On October 23, 2019 GlaxoSmithKline (LSE/NYSE: GSK) reported that the company has received approval from the U.S. Food and Drug Administration (FDA) for an expanded indication for Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer patients, who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either (Press release, GlaxoSmithKline, OCT 23, 2019, View Source [SID1234542453]):

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A deleterious or suspected deleterious BRCA mutation, or
genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.
Patient selection is based on an FDA-approved companion diagnostic for Zejula.
This represents the first time a PARP inhibitor has been approved for use in patients beyond those with a BRCA-positive (BRCA+) mutation as monotherapy in the late-line treatment setting. Now women with late-line, HRD-positive (HRD+) disease are eligible to be treated with a PARP inhibitor.

Axel Hoos, MD, PhD, SVP Oncology R&D, GSK, said: "This new indication reinforces our commitment to providing treatment options for more women impacted by ovarian cancer, especially those with high unmet needs. We look forward to continuing our clinical development program of Zejula and understanding its full potential as a treatment for people living with ovarian cancer."

This new indication is based on the QUADRA study, a Phase 2, multi-center, open-label, single-arm clinical study representing a real world, difficult-to-treat patient population with high unmet needs. QUADRA is the largest clinical trial of a PARP inhibitor in women who received three or more treatments for advanced ovarian cancer. The trial enrolled a broad patient population including women with BRCA+ platinum-sensitive, resistant and refractory disease as well as women with HRD+ platinum-sensitive disease.

Clinically meaningful and durable benefit was demonstrated in the FDA-indicated patient population with an objective response rate (ORR) of 24% (95% CI, 16–34). A median duration of response (mDOR) of 8.3 months (95% CI, 6.5–not estimable) was observed.

Additional analyses were conducted in various sub populations where efficacy of Zejula was also demonstrated for patients with tBRCA and GIS; defined as deleterious or suspected deleterious somatic or germline BRCA mutation and genomic instability score (GIS ≥42) as identified with Myriad’s myChoice companion diagnostic test, respectively:

tBRCA+ platinum-sensitive disease, ORR of 39% (95% CI, 17,64);
tBRCA+ platinum-resistant disease, ORR of 29% (95% CI, 11,52);
tBRCA+ platinum-refractory disease, ORR of 19% (95% CI, 4,46); or
non-BRCA mut, GIS-positive, platinum-sensitive disease, ORR of 20% (95% CI, 8,37).
The safety profile was consistent with that seen in the Phase 3 NOVA trial in the recurrent maintenance population. Most common grade ≥3 adverse reactions reported in ≥10% of patients in the QUADRA study included thrombocytopenia (28%), anemia (27%), neutropenia (13%) and nausea (10%).

Dr. Kathleen Moore, Lead Investigator of the QUADRA study; Director, Oklahoma TSET Phase 1 Program; Associate Professor, Section of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma, said: "Ovarian cancer has a high rate of recurrence, so there is a real need for therapies for women whose cancer has progressed through multiple lines of treatment and who have few or no options left. It’s meaningful to see that Zejula has been approved as a late-line treatment for women including those with and without BRCA mutations."

Ovarian cancer affects nearly 222,000 women in the U.S., and approximately 85% of women with advanced ovarian cancer will see the disease return. With each recurrence, the time a woman may spend without her cancer progressing until the next recurrence gets shorter. Currently, there are few effective options available for treatment of platinum-resistant/refractory advanced ovarian cancer or HRD+ ovarian cancer in the late-line setting. Zejula received initial FDA approval in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. It is the only oral, once-daily PARP inhibitor.

About QUADRA
QUADRA is a large multi-center, open-label, single-arm, Phase 2 registrational study that evaluated the safety and activity of niraparib in adult patients with relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were treated with three or more previous chemotherapy regimens. Four hundred and sixty-three patients were enrolled and received oral niraparib at a starting dose of 300 mg once daily. Treatment was continued until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with HRD+ tumors, including patients with BRCA and without BRCA mutations, sensitive to their last platinum-based therapy. Additional objectives of the study were to evaluate the efficacy of niraparib in the broad late-line ovarian cancer population overall, and in subgroups defined by clinical and molecular biomarkers, such as platinum-sensitivity and BRCA+ and HRD status.

The Myriad myChoice companion diagnostic test was utilized during this clinical trial and has been approved by the FDA as the companion diagnostic test to determine HRD+ status as either tBRCA and/or a genomic instability score (GIS ≥42). GIS is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST).

Information about Myriad myChoice companion diagnostic is available at Myriad.com.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the U.S. Ovarian cancer is the fifth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the front-line, approximately 85% of patients will experience disease recurrence. Once the disease recurs, its considered incurable with time to each future recurrence getting shorter. Late-line treatment options for women with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10% when treated with chemotherapy.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development program by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial as monotherapy maintenance treatment in patients with first-line ovarian cancer (PRIMA), data from this study were recently presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper), a Phase 3 study as a first-line triplet maintenance treatment in ovarian cancer (FIRST), and a Phase 2 study of niraparib combined with bevacizumab maintenance treatment in advanced ovarian cancer (OVARIO).

Several combination studies are also underway, including trials of niraparib plus pembrolizumab in metastatic, triple-negative breast cancer and advanced, platinum-resistant ovarian cancer (TOPACIO). Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

Important Safety Information

Zejula may cause serious side effects, including:

Bone marrow problems called Myelodysplastic Syndrome (MDS) or a type of blood cancer called Acute Myeloid Leukemia (AML). Some people who have ovarian cancer and who have received previous treatment with chemotherapy or certain other medicines for their cancer have developed MDS or AML during treatment with Zejula. MDS or AML may lead to death.

Symptoms of low blood cell counts (low red blood cells, low white blood cells, and low platelets) are common during treatment with Zejula. They can be a sign of serious bone marrow problems, including MDS or AML. These symptoms may include the following:

Weakness
Feeling tired
Weight loss
Frequent infections
Fever
Shortness of breath
Blood in urine or stool
Bruising or bleeding more easily
Uncommonly, fever associated with low white blood cells is observed during treatment with Zejula.

Your doctor will do blood tests to check your blood cell counts before treatment with Zejula. You will be tested weekly for the first month of treatment with Zejula, monthly for the next 11 months of treatment, and from time to time afterward.

High blood pressure is common during treatment with Zejula, and it can become serious. Your doctor will check your blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and as needed thereafter during your treatment with Zejula.

Before starting to take Zejula, tell your doctor about all of your medical conditions, including if you:

Have heart problems
Have high blood pressure
Are pregnant or plan to become pregnant. Zejula may harm an unborn baby and may cause loss of pregnancy (miscarriage)
If you are able to become pregnant, you should use effective birth control (contraception) during treatment with Zejula and for 6 months after taking the last dose of Zejula
If you are able to become pregnant, your doctor may perform a pregnancy test before you start treatment with Zejula
You should tell your doctor right away if you become pregnant
Are breastfeeding or plan to breastfeed
Zejula may harm your baby. You should not breastfeed your baby during treatment with Zejula and for 1 month after taking the last dose of Zejula
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Zejula include the following:

Heart not beating regularly
Nausea
Constipation
Vomiting
Pain in the stomach area
Mouth sores
Diarrhea
Indigestion or heartburn
Dry mouth
Tiredness
Loss of appetite
Urinary tract infection
Shortness of breath
Cough
Rash
Changes in liver function or other blood tests
Pain in your joints, muscles, and back
Headache
Dizziness
Change in the way food tastes
Trouble sleeping
Anxiety
Sore throat
Changes in the amount or color of your urine
If you have certain side effects, then your doctor may change your dose of Zejula, temporarily stop, or permanently stop treatment with Zejula.

These are not all the possible side effects of Zejula. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For full prescribing information visit www.zejula.com/prescribing-information.

myChoice companion diagnostic is a registered trademark of Myriad.

About GSK Oncology
GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On October 23, 2019 The Board of Directors of McKesson Corporation (NYSE:MCK) reported a regular dividend of 41 cents per share of common stock (Press release, McKesson, OCT 23, 2019, View Source [SID1234542452]). The dividend will be payable on January 2, 2020, to stockholders of record on December 2, 2019.

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On October 23, 2019 Cleveland Diagnostics, Inc., a clinical-stage company focused on developing next-generation diagnostic tests for the detection of cancers, reported that its chief medical officer, Mark Stovsky, MD, participated in an Impact Session at the 2019 Medical Innovation Summit organized by Cleveland Clinic (Press release, Cleveland Diagnostics, OCT 23, 2019, View Source [SID1234542451]).

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The Medical Innovation Summit, which is celebrating its 17th year, is covering a wide range of topics including artificial intelligence, new drug discovery, advanced diagnostics development, and the personalization of healthcare. Clinicians, strategists, venture capital groups and other ground-breakers joined renowned clinical experts to discuss, disrupt and deal head-on with issues confronting today’s healthcare ecosystem.

During the Impact Session entitled "Early Detection: A Snag in the System," Dr. Stovsky, CMO of Cleveland Diagnostics and urologist at the Cleveland Clinic, joined other leading industry and government experts to discuss current challenges and opportunities in early detection in cancer. Other topics included early diagnosis of untreatable diseases and the subsequent lack of protocol to move forward.

"We are indeed honored to have Dr. Stovsky join a distinguished panel of speakers on cancer early detection at this meeting," said Arnon Chait, PhD, CEO of Cleveland Diagnostics. "The discussion was both timely and enlightening, and it is clear that some of the leading players in the space are finally beginning to refocus resources on early cancer detection as perhaps the only viable long-term and cost-effective solution to curable approaches in cancer."

Cleveland Diagnostics was recently awarded Breakthrough Device Designation by FDA, which allows Cleveland Diagnostics to work more closely and frequently with FDA to expedite the review of its prostate cancer assay, IsoPSA. Two recent multicenter clinical trials, in which the diagnostic accuracy of IsoPSA was compared to that of traditional prostate-specific antigen (PSA), suggested that IsoPSA has superior diagnostic accuracy in detecting high-grade prostate cancer. Cleveland Diagnostics has a pipeline of simple, cancer-specific and highly cost effective cancer blood tests using the same proprietary core technology.

"The traditional approach to early detection strategies for prostate cancer based on standard serum PSA testing is limited by relatively poor diagnostic accuracy and predictive value. We believe the IsoPSA assay will fill a major gap in this space by providing clinicians with a tool that has improved diagnostic accuracy – particularly for the detection of high grade, clinically actionable prostate cancer," said Dr. Stovsky. "I am thrilled to have had the opportunity to join industry and government leaders, such as Grail, Intel, and NCI, to discuss innovative ways to develop more effective approaches to cancer early detection that will improve the lives of patients worldwide. While we believe that the IsoPSA assay will improve early detection strategies for prostate cancer, we also look forward to exploring ways to work together to design a clinically superior, cost effective early detection paradigm, which might combine virtual screening, protein biomarker testing — such as IsoPSA — and DNA liquid biopsy as a comprehensive approach to this challenging clinical problem."

On October 23, 2019 PharmaMar Group (MSE:PHM) reported total revenues of €62.5 million for 2019 up to September 30th, compared to €88.7 million in the same period last year (Press release, PharmaMar, OCT 23, 2019, View Source [SID1234542450]). The variation in revenues between the first nine months of 2019 and 2018 is due to the difference in revenues from license agreements. In 2018, more than €24 million in revenues from different license agreements were recorded. Some of these agreements may lead to new future revenues, but they have not yet reached the milestones that will lead to them.

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Yondelis’ cumulative sales up to September 30th were €54 million, compared to €57 million in the same period last year.

In relation to the Group’s operating expenses, during the first nine months of the year these decreased in practically all items. In R&D, total expenditure up to September 30th was €41 million, which represents a 27% reduction in expenditure compared to the same period last year. This cost reduction is mainly due to the oncology area. Last year, in addition to the ATLANTIS Phase III trial with lurbinectedin for the treatment of Small Cell Lung Cancer (SCLC), there were other open and active clinical trials that have not been active during the first nine months of 2019, although they remain open until they can be definitively concluded.

In relation to the clinical trials with lurbinectedin, it is important to point out that on August 19th it was announced that the Company will file lurbinectedin’s NDA for the treatment of relapsed Small Cell Lung Cancer (SCLC) in the United States under the "accelerated approval" program during the last quarter of this year. This would open up the possibility that the FDA could approve lurbinectedin in the U.S. for the treatment of SCLC within the next year.

Up to September 30th 2019, the Group has recorded a net attributable result of €- 26.9 million.

Finally, at the end of the first nine months of this year, PharmaMar Group recorded total cash and cash equivalents of €27 million and reduced its net debt to €57.8 million, compared to €65.6 million at the beginning of the year.

On October 23, 2019 Oncotelic Inc. ("Oncotelic"), a wholly owned subsidiary of Mateon Therapeutics Inc. (OTCQB:MATN) dedicated to the development of innovative treatments for cancer, reported the publication of a peer-reviewed research article authored by Fatih Uckun MD PhD and his colleagues at Oncotelic in the Journal of Clinical Research in Pediatrics (View Source) (Press release, Oncotelic, OCT 23, 2019, View Source [SID1234542449]). The article titled "In silico Molecular Target Validation Demonstrates Transforming Growth Factor Beta 2 is Strongly Expressed in Pediatric Diffuse Intrinsic Pontine Glioma and Glioblastoma Multiforme" demonstrates the therapeutic potential of Mateon’s first-in-class RNA therapeutic OT101 for the treatment of diffuse intrinsic pontine glioma (DIPG) and pediatric glioblastoma multiforme (GBM).

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Citation Reference: Uckun FM, Trieu V, Hwang L, Qazi S. In silico Molecular Target Validation Demonstrates Transforming Growth Factor Beta 2 is Strongly Expressed in Pediatric Diffuse Intrinsic Pontine Glioma and Glioblastoma Multiforme. Clin Res Pediatr 2019;2(1):1-10.

"Our research has revealed that the TGF beta2 gene product, which is the molecular target for OT101/Trabedersen, may serve as a target for immunotherapy in pediatric high-grade gliomas, especially DIPG. These in silico target validation data extend the promising clinical data on the therapeutic activity of OT101 in adults and young adults and further demonstrate the potential of OT101 as a promising drug candidate in the treatment of pediatric DIPG, an orphan disease with a low survival rate and no established or effective standard of care," explained Fatih Uckun, MD, PhD, the Chief Medical Officer of Mateon. "The durable objective responses achieved in adult patients with recurrent/refractory high-grade gliomas after treatment with our lead anti-TGF beta2 compound OT-101 contribute to our optimism that new treatment strategies leveraging OT101 may favorably change the therapeutic landscape for difficult-to-treat brain tumors with a very poor prognosis, including pediatric GBM and DIPG," Dr. Uckun explained. Last month, US Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation for OT101/Trabedersen for the treatment of diffuse intrinsic pontine glioma (DIPG) as a drug for a "rare pediatric disease," as defined in section 529(a)(3) of the Federal Food, Drug, and Cosmetic Act.

OT101, a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGF-beta 2, is Oncotelic’s lead anti-brain tumor drug candidate. In a completed Phase 2 clinical study, OT-101 exhibited clinically meaningful single-agent activity and induced durable complete and partial responses in recurrent and refractory adult high-grade glioma patients, including adults with GBM. DIPG, an orphan disease with a low survival rate and no established or effective standard of care. Despite numerous clinical trials of chemotherapeutic agents, immuno-oncology drugs and specific targeted therapies, no significant progress has been made in the treatment of DIPG and the prognosis remains dismal, with a mean OS of 9–12 months from the time of diagnosis, a median survival time of approximately 10 months, and a two-year OS rate of less than 10 percent. Five-year survival is less than 3 percent, and many long-term survivors have evidence of moderate or severe cognitive impairment, likely as a consequence of radiation therapy. Chemotherapy does not have an established role in the management of patients with DIPG. Furthermore, there is no standard treatment for progressive DIPG after the failure of radiation therapy and no salvage regimen has been shown to extend survival. Therefore, there is an urgent need for therapeutic innovations for treatment of DIPG, as reflected by multiple treatment modalities being evaluated in early neuro-oncology clinical trials. Further development of OT-101 may offer renewed hope for salvage therapy of pediatric DIPG patients who have this rare and fatal disease.

"As we move Trabedersen through its clinical development for Pediatric Diffuse Intrinsic Pontine Glioma and Glioblastoma Multiforme, we are moving CA4P forward along the same path as potential treatment for Pediatric Unresectable or Metastatic Melanoma- a rare and difficult to treat pediatric skin cancer, " said Dr. Vuong Trieu, Chief Executive Officer of Mateon "From the corporate side we are moving forward with activities to uplist Mateon. Looking forward to updating our shareholders on the coming quarter."