There were cases of treatment-related interstitial lung disease (ILD) and pneumonitis, the majority of which were Grade 1 and 2 with two Grade 3 and one Grade 4. No ILD-related deaths (Grade 5) occurred in gastric patients in the Phase I trial or in the DESTINY-Gastric01 trial.

These results confirm activity seen in the non-randomised Phase I trial of Enhertu in patients with HER2-positive advanced gastric cancer published in The Lancet Oncology.1 Data from DESTINY-Gastric01 will be presented at a forthcoming medical meeting.

In addition to the planned discussion with the Japan Ministry of Health, Labour and Welfare (MHLW), both companies plan to discuss the data with other health authorities. Enhertu recently received Accelerated Approval in the US for HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based treatment regimens and additional global regulatory submissions in HER2-positive metastatic breast cancer are underway.

Enhertu is being jointly developed and commercialised worldwide with AstraZeneca except in Japan where Daiichi Sankyo maintains exclusive rights.

HER2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including gastric, breast and lung cancers. HER2 overexpression is often associated with aggressive disease and poorer prognosis.2 When a patient is diagnosed with gastric cancer, guidelines recommend evaluating HER2-expression levels by an immunohistochemistry (IHC) test.3 A finding of IHC 3+ is considered positive. A result of IHC 2+ is considered equivocal, in which case an additional testing method of in situ hybridisation (ISH) is recommended to confirm HER2 status.

Gastric cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality; there were approximately one million new cases reported in 2018 and 783,000 deaths.4 Incidence rates for gastric cancer are markedly higher in eastern Asia, where approximately half of all cases occur.4 South Korea and Japan have the first and third highest incidence rates of gastric cancer worldwide, respectively; in 2018, the age-standardised rate in Japan was 27.5 per 100,000 and in South Korea it was 39.6 per 100,000.5

Approximately one in five gastric cancers are HER2 positive.6 Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.7 Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy.8 For gastric cancer that progresses on trastuzumab, there are no other approved HER2-targeting medicines and subsequent treatment options are limited.9

DESTINY-Gastric01

DESTINY-Gastric01 is a registrational Phase II, open-label, multi-centre trial assessing the safety and efficacy of Enhertu in 189 patients from Japan and South Korea with HER2-expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior treatment regimens including fluoropyrimidine (5-FU) and platinum chemotherapy and trastuzumab. Patients were randomised 2:1 to receive Enhertu or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy given on the same schedule. The primary endpoint of the trial is ORR. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints.

Enhertu

Enhertu (fam-trastuzumab deruxtecan-nxki in the US only; trastuzumab deruxtecan outside the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Enhertu clinical development

A comprehensive development programme is underway globally with five registrational trials in HER2-expressing metastatic breast and gastric cancers including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On January 25, 2020 Taiho Oncology, Inc. reported the presentation of a pooled analysis for hematologic adverse events of the global Phase III TAGS and RECOURSE trials evaluating LONSURF (trifluridine and tipiracil) in patients with metastatic colorectal cancer (mCRC) and metastatic gastric or gastroesophageal junction cancer (mGC/GEJC), respectively (Press release, Taiho, JAN 25, 2020, View Source [SID1234553541]). The company also presented updates on two trials in progress with futibatinib, the Phase III FOENIX-CCA3 study of futibatinib as first-line treatment for patients with advanced cholangiocarcinoma (CCA) harboring FGFR 2 gene rearrangements and a Phase II basket study of futibatinib in patients with advanced solid tumors harboring FGFR genomic aberrations.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These data were highlighted at the ASCO (Free ASCO Whitepaper) 2020 Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco on January 23-25, 2020.

LONSURF Pooled Safety Analysis
The pooled safety analysis of the TAGS and RECOURSE trials determined that hematologic adverse events with LONSURF in subgroups of patients with mild to moderate renal impairment and mild hepatic impairment were manageable and similar to those in the overall patient population.

"Beyond the therapeutic effects of treatment and its impact on disease progression and survival in people living with cancer, the safety and tolerability of our medicines are the highest priority to us," said Karin Blakolmer, MD, MBA, Senior Vice President and Head of Medical Affairs, Taiho Oncology, Inc. "For patients treated with LONSURF in the TAGS and RECOURSE trials, we are pleased to see that hematologic adverse events for certain subgroups were in line with what we saw in the overall patient population and, as important, were manageable. This is good news for people living with metastatic colorectal cancer and metastatic gastric cancer who are receiving treatment with LONSURF."

Futibatinib Trials in Progress
The first trial in progress is FOENIX-CCA3, a Phase III multicenter, open-label, randomized study that will be conducted in patients with metastatic or unresectable intrahepatic CCA harboring FGFR2 rearrangements. Approximately 216 patients will be randomized to receive first-line therapy with 20 mg futibatinib once daily or gemcitabine and cisplatin for up to 8 cycles. Patients are to be treated until the first occurrence of disease progression, death or other protocol specified discontinuation criteria. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR) and disease control rate and safety.

The second trial in progress is a Phase II global, open-label study that will explore treatment with futibatinib in patients (n=~60) with metastatic or locally advanced solid tumors, except primary brain tumors or intrahepatic CCA, harboring FGFR1–4 rearrangements and with disease progression after standard treatment (Cohort A), and in patients (n=~35) with metastatic or locally advanced gastric tumors harboring FGFR2 amplifications and with two or more lines of prior therapy (Cohort B). Patients will receive 20 mg of futibatinib once daily in a continuous 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. The primary endpoint is independently assessed ORR. Secondary endpoints include ORR per investigator, disease control rate, duration of response, PFS, overall survival and safety.

About TAGS
The TAGS (TAS-102 Gastric Study) trial was a Taiho-sponsored, global, pivotal Phase III, multinational, randomized, double-blind study evaluating LONSURF (trifluridine and tipiracil, FTD/TPI), plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic gastric cancer, including gastroesophageal junction cancer, refractory to standard treatments. The primary endpoint in the TAGS trial was overall survival (OS), and the main secondary endpoint measures included progression-free survival (PFS), safety and tolerability, as well as quality of life.

The TAGS trial enrolled 507 adult patients with metastatic gastric cancer who had previously received at least two prior regimens for advanced disease. The study was conducted in 17 countries and 110 sites around the world.

About RECOURSE
The RECOURSE trial was a global, randomized, double-blind, placebo-controlled Phase III comparison trial evaluating the efficacy and safety of orally administered LONSURF in patients with previously treated mCRC. The trial enrolled 800 patients in North America, Japan, Europe and Australia. Patients were randomized (2:1) to receive LONSURF (35 mg/m2) or placebo, plus BSC, twice daily. The study met its primary and secondary endpoints of OS and PFS versus placebo.

About Metastatic Colorectal Cancer
Colorectal cancer is the 4th most commonly diagnosed cancer in the United States (U.S.).1 In 2019, there were an estimated 145,600 new cases and 51,020 deaths in the U.S.1 Approximately 22 percent of U.S. patients with colorectal cancer are diagnosed at the distant or metastasized stage.1 Metastatic colorectal cancer (mCRC) is associated with poor prognosis with a five-year survival rate of approximately 14 percent.1

Over the last decade, clinical outcomes for patients with mCRC have improved considerably due to the advent of novel treatment agents, predictive biomarkers, and a more strategic approach to the delivery of systemic therapies. Currently, the median overall survival for patients with mCRC being treated both in Phase III trials and in large observational series or registries is 30 months – more than double that of 20 years ago.2,3,4

About Cholangiocarcinoma

Cholangiocarcinoma (CCA), also known as bile duct cancer, is not common. About 8,000 people in the U.S. are diagnosed with CCA each year.5 This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) cancers. CCA can occur at younger ages, but it is seen mainly in older people. The average age of people in the U.S. diagnosed with cancer of the intrahepatic bile ducts is 70, and for cancer of the extrahepatic bile ducts it is 72.5 The chances of survival for patients with CCA depend to a large extent on its location and how advanced it is when it is found.5

The main treatment for CCA is surgery. Radiation therapy and chemotherapy may be used if the cancer cannot be entirely removed with surgery and in cases where the edges of the tissues removed at the operation show cancer cells (also called a positive margin). Both stage III and stage IV cancers cannot be completely removed surgically. Currently, standard treatment options are limited to radiation, palliative therapy, liver transplantation, surgery, chemotherapy and interventional radiology.6

About Metastatic Gastric Cancer
Gastric cancer, also known as stomach cancer, is the 15th most commonly diagnosed cancer in the U.S.7 In 2019, there were an estimated 27,510 new cases and 11,140 deaths. Approximately 62 percent of U.S. patients with gastric cancer are diagnosed at advanced disease. Metastatic gastric cancer (mGC) is associated with a five-year survival rate of about 5 percent.7

In the U.S., standard chemotherapy regimens for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. After failure of first- and second-line therapies, subsequent treatment options are limited.

About Gastroesophageal Junction Cancer
Gastroesophageal junction cancer is a type of cancer that begins in cells located near the gastroesophageal junction, the area where the esophagus connects to the stomach.8 It remains a significant clinical problem that is increasing in incidence and is associated with a poor prognosis. The majority of patients present with advanced disease, and less than 50 percent undergo curative treatment.9

About Futibatinib (TAS-120)
Futibatinib (TAS-120) is an investigational, oral, potent, selective, and irreversible small-molecule inhibitor of FGFR1, 2, 3, and 4 being studied as a potential treatment for patients with advanced solid tumors, including cholangiocarcinoma, who were previously treated with chemotherapy or other therapies including other FGFR inhibitors. Futibatinib selectively and irreversibly binds to the ATP binding pocket of FGFR 1-4 resulting in the inhibition of FGFR-mediated signal transduction pathways, reduced tumor cell proliferation and increased tumor cell death in tumors with FGFR1-4 genomic aberrations.

About LONSURF10

LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation.

Since 2015, Taiho Pharmaceutical and Servier have been in an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico, and Asia.

Indications and Use
LONSURF is indicated for the treatment of adult patients with:

metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy
metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression:

LONSURF caused severe and life‑threatening myelosuppression (Grade 3‑4) consisting of neutropenia (38%), anemia (18%), thrombocytopenia (5%), and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection. A total of 12% of LONSURF‑treated patients received granulocyte‑colony stimulating factors. Obtain complete blood counts prior to and on day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, absolute neutrophil count less than 500/mm3, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose as clinically indicated.

Embryo‑Fetal Toxicity:

LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breast‑fed infant or the effects on milk production. Because of the potential for serious adverse reactions in breast‑fed infants, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age or over who received LONSURF had a higher incidence of the following compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4 thrombocytopenia (7% vs 4%).

Hepatic Impairment: Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin greater than 1.5 times ULN and any AST) hepatic impairment. Patients with severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST) were not studied. No adjustment to the starting dose of LONSURF is recommended for patients with mild hepatic impairment.

Renal Impairment: No adjustment to the starting dosage of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m2.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in Patients Treated With LONSURF (≥5%): The most common adverse drug reactions in LONSURF‑treated patients vs placebo‑treated patients with mCRC, respectively, were asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), infections (27% vs 16%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%). In metastatic gastric cancer or gastroesophageal junction (GEJ), the most common adverse drug reactions, respectively were, nausea (37% vs 32%), decreased appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs 16%) and diarrhea (23% vs 14%).

Pulmonary emboli occurred more frequently in LONSURF‑treated patients compared to placebo: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

Laboratory Test Abnormalities in Patients Treated With LONSURF: The most common laboratory test abnormalities in LONSURF‑treated patients vs placebo-treated patients with mCRC, respectively, were anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%). In metastatic gastric cancer or GEJ, the test abnormalities, respectively, were neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia (34% vs 9%).

On January 25, 2020 NantHealth, Inc.(NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported Results of a fifty-gene breast cancer RNA subtype classifier applied to 167 colorectal cancer (CRC) patients during a poster session at the 2020 Gastrointestinal Cancer Symposium sponsored by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, NantHealth, JAN 25, 2020, View Source [SID1234553531]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Symposium, held at the Moscone West Building in San Francisco, CA from January 23-25, provides evidence-based teaching methods and cutting-edge learning science to a diverse audience of leaders in oncology education, doctors and care teams.

NantHealth’s presentation utilized data on whole exome (WES) DNA tumor and paired germline and matched deep whole transcriptomic sequencing (RNA-Seq) to identify a higher percentage of CRC patients with HER2 signaling than conventional methods of immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH). ERBB2 (HER2) gene expression was evaluated using NantOmics Nant50 gene classifier, which separates patients into subgroups that have been well established in breast cancer. The application of this tool to colorectal cancer proved surprising with greater than expected HER2 positive patients with a normally expected distribution of CMS classification (consensus molecular subtype in CRC). This finding suggests a possible utility for this tool in a new clinical setting. In addition, the HER2 enriched group did not show differentially expressed mutations in other targetable genes such as PIK3CA and BRAF, highlighting the potential importance of HER2 targeting in this population.

"Our analysis shows that conventional testing methods may miss potentially actionable HER2 signaling in CRC patients," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth. "The significant difference suggests that up to 40% more patients may be eligible for HER2 directed therapies, which has implications for drug development and clinical trials."

Title: "Results of a fifty-gene breast cancer RNA subtype classifier applied to 167 colorectal cancer (CRC) patients"

Authors: Sandeep K. Reddy, M.D., Tara Elisabeth Seery, M.D., Christopher W. Szeto, Ph.D.

Poster Session and Number: Poster session C (Board #A14)

Location: Moscone West Building

Date and Time: January 25, 2020, 6:30-7:55 AM PT and 12:15-1:45 PM PT

On January 25, 2020 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported new real-world data on treatment patterns for patients with advanced colorectal cancer (CRC) during a poster session at the 2020 Gastrointestinal Cancer Symposium sponsored by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, NantHealth, JAN 25, 2020, View Source [SID1234553530]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Symposium, held at the Moscone West Building in San Francisco, CA from January 23-25, provides evidence-based teaching methods and cutting-edge learning science to a diverse audience of leaders in oncology education, doctors and care teams.

NantHealth’s presentation examined therapeutic preferences and treatment patterns among advanced CRC patients using data from NantHealth’s Eviti Connect, an evidence-based treatment intelligence and web-based oncology decision support platform. Detailed information from 6,325 treatment plans was analyzed to identify treatment patterns using regorafenib and trifluridine + tipiracil for advanced CRC patients as third-line of therapy. National Comprehensive Cancer Network (NCCN) guidelines state that regorafenib and trifluridine+tipiracil are both treatment options for patients who have progressed through all available regimens.

Across all 6,325 treatment plans submitted for this patient population, regorafenib (n=217) or trifluridine+tipiracil (n=144) was the submitted treatment in 361 (5.5%) of the treatment plans, making them the 9th and 13th most frequently requested drugs (excluding growth factors, anti-emetics, and leucovorin) in this setting. While the total number of treatment plans for regorafenib was higher than that for trifluridine+tipiracil, the submission of trifluridine+tipiracil has increased over time, consistent with the latter drug’s more recent introduction into the market.

"Our analysis shows that recycling of chemotherapy and biologics in the late line setting is common and occurs more frequently than switching to a drug regimen with an alternative mechanism of action," said William A. Flood, MD, MS, Chief Medical Officer for Eviti, NantHealth. "As results cannot be fully explained by clinical trial outcome differences, NCCN guidelines preferences, or HEOR measures, we must delve deeper into why these therapeutic patterns exist to further our mission of optimizing patient outcomes and enabling value-based care in oncology. The uncertainty of what constitutes the ‘best’ treatment for this patient population provides an excellent opportunity to employ available data to guide patient-centered decision making and value-based care initiatives."

Title: "Real world data on treatment patterns of advanced CRC in 3rd line and beyond"

Authors: William A. Flood MD MS, Neil Margolis Ph.D., Vlad Kozlovsky, Sandeep K. Reddy MD

Abstract #56, Poster Session and Number: C – Anal and Colorectal Cancer

Location: Moscone West Building, Level 1, West Hall

Date and Time: January 25, 2020, 6:30-7:55 AM PT and 12:15-1:45 PM PT

"Our Eviti platform enables access to near-real time data on physician behavior which can provide unique and critical information to pharma, payers, and provider networks to optimize treatment strategies," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth.