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OncoSec Initiates Registration Directed Clinical Trial, KEYNOTE-695, of ImmunoPulse® IL-12 in Combination with Merck’s KEYTRUDA® (pembrolizumab)

On October 10, 2017 OncoSec Medical Incorporated ("OncoSec" or the "Company") (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported that it has initiated its phase 2b registration directed trial, PISCES/KEYNOTE-695 (Press release, OncoSec Medical, OCT 10, 2017, View Source [SID1234520867]). The PISCES/KEYNOTE-695 study is a global, multicenter phase 2b trial of OncoSec’s investigational therapy, ImmunoPulse IL-12 (intratumoral pIL-12 [tavokinogene telseplasmid or "tavo"] with electroporation), combined with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the US and Canada), in patients with unresectable metastatic melanoma who have progressed or are progressing on an anti-PD-1 therapy.

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"Patients with metastatic melanoma who are progressing or have progressed on anti-PD-1 therapy have limited treatment options. We believe the combination of ImmunoPulse IL-12 and pembrolizumab offers a potentially transformative approach for these patients given the absence of approved therapies," said Punit Dhillon, CEO and President at OncoSec. "The advancement of the PISCES trial marks an important milestone for the Company."

The phase 2b, Simon 2-stage multicenter study of intratumoral tavo with electroporation in combination with intravenous KEYTRUDA will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).

"ImmunoPulse IL-12 and pembrolizumab are immunotherapies designed to modulate the patient’s own immune response to fight cancer," said Sharron Gargosky Ph.D., Chief Clinical and Regulatory Officer at OncoSec. "We are pleased with the progress of the ongoing PISCES trial, which has benefitted from our clinical trial collaboration and supply agreement with Merck."

The collaboration agreement, which was announced in May 2017, is between OncoSec Medical Incorporated and Merck, through a subsidiary. Under the agreement, OncoSec will sponsor and fund the study and Merck will provide KEYTRUDA.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov via NCT03132675.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ImmunoPulse is a registered trademark of OncoSec Medical Incorporated, San Diego, CA, USA.

About Metastatic Melanoma1

Melanoma is a type of skin cancer that begins in skin cells called melanocytes. As the cancer progresses, melanoma becomes more difficult to treat once it spreads beyond the skin, such as the lymphatic system (metastatic disease). Given its occurrence young individuals, the potential years of life lost to melanoma can be higher when compared with other cancers. Although melanoma is a rare form of skin cancer, it accounts for over 75% of skin cancer deaths. The American Cancer Society estimates that approximately 87,000 new melanoma cases and 10,000 deaths from the disease will occur in the United States in 2017. Additionally, the World Health Organization estimates that approximately 132,000 new cases of melanoma are diagnosed around the world every year.

1 American Cancer Society (View Source); World Health Organization (View Source)

About PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study)

PISCES is a global, multicenter phase 2b, open-label trial of intratumoral plasma encoded IL-12 (tavokinogene telseplasmid or "tavo") delivered by electroporation in combination with intravenous pembrolizumab in patients with stage III/IV melanoma who have progressed or are progressing on either pembrolizumab or nivolumab treatment. The Simon 2-stage study of intratumoral tavo plus electroporation in combination with pembrolizumab will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).

Astellas and Seattle Genetics Initiate Pivotal Trial of Enfortumab Vedotin for Patients with Locally Advanced or Metastatic Urothelial Cancer (pdf 203KB)

On October 10, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") and Seattle Genetics Inc., Inc., (NASDAQ: SGEN) reported dosing of the first patient in EV-201, a registrational phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with checkpoint inhibitor (CPI) therapy (Press release, Astellas, OCT 10, 2017, View Source [SID1234520836]). The EV-201 study will assess the antitumor activity and safety of enfortumab vedotin to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations.

"Locally advanced or metastatic urothelial cancers are often aggressive and treatment-resistant. Treatment options are limited for those many patients who do not respond to chemotherapy and checkpoint inhibitors, or CPIs. In addition, there are no FDA-approved therapies for patients who progress following CPI treatment," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Initiation of this pivotal phase 2 trial of enfortumab vedotin is a significant advance toward our goal of providing a new treatment option for patients with locally advanced or metastatic urothelial cancer."

The primary endpoint of the single-arm, open-label trial is confirmed objective response rate (ORR), per independent review. Secondary endpoints include assessments of overall survival, progression free-survival, safety and tolerability. The study will enroll approximately 120 patients at multiple centers globally, and enfortumab vedotin will be administered three of every four weeks for the duration of treatment.

"The initiation of the EV-201 clinical trial demonstrates our continued commitment to patients living with locally advanced or metastatic urothelial cancer," said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. "Our decision to move forward with this registrational trial is based on the results of our ongoing Phase 1 study, and we look forward to future clinical development milestones for enfortumab vedotin."

The companies also plan to initiate a combination trial of enfortumab vedotin with CPI therapy in late 2017.

For more information about the phase 2 pivotal trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Urothelial Cancer

Urothelial cancer is most commonly found in the bladder (90 percent). According to the American Cancer Society, approximately 79,000 people in the U.S. will be diagnosed with bladder cancer during 2017 and almost 17,000 will die from the disease. Outcomes are poor for patients diagnosed with metastatic disease, with a five-year survival rate of five percent.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary, industry-leading linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys (an affiliate of Astellas), which is expressed on many solid tumors. Nectin-4 is highly expressed in urothelial cancers, particularly in bladder cancer. Preclinical data demonstrate that enfortumab vedotin binds to Nectin-4 on cancer cells and releases the cell-killing agent into these target cells upon internalization.

Teva to Report Third Quarter 2017 Financial Results on November 2, 2017

On October 10, 2017 Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) reported that it will release its third quarter 2017 financial results on Thursday, November 2, 2017 at 7:00 a.m. ET(Press release, Teva, OCT 10, 2017, View Source [SID1234520906]).

Teva will host a conference call and live webcast on the same day, at 8:00 a.m. ET to discuss its third quarter 2017 results and overall business environment. A Question & Answer session will follow this discussion.

In order to participate, please dial the following numbers (at least 10 minutes before the scheduled start time): United States 1-866-869-2321; Canada 1-866-766-8269 or International +44(0) 203 0095710; passcode: 91932782. For a list of other international toll-free numbers, click here.

A live webcast of the call will also be available on Teva’s website at: www.ir.tevapharm.com Please log in at least 10 minutes prior to the conference call in order to download the applicable audio software.

Following the conclusion of the call, a replay of the webcast will be available within 24 hours on the Company’s website. The replay can also be accessed until November 30, 2017, 9:00 a.m. ET by calling United States 1-866-247-4222; Canada 1-866-878-9237 or International +44(0) 1452550000; passcode: 91932782.

CEL-SCI GRANTED EUROPEAN PATENT FOR MULTIKINE’S MECHANISM OF ACTION IN MAKING TUMORS ‘VISIBLE’ TO THE IMMUNE SYSTEM

On October 10, 2017 CEL-SCI Corporation (NYSE American: CVM) reported that the European Patent Office has issued a new patent to CEL-SCI for its lead investigational immunotherapy, Multikine* (Leukocyte Interleukin, Injection), which is currently in a pivotal Phase 3 trial for head and neck cancer (Press release, Cel-Sci, OCT 10, 2017, View Source [SID1234520870]). Patent # EP 1 879 618 B1 is titled, “A Method for Modulating HLA Class II Tumor Cell Surface Expression With A Cytokine Mixture” addresses Multikine’s mechanism of action to make tumors more visible to the immune system.

“This is a key patent which along with the other Multikine issued patents addresses how Multikine enables the immune system to recognize and attack the tumor. One way tumor cells evade the immune system is by expressing human leukocyte antigens (HLA) on the tumor cell surface, thus appearing as ‘self’ to the immune cells and therefore the tumor cells are not attacked,” stated Eyal Talor, PhD, CEL-SCI’s Chief Scientific Officer. “It is important to note that the tumors of the Multikine-treated responders in our prior Phase 2 studies had no HLA Class II expressed on the cell surface following Multikine treatment as compared to controls**. This points to Multikine’s ability to modulate HLA expression on the tumor cell surface, thereby allowing the immune system to recognize and attack the tumor.”

Geert Kersten, CEO of CEL-SCI commented, “As we are now nearing the end of our Phase 3 study with Multikine in head and neck cancer, this recently issued European patent is very important. It further fortifies our IP estate, which includes a number of issued patents for Multikine in the US, Europe and other major world markets including Japan and China, where we hope to make Multikine available to patients, upon regulatory and marketing approval.”

** Timar et al, JCO 2005 (a Pathology Study)

Resminostat demonstrates potential to significantly alleviate itching in CTCL patients

On October 10, 2017 4SC AG (4SC, FSE Prime Standard: VSC) reported that it is currently investigating resminostat as maintenance therapy in the pivotal RESMAIN study in advanced-stage cutaneous T-cell lymphoma (CTCL) and this new preclinical data provides a better understanding of the molecular basis of resminostat’s anti-itching potential in patients with CTCL (Press release, 4SC, OCT 10, 2017, View Source [SID1234520869]).

Itching in CTCL
CTCL is a blood cancer that arises from the malignant transformation of T cells – a specialized immune cell – where patients suffer from disfigurement and severe itching. To date, the underlying molecular mechanism of itching in CTCL has not been well understood and established anti-itching drugs such as anti-histamines have proven ineffective in CTCL patients.

Resminostat down-regulates itching-associated molecule in CTCL cell line
“From historical data we know that the messenger molecule IL-31 is produced by malignant T-cell populations in CTCL and high levels of IL-31 correlate with itching. It has also been established that in comparison to other treatment options, inhibitors of histone deacetylases (HDAC) can more effectively reduce itching in these patients,” explained Roland Baumgartner, Ph.D., Chief Scientific Officer of 4SC.

“Resminostat is an HDAC inhibitor that reactivates silenced genes in cancer cells and downregulates excessively active genomic areas. We performed a genome-wide analysis of a CTCL cell line before and after addition of resminostat and found that the expression of IL-31 was significantly reduced after treatment with resminostat. These new data provide an important addition to our understanding of how resminostat can alleviate itching in these patients, and in addition, given that time to symptom worsening is one of the major endpoints in our RESMAIN study, these data support our clinical development plans to advance resminostat to market authorization and to offer a new and effective treatment option to CTCL patients and physicians.”

Poster presentation at the EORTC CLTF Meeting
Matthias Borgmann, Ph.D., Product Manager (Resminostat) of 4SC, will present the scientific details at the EORTC CLTF Meeting | Cutaneous Lymphomas: Insights & Therapeutic Progress 2017 Meeting.
Posters Resminostat’s action in CTCL – hints from a genome-wide study
A multicentre, double blind, randomised, placebo controlled, Phase II trial to evaluate Resminostat for maintenance treatment of patients with advanced stage (Stage IIB IVB) mycosis fungoides (MF) or Sézary Syndrome (SS) that have achieved disease control with systemic therapy – the RESMAIN Study
Time Poster Session, 15 October 2017, 9:00 to 10:15 a.m. (BST)
Location Hilton London Tower Bridge Hotel, United Kingdom
Related articles
13 September 2017, Phase I study of 4SC’s resminostat indicates efficacy in biliary tract cancer
30 May 2017, Resminostat enhances immune cell cancer cell interaction
3 May 2017, Progress update on pivotal RESMAIN study of resminostat in CTCL at 13th Congress of the EADO

About resminostat
Resminostat is orally administered and potentially offers a novel approach for the treatment of a wide variety of cancers, both as monotherapy and in combination therapy with other anti-cancer drugs. Resminostat inhibits tumor growth and proliferation, causes tumor regression, and strengthens the body’s immune response to cancer.
Resminostat has been shown to be well tolerated in several clinical trials. Resminostat is currently being investigated in a Phase II pivotal study in cutaneous T-cell lymphoma (CTCL) by 4SC. A Phase II study in biliary tract cancer is planned by 4SC’s development partner Yakult Honsha in Japan. Amongst others, resminostat has previously been investigated in biliary tract or pancreatic cancer and hepatocellular carcinoma (HCC).

About cutaneous T-cell lymphoma (CTCL)
CTCL is a rare disease with approximately 5,000 patients being newly diagnosed in Europe each year. The disease arises from malignant transformation of T cells, a specialized subgroup of immune cells, primarily affects the skin, but may ultimately involve lymph nodes, blood and visceral organs.

Currently, CTCL is not curable and treatment options for advanced-stage CTCL are limited. Although patients respond to the available treatment options, the duration of response is often short-lived and declines as the severity of the disease increases. The key therapeutic challenge in advanced-stage CTCL is therefore to make remissions more durable, halting disease progression, improving quality of life and prolonging progression free and overall survival.

About the RESMAIN study – Resminostat for maintenance treatment of CTCL
The RESMAIN pivotal study is open for recruitment since November 2016 and is being conducted at more than 50 clinical centers in 11 European countries. It will include 150 patients who suffer from advanced-stage cutaneous T-cell lymphoma (CTCL) and have achieved disease control with systemic therapy. The patients are randomized 1:1 to receive either resminostat or placebo. Patients who experience disease progression – while being on placebo – will be offered resminostat in an open label treatment arm.

The primary goal of the study is to determine whether maintenance treatment with resminostat prolongs progression-free survival and the key secondary objective is to prolong the time to symptom worsening (itching). A comprehensive biomarker program is also included in the study to ensure vital knowledge about the biological background of resminostat treatment and CTCL is acquired. 4SC anticipates top-line data to be available in 2019.