On January 15, 2020 The HealthWell Foundation, an independent non-profit that provides a financial lifeline for inadequately insured Americans, reported that it has opened a new fund to provide copayment and premium assistance to Medicare patients living with small cell lung cancer (SCLC) (Press release, HealthWell Foundation, JAN 15, 2020, View Source [SID1234553247]). Through the fund, HealthWell will provide up to $8,000 in financial assistance for a 12-month grant period to eligible patients who have annual household incomes up to 500 percent of the federal poverty level.

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About Small Cell Lung Cancer (SCLC)

SCLC, a type of neuroendocrine tumor, typically starts in the bronchi, the major airways in the center of the chest that lead to the lungs. SCLC is an aggressive cancer that grows and spreads rapidly, according to LUNGevity, a leading national lung cancer organization. SCLC represents approximately 15 percent of all lung cancers and about two-thirds of those diagnosed have extensive-stage disease, cancer that has metastasized or spread to other lymph nodes or organs, at the time of diagnosis. Treatment options vary depending on the stage of the disease and typically include one or more types of therapy, such as surgery, chemotherapy, radiation therapy or palliative care.

"A lung cancer diagnosis can leave patients feeling overwhelmed and worried about next steps in managing their condition. Many patients, especially those on Medicare, are concerned about their treatment options and whether they will be able to afford the proper care," said Katie Brown, OPN-CG, Vice President Support and Survivorship Programs at LUNGevity. "Eliminating as much stress as possible is critical to overall wellbeing and positive outcomes when navigating a lung cancer diagnosis. We applaud the HealthWell Foundation for recognizing the financial challenges people living with small cell lung cancer face and for assisting this patient community in accessing critical medical treatments without the stress of having to worry about covering the cost of their treatments."

"A diagnosis of small cell lung cancer can be devastating for the patient and their family. Treatment options often consist of chemotherapy and radiation, high-cost therapies that can create financial hardship and additional stress, especially for those on Medicare," stated HealthWell Foundation President, Krista Zodet. "We are honored that our dedicated donors understand the underlying challenges SCLC patients and their families face in accessing and affording treatment. We are excited to be able to assist Medicare patients living with SCLC with their out-of-pocket treatment costs and to be able to relieve some of the financial burden associated with those costs."

To determine eligibility and apply for financial assistance, visit HealthWell’s Small Cell Lung Cancer Fund page. To learn how you can support this or other HealthWell programs, visit HealthWellFoundation.org.

On January 15, 2020 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that the first patient has been dosed in a Phase 2 study evaluating the investigational agent alvocidib, a potent CDK9 inhibitor, in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with a hypomethylating agent (HMA) (Press release, Tolero Pharmaceuticals, JAN 15, 2020, View Source [SID1234553246]). The open-label, randomized study has two parts and will evaluate the safety and efficacy of alvocidib in monotherapy or in combination with low-dose cytarabine.

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"Patients with AML who are resistant to or progressed following treatment with the BCL-2 inhibitor venetoclax in combination with an HMA have limited treatment options, and it has been well established in the literature that a key potential mechanism of resistance to BCL-2 targeted therapy is the switch to a dependence on MCL-1," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "The initiation of this study marks an important step toward understanding the potential of alvocidib as a monotherapy or in combination with low-dose cytarabine for these patients. We believe that patients whose cancers have progressed following treatment with venetoclax may be sensitive to alvocidib and this trial will help us to better understand this hypothesis."

The primary objective of the Phase 2 study is to determine the rate of combined complete remission (CR) and CR with incomplete hematological recovery (CRi), of alvocidib and alvocidib in combination with low-dose cytarabine in patients with AML. Secondary objectives include establishing the recommended treatment regimen for the second part of the study and evaluating the median overall survival (mOS) and CR rate. Additional secondary outcome measures include evaluating event-free survival (EFS), duration of composite CR (CRc), safety and tolerability of the regimen and mortality.

In the first part of the study, patients who are refractory to or have relapsed on venetoclax in combination with an HMA will be randomized into two arms. In Arm 1 of the study, patients will receive combination therapy of alvocidib and low-dose cytarabine. In Arm 2 of the study, patients will receive alvocidib monotherapy. In the second part of the study, patients will receive the regimen based on the outcome of the first part.

The trial is being conducted at sites in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03969420).

About Alvocidib
Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the Phase 2 studies, Zella 202 in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with azacytidine or decitabine (NCT03969420) and Zella 201 in patients with relapsed or refractory MCL-1 dependent AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase 1 clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with cytarabine and daunorubicin (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with decitabine (NCT03593915). In addition, alvocidib is being evaluated in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1
MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.1 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.2 MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.1,3 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).4,5 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.4 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.1

On January 15, 2020 Natera, Inc. (NASDAQ: NTRA) reported an agreement with the National Cancer Center (NCC) Japan to launch the CIRCULATE-IDEA trial in Japan, a prospective, multi-center, randomized trial to investigate ctDNA-guided treatment strategies for patients with Stage II-III colon cancer, based on the results of molecular residual disease (MRD) testing with Signatera (Press release, Natera, JAN 15, 2020, View Source [SID1234553245]). The trial is organized by the NCC and national in scope, and it is expected to include approximately 1500 patients from over 100 cancer centers across Japan.

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The CIRCULATE-IDEA trial was unveiled in September 2019 at the annual congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper),1 introduced as a sequel to the pivotal IDEA collaboration of 2007-2017 which compared outcomes from 3 months vs. 6 months of adjuvant chemotherapy in patients with Stage III colon cancer. The CIRCULATE-IDEA trial picks up where the IDEA trial left off, with groups across Japan, the U.S. and Europe collaborating to explore optimal treatment strategies in the era of personalized, tumor-informed MRD testing.

There will be multiple investigational arms in the Japanese CIRCULATE-IDEA trial, including treatment escalation (experimental therapies) in patients who test MRD-positive after surgery, and treatment de-escalation (no chemotherapy at all) in patients who test MRD-negative after surgery. The study’s primary objective is to demonstrate that MRD-negative patients derive no significant clinical benefit from adjuvant chemotherapy and thus may safely avoid it. This outcome, if achieved, would result in a significant change to current medical practice, in which adjuvant chemotherapy is standard for all Stage III patients despite the fact that most patients are cured by surgery alone.

In Japan, CIRCULATE-IDEA is the centerpiece of a new platform study called SCRUM-Japan MONSTAR-SCREEN. If successful, the platform study is expected to support widespread adoption and reimbursement of MRD testing in Japan.

"There are many thousands of colon cancer patients each year who receive unnecessary chemotherapy," said the study’s Principal Investigator, Dr. Takayuki Yoshino of the NCC East, Kashiwa, Japan. "We believe the Signatera technology offers a breakthrough solution to differentiating which patients need further treatment and which do not."

In a published validation study, Signatera detected relapse in patients with Stage II-III colorectal cancer up to 16.5 months earlier (average 8.7 months earlier) than standard diagnostic tools including CT imaging and CEA. Patients who remained MRD-negative throughout the study had significantly reduced risk of relapse, as low as 3%.2

"We are proud to partner with the NCC and the Japanese oncology community on this important trial," said Alexey Aleshin, M.D., M.B.A., Natera’s Senior Medical Director for Oncology. "Helping patients avoid unnecessary treatment is a cornerstone of our vision for Signatera across many cancer types, and we believe this collaboration is an early example of how that story will unfold globally."

About Signatera
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and in 2019 it was granted Breakthrough Device Designation by the FDA. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy; rather it is intended to detect and quantify how much cancer may be left in the body, to detect recurrence earlier, and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers.

Signatera was developed by Natera, Inc. a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

On January 15, 2020 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported meeting the clinical efficacy endpoint of stage 1 of Cohort B in the phase II trial (BGBC008) evaluating bemcentinib in combination with MSD’s Keytruda (pembrolizumab) in previously treated non-small cell lung cancer (NSCLC) patients with confirmed progression on prior immune checkpoint therapy (Press release, BerGenBio, JAN 15, 2020, View Source [SID1234553244]). The trial will advance into the second stage.

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The company reports that the Cohort B, stage 1 efficacy analysis has met the confirmed response of one or more patients therefore continuation to stage two evaluation is planned.

The second stage will enroll a further 16 patients to confirm the safety and clinical efficacy of the combination in NSCLC patients that have confirmed progression on prior immune checkpoint therapy.

Comprehensive exploratory biomarker studies of tumor and blood samples are ongoing to measure of AXL expression and immune modulation. Further results from the trial are expected during 2020 and will be presented at appropriate scientific conferences.

The BGBC008 trial (ClinicalTrials.gov Identifier: NCT03184571) is being sponsored by BerGenBio. MSD, a tradename of Merck & Co., Inc., Kenilworth, New Jersey, USA, will continue to supply Keytruda for use in the study under a collaboration agreement signed in March 2017.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "Reversing resistance to immune checkpoint inhibitors in patients who have relapsed on immunotherapy is a highly desirable alternative to the second-line chemotherapy standard-of-care. We are very excited with these early results in this challenging setting and look forward to expanding the study to confirm these findings and reporting comprehensive translational insight. Furthermore, Cohort C in NSCLC patients having failed 1L chemo-checkpoint inhibitor combination is now recruiting, and top line data should be available in the coming months."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On January 15, 2020 John Theurer Cancer Center at Hackensack University Medical Center in New Jersey reported are participating in a first-in-patients clinical trial assessing VE800, a novel bacteria-containing therapy, in combination with the immunotherapy drug nivolumab (Press release, John Theurer Cancer Center, JAN 15, 2020, View Source [SID1234553243]). Laboratory research has suggested that VE800 may enhance the effectiveness of drugs like nivolumab.

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Nivolumab belongs to a class of drugs called checkpoint inhibitors, which also include pembrolizumab and ipilimumab. Cancer cells use certain proteins to hide from or block the immune system, preventing the elimination of cancer cells by the immune system. The category of drugs called checkpoint inhibitors can take the brakes off the immune response and enable the it to detect and destroy cancer cells. Based on their impressive activity, checkpoint inhibitors have been approved by the FDA and become part of the standard of care for more than 14 different types of cancer, including melanoma, lung cancer, head and neck cancer, bladder cancer, cervical cancer, liver cancer, stomach cancer, breast cancer, and lymphoma.

Though immune blockade has been a game-changer, some patients still do not respond to this treatment or eventually relapse. Efforts to understand why some patients respond more than others have revealed that the answer might be in the microbiome: the trillions of bacteria and other tiny organisms that live in our bodies, the bulk of it being the intestinal flora or "gut microbiome." Growing evidence has shown that the microbiome is an important contributor to human health, playing a role in a number of diseases or conditions including obesity, diabetes, and inflammation, among others. Remarkably, studies have revealed differences in microbiome composition between responders and non-responders to checkpoint inhibitors. This is due to the ability of the microbiome to modulate the immune system and affect the microenvironment of tumors and the immune response.

VE800 is an investigational therapy made up of 11 "friendly" bacterial strains that act in concert to activate cytotoxic CD8+ T cells — immune cells which form the vanguard of the immune system’s response to tumors and a key driver of effective immunotherapies. In preclinical studies, VE800 enhanced the ability of these T cells to get into tumors, promoting the suppression of tumor growth and potentially enhancing survival.

The phase I study, which is being conducted at John Theurer Cancer Center and other centers across the United States, will evaluate the safety and clinical activity of VE800 in combination with nivolumab in patients with advanced or metastatic melanoma, gastric/gastroesophageal junction adenocarcinoma (esophagus/stomach cancer), or a type of colon cancer called microsatellite-stable colorectal cancer. The first results are anticipated in 2021.

"While immunotherapy has revolutionized cancer care, there are still many patients who are not doing as well as we would like with these treatments," explained Martin E. Gutierrez, M.D., Director of Drug Discovery and the Phase I Unit and Chief of Thoracic Oncology at John Theurer Cancer Center. "Modifying the microbiome in combination with immunotherapy is a provocative concept. John Theurer Cancer Center is excited to be part of this pivotal study."