On July 1, 2021 Foundation Medicine, Inc. reported that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for ALUNBRIG (brigatinib), which is currently FDA-approved for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test (Press release, Foundation Medicine, JUL 1, 2021, View Source [SID1234584555]). FoundationOne CDx, the only FDA-approved tissue-based comprehensive genomic profiling (CGP) test, is now able to detect ALK+ mNSCLC and identify patients who may be appropriate for treatment with ALUNBRIG which is approved as a first-line or later-line therapy.

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Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed globally each year. 1 2 Approximately three to five percent of patients with NSCLC have a rearrangement in the ALK gene.3

"This approval reinforces the importance of comprehensive genomic profiling in patient care and confirms its value in guiding treatment decisions at diagnosis of metastatic non-small cell lung cancer," said Brian Alexander, M.D., M.P.H., chief executive officer at Foundation Medicine. "We’re proud to partner with Takeda to ensure patients with this serious condition have access to this important treatment option."

FoundationOne CDx, which now has 28 companion diagnostic claims, is the first and only FDA-approved tissue-based broad companion diagnostic that is clinically and analytically validated for solid tumors. This latest approval reinforces FoundationOne CDx’s ability to detect ALK rearrangements, which can be missed with alternate testing methods.

"It’s exciting to see continued advancement in personalizing medicine," said Gina Hollenbeck, President of ALK Positive. "As a non-small cell lung cancer patient myself who has experienced brain metastases, I know how important it can be to find the right treatment at the right time, especially in the first line."

Foundation Medicine and Takeda entered into an agreement to develop companion diagnostics for therapies in its late-stage lung portfolio in September 2020.

"We are excited by the approval of FoundationOne CDx as a companion diagnostic for ALUNBRIG, an important milestone in the diagnosis and treatment of people living with ALK+ non-small cell lung cancer," said Dion Warren, head, U.S. Oncology Business Unit, Takeda. "The approval of FoundationOne CDx to inform treatment with ALUNBRIG is the first of three companion diagnostics in development as part of our ongoing partnership between Foundation Medicine and Takeda aimed at addressing the urgent need for broad access to genomic tests, and expanding treatment options for people with lung cancer."

ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target ALK molecular alterations. ALUNBRIG is approved in the U.S., European Union (EU) and Japan as a first-line treatment for patients with ALK+ mNSCLC previously not treated with an ALK inhibitor. ALUNBRIG is also approved in more than 40 countries, including the U.S., Canada and the EU, for the treatment of people living with ALK+ mNSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source

On July 1, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) approved a labeling supplement to the U.S. Prescribing Information for NERLYNX that incorporates the use of NERLYNX dose escalation as evaluated in the Phase II CONTROL Trial and the new 133 count commercial NERLYNX SKU (Press release, Puma Biotechnology, JUL 1, 2021, View Source [SID1234584554]). The new 133 count SKU, i.e., a bottle containing a four-week supply of 133 tablets, is aligned with the use of NERLYNX dose escalation and designed to better support patient needs.

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The CONTROL study was a multicenter, open-label, multi-cohort trial evaluating patients with early stage HER2-positive breast cancer treated with NERLYNX 240 mg daily for up to one year who received loperamide prophylaxis with additional anti-diarrheal treatment as needed (PRN) or NERLYNX dose escalation with loperamide as needed. Patients in the dose escalation cohort received NERLYNX 120 mg daily for Week 1, followed by NERLYNX 160 mg daily for Week 2, followed by NERLYNX 240 mg daily for Week 3 and thereafter for the duration of treatment.

Data from this study showed that dose escalation in the extended adjuvant setting, coupled with PRN Loperamide, led to a greater than 60% reduction in the percentage of patients who experienced Grade 3 diarrhea (40% vs. 13%), a 50% reduction in median cumulative days of Grade 3 diarrhea (5 days vs. 2.5 days) and an approximate 80% reduction in discontinuation rates (17% vs. 3%) when compared to ExteNET, where no dose escalation or antidiarrheal prophylaxis was mandated.

Hope S. Rugo, MD, Professor of Medicine at the University of California San Francisco Comprehensive Cancer Center, said, "The inclusion of dose escalation in the prescribing information is a critical road-map for health care providers and patients as they seek to optimize treatment and reduce therapy-related toxicity in the early breast cancer and metastatic settings."

Alan H. Auerbach, Chief Executive Officer and President of Puma, said, "We believe that utilizing dose escalation has the potential to improve the overall tolerability of NERLYNX and increase the average length of therapy, with the end result benefiting more patients battling breast cancer."

About HER2-Positive Breast Cancer

Up to 20% of patients with breast cancer tumors over-express the HER2 protein (HER2-positive disease) and in the ExteNET study, 57% of patients were found to have tumors that were hormone-receptor positive. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer recurring, up to 25% of patients treated with trastuzumab experience recurrence within 10 years, the majority of which are metastatic recurrences.

On July 1, 2021 Novocure (NASDAQ: NVCR) reported final results from its phase 2 pilot HEPANOVA trial in liver cancer testing the safety and efficacy of Tumor Treating Fields (TTFields) together with sorafenib for the treatment of advanced hepatocellular cancer (Press release, NovoCure, JUL 1, 2021, View Source [SID1234584553]). In 21 evaluable patients, the disease control rate was 76% in a patient population with poor prognosis and limited exposure to study treatments. The objective response rate for the intent-to-treat population was 9.5%. In patients who completed at least 12 weeks of TTFields treatment, the disease control rate was 91% with an objective response rate of 18%. The final HEPANOVA results will be presented at the virtual ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer on July 1.

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The HEPANOVA trial enrolled 27 patients with unresectable hepatocellular cancer. Fourteen of the 27 patients, or 52%, had a Child-Turcotte-Pugh (CTP) score of 7 or 8, representing significant liver dysfunction. Six patients, or 22% of the study population, survived less than 12 weeks. The median sorafenib treatment duration was only nine weeks, a much shorter treatment duration than the referenced historical controls1. The median treatment duration of TTFields was 10 weeks.

"We are very encouraged by the HEPANOVA results, especially in light of the poor prognosis of the study population and low treatment exposure," said Dr. Uri Weinberg, Novocure’s Chief Science Officer. "We intend to initiate a randomized controlled trial as soon as possible and are working with key opinion leaders to finalize a protocol incorporating the evolving treatment landscape in advanced liver cancer. We are particularly interested in the potential to use TTFields together with immunotherapy in this aggressive disease given in vivo data which suggest that using TTFields together with anti-PD-1 therapy results in increased tumor response versus either therapy alone."

The objective response rate reached 9.5% in the 21 evaluable patients, more than double the historical controls. The disease control rate was 76%, a much higher rate than the historical controls of 43% to 52%. For the 11 patients who completed at least 12 weeks of TTFields therapy, the objective response rate was 18%. The disease control rate for patients who completed at least 12 weeks of TTFields therapy was 91%. The objective response rate is defined as the percentage of patients who achieved complete or partial response. The disease control rate includes the percentage of responders plus the patients who achieved stable disease. In the intent-to-treat population, median progression free survival was 5.8 months and median time-to-progression was 8.9 months, higher than the historical, sorafenib alone control for both endpoints. No increase in the toxicity of sorafenib and no device-related serious adverse events were reported.

"Hepatocellular cancer is a particularly aggressive disease," said Professor Anca-Ligia Grosu, Medical Director at the University of Freiburg, and the principal investigator of the HEPANOVA trial. "A clear unmet need remains for safe and effective combination treatments. These data show that Tumor Treating Fields have the potential to extend survival in advanced liver cancer without increasing side effects. I look forward to further exploration of efficacy in a randomized, controlled trial."

About Liver Cancer
Liver cancer is a leading cause of cancer deaths worldwide and is the sixth leading cause of cancer deaths annually in the U.S. The incidence of liver cancer is approximately 42,000 new cases annually in the U.S. The five-year survival rate with existing standards of care is less than 20%.

Hepatocellular carcinoma is the most widespread type of cancer that originates from the liver. Advanced liver cancer has spread either to the lymph nodes or to other organs and because these cancers are widespread, they cannot be treated with surgery. The current common standard treatment for patients with advanced disease and those who progressed on loco-regional therapy is systemic therapy with sorafenib, lenvatinib, or atezolizumab plus bevacizumab.

Use of Tumor Treating Fields for the treatment of liver cancer is investigational only.

About Tumor Treating Fields
Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.

On July 1, 2021 Celsion Corporation (NASDAQ: CLSN), Celsion GmbH, a wholly owned subsidiary of Celsion Corporation, a clinical-stage biotechnology company, reported commencement of enrollment in Oxford University’s Phase I PanDox study with ThermoDox in conjunction with Focused Ultrasound in patients with pancreatic cancer (Press release, Celsion, JUL 1, 2021, View Source [SID1234584552]). ThermoDox is Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin.

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This investigator-led study sponsored by the University of Oxford and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre has now received ethics, MHRA and institutional R&D approval to commence (ClinicalTrials.gov Identifier: NCT04852367). PanDox is being carried out as a multi-disciplinary collaboration between Celsion, the Oxford University Institute of Biomedical Engineering, the Oncology Clinical Trials Office (OCTO) and the Oxford University Hospitals NHS Foundation Trust. Prof. Mark Middleton, MD, Head of the Department of Oncology at the University of Oxford is the chief clinical investigator and Prof. Constantin Coussios, FREng, PhD, Director of the Institute of Biomedical Engineering, is the lead scientific investigator.

The primary endpoint of the two-arm 18-subject PanDox study is enhanced uptake of doxorubicin in pancreatic tumors using ThermoDox and Focused Ultrasound (FUS), compared to systemic delivery of free doxorubicin. ThermoDox, a heat activated liposomal doxorubicin, will be administered intravenously in 12 patients with non-resectable pancreatic ductal adenocarcinoma (PDAC) and locally activated by focused ultrasound-mediated hyperthermia. This will be compared to conventional systemic delivery of doxorubicin without FUS in 6 patients.

Secondary endpoints include:

Comparing radiologically assessed tumor activity and response with ThermoDox and FUS to free drug alone.
Examining the impact on patient symptoms of ThermoDox plus FUS.
Assessing the safety profile of both FUS and ThermoDox.
The PanDox study is expected to be completed by December 2022 and is similar in design to Oxford’s 10-patient TARDOX study, which demonstrated that ThermoDox plus focused ultrasound increased doxorubicin tumor concentrations by up to 10-fold and enhanced nuclear drug uptake in patients with liver tumors. The findings of the TARDOX study are published in Lancet Oncology (Lyon et al., 2018) and Radiology (Gray et al., 2019).

Preclinical studies conducted at the University of Washington and published in the International Journal of Hyperthermia describe similarly compelling results from experiments performed in a murine model of pancreatic cancer. Those studies demonstrated that ThermoDox plus focused ultrasound increased localized concentration and nuclear uptake of doxorubicin 23-fold compared with a 2-fold increase for hyperthermia and free doxorubicin.

Commenting on the PanDox clinical study, Dr. Laura Spiers, lead oncology clinical research fellow on the PanDox study, said, "Pancreatic cancer has a low five-year survival rate of approximately 10% and drug-based treatments remain less effective than in other cancers, in part due to the unique challenges presented by the stroma surrounding pancreatic tumors. Therefore, finding innovative and effective means of delivering high concentrations of anti-cancer agents such as doxorubicin may lead to a breakthrough for this difficult-to-treat cancer."

Dr. Michael Gray, lead biomedical engineering research fellow, added, "Based on the patient-specific treatment planning approaches developed and validated during the TARDOX trial, PanDox will deliver focused ultrasound mild hyperthermia without either MR-based or invasive thermometry. The ultimate goal is to develop a cost-effective and scalable approach that can be rapidly deployed for the benefit of pancreatic cancer patients".

"This Phase 1 study at Oxford University is the first new trial to be performed under the auspices of Celsion’s wholly owned subsidiary Celsion GmbH, which was recently established to manage all current and future investigator-sponsored trials with ThermoDox," said Andreas Voss, M.D., managing director of Celsion GmbH. "We look forward to providing ThermoDox and other support to Professor Coussios as he and his colleagues strive to provide options to pancreatic cancer patients, as well as to other investigators pursuing compelling possibilities with ThermoDox."

On July 1, 2021 Pulse Biosciences, Inc. (Nasdaq: PLSE), a novel bioelectric medicine company commercializing the CellFX System powered by Nano-Pulse Stimulation (NPS) technology, reported that it has entered into a stock purchase agreement with Robert W. Duggan, an experienced life sciences executive and the Company’s Board Chairman, for the purchase of 3,048,780 shares of the Company’s common stock at a price of $16.40 per share, the last reported sale price of the Company’s common stock on June 30, 2021, the immediately preceding trading day (Press release, Pulse Biosciences, JUL 1, 2021, View Source [SID1234584551]). All indebtedness owed by the Company to Mr. Duggan pursuant to the loan agreement between Mr. Duggan and the Company dated as of March 11, 2021, including the principal balance of $41.0 million and accrued and unpaid interest of $0.6 million, will be paid through the cancellation and extinguishment of such indebtedness and the issuance of the common stock shares in the private placement. As part of the private placement, Mr. Duggan will invest an additional $8.4 million as new capital.

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"This capital strengthens our balance sheet and enables greater flexibility to drive our top business priorities, the CellFX System Controlled Launch Program and the ongoing product development and initiatives to expand the clinical applications for NPS technology," said Darrin Uecker, President and CEO of Pulse Biosciences. "We appreciate the continued support and leadership from the Chairman of our Board of Directors. The entire team at Pulse Biosciences is excited and committed to deliver the clinically differentiated benefits of Nano-Pulse Stimulation technology to as many patients as possible, starting in aesthetic dermatology."

Mr. Duggan, who currently owns approximately 46% of the Company’s outstanding common stock, will become the beneficial owner of approximately 51% of the Company’s outstanding common stock after giving effect to the private placement. Accordingly, after the closing of the private placement, the Company will be considered a "controlled" company under applicable Nasdaq Stock Market rules.

No warrants will be provided, or other discounts given, to Mr. Duggan in the private placement, and the private placement is being facilitated directly by the Company. As such, no investment banking or placement fees are being incurred by the Company. The private placement is expected to close on or about July 7, 2021, subject to the satisfaction of customary preclosing conditions.

This announcement is neither an offer to sell nor a solicitation to buy any securities, nor shall there be any offer, solicitation or sale of any securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

The shares of common stock being issued in the private placement have not been registered under the Securities Act of 1933, as amended (the "Act"), or any state securities laws, and unless so registered, may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Act and applicable state laws.