On November 25, 2019 EpicentRx, Inc., a clinical cancer immunotherapy company targeting both sides of the immune system to deliver cancer treatments with minimal toxicity, reported positive results from the Phase 1 G-FORCE trial of RRx-001 as first-line treatment in newly diagnosed glioblastoma (Press release, EpicentRx, NOV 25, 2019, View Source [SID1234551664]). The late-breaking data were presented by Nicholas Butowski, M.D., a principal investigator on the trial and Professor of Neurological Surgery at the University of California San Francisco Weill Institute for Neurosciences, on November 22 at the Society for Neuro-Oncology annual meeting in Phoenix.

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Glioblastoma multiforme (GBM) represents 15-20% of all primary intracranial neoplasm, with death typically occurring within the first 15 months after diagnosis. The median age of diagnosis is 64 years old. Since agents from various drug classes have failed in clinical trials, there is an urgent need for a more effective and less toxic GBM therapy.

RRx-001, EpicentRx’s lead program, is a small molecule immunotherapy targeting the CD47 – SIRPα axis and has been evaluated in multiple clinical studies.

In the G-FORCE trial, 18 patients with histologically verified glioblastoma received RRx-001 plus radiotherapy and temozolomide. After a six-week break, patients in cohorts 1-3 received temozolomide maintenance therapy, while patients in cohorts 4-6 received temozolomide plus RRx-001 maintenance therapy.

RRx-001 combination therapy led to an overall survival (OS) of 21.9 months, compared with historical OS data of 15-20 months. The RRx-001 combo also led to a progression-free survival (PFS) of 13 months, compared with historical PFS data of 6-7 months.

The combination therapy was well tolerated, with no serious adverse events considered related to treatment with RRx-001.

"Patients diagnosed with glioblastoma have poor prognosis and very limited treatment options," said Corey A. Carter, M.D., President & CEO of EpicentRx.

"The results from this Phase 1 G-FORCE study and our ongoing Phase 3 REPLATINUM trial in small cell lung cancer (SCLC) validate RRx-001 as a viable therapy for multiple cancer types. We plan to begin a Phase 0 trial of RRx-001 for GBM in the near future to gain further insight into the mechanism of action in brain tumors before starting Phase 3 studies," added Dr. Carter.

"I am very excited to begin the Phase 0 trial," said Howard Fine, M.D., Director of Neuro-oncology at Weill Cornell Medical Center and principal investigator for the upcoming Phase 0 trial. "This is a high priority project and collaboration for both Weill Cornell and EpicentRx, and an important step in our efforts to bring safe, effective and minimally toxic therapeutics to GBM patients," Dr. Fine said.

RRx-001 has Orphan Drug designation from FDA for SCLC, neuroendocrine cancer and glioblastoma, and from EMA for SCLC.

About RRx-001

RRx-001 is a next generation small molecule immunotherapy being developed by EpicentRx. The therapy targets the CD47 – SIRPα axis and repolarizes tumor associated macrophages (TAMs) and other immunosuppressive cells in the tumor microenvironment to an immunostimulatory phenotype. RRx-001 stimulates the immune system and can be used as monotherapy or in combination with chemotherapy, immunotherapy, radiation and targeted agents, giving the therapy the potential to convert "treatment-resistant" tumors into "treatment-sensitive" tumors. RRx-001 is currently in the Phase 3 REPLATINUM trial for the treatment of third-line and beyond small cell lung cancer (SCLC). RRx-001 is also in the Phase 2 QUADRUPLE THREAT trial for the treatment of SCLC, non-small cell lung cancer, neuroendocrine tumors, ovarian and prostate cancer, and the Phase 2 PREVLAR trial for the prevention of oral mucositis. Clinical studies for the drug have also been conducted for the treatment of colorectal cancer, brain metastases and glioblastoma.

On November 25, 2019 Ferring Pharmaceuticals and Blackstone Life Sciences reported the joint investment of over $570 million USD in nadofaragene firadenovec (rAd-IFN/Syn3), an investigational novel gene therapy in late stage development for patients with high-grade, Bacillus Calmette-Guérin (BCG) unresponsive, non-muscle invasive bladder cancer (NMIBC) (Press release, Ferring, NOV 25, 2019, View Source [SID1234551663]).

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FerGene, a new gene therapy company and Ferring subsidiary, has been created to potentially commercialize nadofaragene firadenovec in the US and to advance the global clinical development. FerGene’s goal is to bring this promising therapy to a patient population which has seen little improvement in their standard of care over the past twenty years. Blackstone will invest $400 million USD and Ferring will invest up to $170 million USD in FerGene. Ferring will also potentially launch and commercialize nadofaragene firadenovec outside of the US.

"Bringing a novel gene therapy to the market requires dedicated focus and capabilities, and FerGene, a Ferring company, will have the resources and team needed to help us potentially bring nadofaragene firadenovec to patients," said Frederik Paulsen, Chairman, Ferring Pharmaceuticals. "Through this new joint financing model between Ferring and Blackstone Life Sciences, we aim to ensure more people with high-grade, BGC unresponsive, non-muscle invasive bladder cancer may benefit from this novel gene therapy if approved."

Nadofaragene firadenovec, currently in late Phase 3 development, has been granted Breakthrough Therapy designation and had its Biologics License Application (BLA) accepted for filing and granted Priority Review by the FDA.

"This innovative partnership with Ferring illustrates the unique value of Blackstone Life Sciences in bringing transformative therapies to market. Our expertise and experience in hands-on clinical development and early commercialization will help further advance this promising therapy for bladder cancer patients in the US and around the world," said Nick Galakatos, Ph.D., Head of Blackstone Life Sciences.

"Through FerGene, Blackstone and Ferring’s goal is to successfully commercialize and further develop this adenovirally mediated interferon alfa-2b gene therapy, a potential breakthrough treatment for high-grade, BCG unresponsive, non-muscle invasive bladder cancer patients," said Paris Panayiotopoulos, Blackstone Life Sciences Managing Director.

Phase 3 clinical trial results will be presented at the Society of Urologic Oncology (SUO) 20th Annual Meeting in Washington, DC on December 5, 2019 by Dr. Colin Dinney, Professor and Chairman of the Department of Urology at the University of Texas MD Anderson Cancer Center (MDACC) and a founder and past president of the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC). Dr Dinney pioneered the development of nadofaragene firadenovec and co-heads the development program alongside Dr. Nigel Parker6 of FKD Therapies Oy (FKD). Upon the potential FDA approval, FerGene will hold the marketing authorization of nadofaragene firadenovec.

FKD is a specialist gene therapy company based in Finland focused on the development and regulatory filing of nadofaragene firadenovec, which has been studied in the Phase 3 trial in 33 centers across the US, in conjunction with the SUO-CTC.

"We are excited to present the Phase 3 data at the upcoming SUO meeting," said Dr. Stephen A. Boorjian, the Coordinating Investigator for the trial and the Carl Rosen Professor of Urology at Mayo Clinic in Rochester, Minnesota. "This trial expands the search for effective alternatives to radical cystectomy for those patients with high-grade, BCG unresponsive, non-muscle invasive bladder cancer, and offers the potential to meaningfully improve future patient care."

About nadofaragene firadenovec

Nadofaragene firadenovec (rAd-IFN/Syn3) is an investigational therapy being developed as a treatment for patients with high-grade, BCG unresponsive, NMIBC. It is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder every three months. The virus enters the cells of the bladder wall, where, it breaks down, releasing the active gene to do its work. The internal gene/DNA machinery of the cells ‘picks up’ the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into multiple interferon microfactories, enhancing the body’s natural defenses against the cancer.

About bladder cancer

Bladder cancer is one of the most frequently occurring cancers, with an estimated 430,000 patients diagnosed worldwide each year, making it the ninth most common cancer worldwide.1,2 In the US, bladder cancer is the sixth most common cancer, with an estimated 699,450 people living with bladder cancer and more than 80,000 new cases diagnosed each year in the US alone. 3 In high-grade NMIBC patients, BCG is the standard treatment, and, although effective, over 60% of these tumors eventually re-occur.2,4 Radical cystectomy (complete removal of the bladder and certain reproductive organs) to prevent the cancer spreading to other organs represents the recommended treatment option in this setting, but may be associated with considerable morbidity.5 As such, the BCG unresponsive population is one of high unmet clinical need, which has been recognized by the FDA Guidance for Industry, February 2018.7

On November 25, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the presentation of data from an expanded, multi-center, prospectively tested patient cohort study supporting clinical use of the DecisionDx-Melanoma test to inform discussions and recommendations regarding sentinel lymph node biopsy (SLNB), as well as data from a separate multi-center prospective outcomes study (Press release, Castle Biosciences, NOV 25, 2019, View Source [SID1234551662]).

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The poster titled, "Identification of melanoma patients with low risk of sentinel lymph node positivity and favorable prognosis using a 31-gene expression profile (GEP) test," was presented during the 16th International Congress of the Society for Melanoma Research in Salt Lake City, Utah.

The data supports the clinical use of DecisionDx-Melanoma test results in combination with clinicopathologic factors to identify patients at low risk of sentinel lymph node (SLN) positivity and that T1-T2 patients identified as low risk by the DecisionDx-Melanoma test had high survival rates. This information can inform patient discussions and recommendations regarding the SLNB surgical procedure in line with national melanoma clinical practice guidelines.

Study Background:

National cancer guidelines recommend the SLNB surgical procedure to assess prognosis of melanoma patients whose tumor features suggest at least a 5% likelihood of sentinel lymph node (SLN) positivity. The guidelines do not recommend the procedure if a patient has a likelihood of SLN positivity of less than 5%.
Among all patients with T1-T2 melanoma (tumor depth of 2 mm or less), only 5-10% have a positive SLNB, with the likelihood of a positive SLN decreasing with age.
The DecisionDx-Melanoma test is a 31-gene expression profile prognostic test for cutaneous melanoma that predicts 5-year risk of metastasis as low risk (Class 1, 1A lowest risk) or high risk (Class 2, 2B highest risk), as well as metastasis to the sentinel lymph node.
The DecisionDx-Melanoma test has been previously validated to identify patients with T1-T2 melanoma with SLN positivity rates below 5%, thus helping guide SLNB discussions and recommendations.
This study was designed to further evaluate the ability of the DecisionDx-Melanoma test to identify T1-T2 melanoma patients with low risk for a positive SLN, using the combination of the previously published cohort with a novel cohort, totaling 1,905 prospectively tested consecutive T1-T2 melanoma patients. The cohort had a median age of 64 years, median Breslow depth of 1.2 millimeters and 13% had ulceration present.
Key Findings

In the expanded, multi-center prospectively tested patient cohort study:

In SLNB-assessed patients 65 years of age or older with T1-T2 tumors and a Class 1A test result, SLN positivity was 2.7%, significantly less than patients with a Class 1B-2A (p<0.01) or Class 2B result (p<0.0001), and below the 5% threshold at which guidelines do not recommend the procedure.
Use of the DecisionDx-Melanoma test to guide SLNB decisions in study patients 65 years of age or older with T1-T2 melanoma, shows that SLNB surgical procedures could be reduced by 58%.
In the multi-center prospective outcomes study:

In a prospective cohort with median follow-up of 3.2 years, Class 1A patients with T1-T2 melanoma, at three years, had overall survival of 99.4%, distant metastasis-free survival of 98.7% and recurrence-free survival of 96.6%, adding further support that this population can safely avoid the SLNB surgical procedure.
"The study data support the clinical use of DecisionDx-Melanoma test results, along with clinical features and patient age, to identify a group of patients who have a likelihood of a positive sentinel lymph node of less than 5%, suggesting they may be able to safely avoid the SLNB procedure," said presenter, David M. Hyams, M.D., Eisenhower Medical Center surgeon, Rancho Mirage, California. "This information can inform patient discussions and recommendations regarding the SLNB surgical procedure in line with national melanoma clinical practice guidelines."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 3,900 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and five prospective risk of recurrence studies including more than 780 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter study cohorts that included more than 2,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

More information about the test and disease can be found at www.SkinMelanoma.com

On November 25, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported an update on the completed tests that are part of the U.S. Food and Drug Administration (FDA) required "release testing" related to the company’s first manufactured batch of its clinical trial product to be used in its planned Phase 2b clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, NOV 25, 2019, View Source [SID1234551661]).

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There are 10 total tests that make up the company’s "release testing." To date, 5 of those 10 tests have been completed and all 5 have passed, including 4 of the 5 tests being conducted by third-party laboratories on the first manufactured batch of PharmaCyte’s clinical trial product.

PharmaCyte’s partner, Austrianova Singapore (Austrianova), is conducting 5 of the tests, which are all related to the "functionality" of the encapsulated cells, while third-party laboratories are conducting the remaining 5 tests, which are all related to the "safety" of the company’s clinical trial product.

Among those successful tests was the "enzymatic activity" test that was performed by Austrianova. The last remaining test being conducted by a third-party laboratory is still in progress and is being conducted in the Netherlands by Eurofins.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said of the release testing, "We continue to be pleased that we’ve completed all of our manufacturing runs successfully and that we have a clinical trial product. Now, we follow that initial news with more good news that all of the release testing from the first successful manufacturing run carried out so far has been completed successfully.

"While the release testing is being conducted, we’re working to finalize the Protocol, the Investigator Brochure, the Pharmacy Manual and the Angiography Guidelines. We are also engaged in a selection process for a vendor to handle our clinical drug supply chain. All of these tasks should be complete by the time we receive the data from all of the release testing being conducted on the first and second manufacturing runs.

"After we receive all of the results from release testing, we will enter the data from those results into our Investigational New Drug application (IND) and then submit an entire package of information and supporting documents to the FDA for our planned Phase 2b clinical trial in LAPC."

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source

On November 25, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that Health Canada has approved the supplemental New Drug Submission that expands the use of ADCETRIS (brentuximab vedotin) in combination with CHP (cyclophosphamide, doxorubicin, prednisone) chemotherapy for the treatment of previously untreated adult patients with systemic anaplastic large cell lymphoma (sALCL), peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumours express CD30 (Press release, Seattle Genetics, NOV 25, 2019, View Source [SID1234551660]). The approval is based on positive results of the phase 3 ECHELON-2 clinical trial that compared ADCETRIS plus CHP to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Health Canada granted a Priority Review Designation for this submission. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL.

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"The Health Canada approval of ADCETRIS (brentuximab vedotin) in combination with CHP chemotherapy in newly diagnosed CD30-expressing peripheral T-cell lymphoma represents the first major advance for Canadian patients with PTCL in decades," said Kerry Savage, M.D., Medical Oncologist at the BC Cancer Agency, Professor of Medicine at the University of British Columbia and investigator on the ECHELON-2 clinical trial. "The approval is based on the ECHELON-2 clinical trial that demonstrated ADCETRIS (brentuximab vedotin) plus CHP regimen was superior for both progression-free survival and all key secondary endpoints, including overall survival, when compared to the standard of care CHOP chemotherapy."

"The current standard of care for initial treatment of peripheral T-cell lymphoma is multi-agent chemotherapy, which results in low complete remission rates and poor progression-free and overall survival. ECHELON-2 is the first randomized trial to demonstrate an overall survival benefit over established standard therapy, making it a meaningful advance in the treatment of these rare lymphomas," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "With this new indication for ADCETRIS, physicians and eligible patients in Canada now have access to this important new regimen for treating frontline CD30-expressing peripheral T-cell lymphoma, another milestone supporting our plans to continue to expand ADCETRIS globally to patients in need."

In May 2019, Health Canada approved the supplemental New Drug Submission that expanded the use of ADCETRIS in combination with AVD (Adriamycin, vinblastine and dacarbazine) chemotherapy in patients with previously untreated Stage IV Hodgkin lymphoma (HL) based on the results of the phase 3 ECHELON-1 clinical trial.

About T-Cell Lymphomas

There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine).

ADCETRIS has received marketing authorization by regulatory authorities in 73 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.