On June 3, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), reported that Ryan Spencer, Senior Vice President, Commercial, and Interim Co-President, will present at the William Blair & Co. Annual Growth Stock Conference on Thursday, June 6, at 9:20 a.m. C.T (Press release, Dynavax Technologies, JUN 3, 2019, View Source [SID1234536850]).

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The presentation will be webcast and may be accessed at the "Events & Presentations" section of the Company’s website at View Source

On June 3, 2019 Astellas Pharma Inc. (TSE: 4503) (President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq: SGEN) reported that data from the first cohort of a pivotal phase 2 clinical trial known as EV-201 demonstrated that the investigational agent enfortumab vedotin rapidly shrank tumors in most patients, resulting in an objective response rate (ORR) of 44 percent (55/125; 95% Confidence Interval (CI): 35.1-53.2) (Press release, Astellas, JUN 3, 2019, View Source [SID1234536797]). Complete responses (CR) were observed in 12 percent of patients (15/125). The median duration of tumor response was 7.6 months (range 0.95-11.3+). This cohort was open to patients with locally advanced or metastatic urothelial cancer who had received previous treatment with a platinum-containing chemotherapy and a PD-1/L1 checkpoint inhibitor. Responses were similar in the subgroups of patients analyzed, including those who had the worst prognosis, such as patients who had three or more previous lines of therapy, patients with liver metastases, and those who had not responded to a PD-1/L1 inhibitor. Treatment-related adverse events that occurred in 40 percent or more of patients were fatigue, alopecia, rash, decreased appetite, taste distortion, and peripheral neuropathy.

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The data will be featured today in the official press program of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and be presented as a Late-Breaking oral presentation (Abstract #LBA4505) and have been submitted for publication in a peer-reviewed journal.

Despite recent advances in treatment, approximately 80 percent of people do not respond to PD-1/L1 inhibitors, which are the standard of care after platinum-containing therapy has failed as an initial treatment for advanced disease.[1],[2],[3] These patients have few treatment options and new therapies are urgently needed.

Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a protein that is highly expressed in urothelial cancers.[4],[5] Based on the results of the EV-201 trial, the companies plan to submit a Biologics License Application (BLA) for enfortumab vedotin to the U.S. Food and Drug Administration (FDA) this year. Based on preliminary results from the phase 1 EV-101 trial, the FDA granted enfortumab vedotin Breakthrough Therapy designation for people with locally advanced or metastatic urothelial cancer whose disease has progressed during or following checkpoint inhibitor therapy.

"Outcomes for patients diagnosed with locally advanced or metastatic urothelial cancer are generally poor, and treatment options after initial chemotherapy and immunotherapy are very limited," said Daniel P. Petrylak, M.D., Professor of Medicine and of Urology, Yale Cancer Center, New Haven. "These data have the potential to change the treatment course of advanced urothelial cancer, and it is gratifying to see these results for patients."

"Even with the recent introduction of new therapies, there remains a need for continued innovation in the treatment of urothelial cancer, and if approved, we hope to bring this potential treatment to physicians and patients as quickly as possible," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

"We are encouraged that enfortumab vedotin is the first novel therapy to demonstrate substantial clinical activity in these difficult-to-treat patients who currently have limited treatment options," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

A global, randomized phase 3 confirmatory clinical trial (EV-301) is ongoing and is intended to support global registrations. Another trial (EV-103) is underway to evaluate enfortumab vedotin in earlier lines of treatment for patients with locally advanced or metastatic urothelial cancer, including in combination with pembrolizumab and/or platinum chemotherapy in newly diagnosed patients as well as patients who progressed from earlier-stage disease.

EV-201 Study Results

Efficacy
In the first cohort of the EV-201 study, 125 patients were treated with enfortumab vedotin. The primary endpoint of confirmed objective response rate (ORR) was 44 percent per blinded independent central review (BICR) [(55/125; 95% CI: 35.1-53.2)]. The overall duration of response (DoR), a key secondary endpoint, was 7.6 months (range 0.95-11.3+).

Most responses occurred within the first cycle of treatment, and were observed across all pre-specified patient subgroups irrespective of lines of therapy, response to prior PD-1/L1 inhibitor, or presence of liver metastases:

Three or more prior therapies: 41 percent ORR (26/63)
Non-responders to PD-1/L1 inhibitors: 41 percent ORR (41/100)
Liver metastases: 38 percent ORR (19/50)
Median overall survival (OS) was 11.7 months (95% CI:9.1-not reached), and the median progression-free survival (PFS) was 5.8 months (95% CI:4.9-7.5).

Safety

The most common treatment-related adverse events (AEs) occurring in more than 40 percent of patients were fatigue (50 percent (62/125)); alopecia (49 percent (61/125)); rash (48 percent (60/125)); decreased appetite (44 percent (55/125)); taste distortion (40 percent (50/125)); and peripheral neuropathy (50 percent (63/125)).
Most peripheral neuropathy (94 percent) and rash (75 percent) were less than or equal to Grade 2 in severity. Hyperglycemia occurred in 11 percent of patients (14/125).
The most common severe AEs (defined as greater than or equal to Grade 3) were: neutropenia – experienced by 8 percent of patients (10/125); anemia in 7 percent of patients (9/125); and fatigue in 6 percent of patients (7/125). One death due to interstitial lung disease occurred outside the safety-reporting period and was confounded by prolonged high-dose steroid use and suspected pneumonia.
About the EV-201 Trial
EV-201 is an ongoing single-arm, pivotal phase 2 clinical trial of enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2). EV-201 continues to enroll patients in cohort 2. In cohort 1, 128 patients were enrolled at multiple centers internationally.[6] The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

More information about enfortumab vedotin clinical trials can be found at clinical trials.gov.

About Urothelial Cancer
Urothelial cancer is the most common type of bladder cancer (90 percent of cases).[7] In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States.[8] Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.

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 linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule that is expressed on many solid tumors, and that has been identified as an ADC target by Astellas.

The safety and efficacy of enfortumab vedotin are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval or become commercially available for the uses being investigated.

On June 3, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, is reported an analyst and investor event today featuring distinguished oncologists Professor Johann de Bono and Dr. Rebecca Kristeleit, to discuss clinical findings and possible next steps for its oral, highly selective Chk1 inhibitor, SRA737 (Press release, Sierra Oncology, JUN 3, 2019, View Source [SID1234536813]).

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On Saturday, June 1st, Sierra reported positive preliminary clinical data from its two first-in-human Phase 1/2 studies of SRA737, as monotherapy and as SRA737+LDG (low dose gemcitabine), at the 2019 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago. Detailed results were issued by press release on June 1st and are available on Sierra’s website at www.sierraoncology.com. Anti-cancer activity was demonstrated across multiple indications and genetic contexts, with SRA737+LDG specifically achieving a notable 30% response rate in anogenital cancer patients, an indication for which the second line metastatic setting represents a significant unmet medical need with no approved therapies and very poor life expectancy. Additionally, subjects whose tumors harbored FA/BRCA gene network mutations displayed favorable outcomes, including an Overall Response Rate = 25% and Disease Control Rate = 81%.

"These positive data indicate that SRA737 is a demonstrably active anti-cancer drug that we believe warrants further development. The initial efficacy and favorable tolerability profile described at ASCO (Free ASCO Whitepaper) also enables several potentially promising opportunities for its development in combination with other therapeutics, in particular with PARP inhibitors and immunotherapy agents where we have previously reported robust preclinical efficacy data," said Dr. Nick Glover, President and CEO of Sierra Oncology. "We also look forward to announcing regulatory clarity for our lead asset momelotinib in the near-term. We have been holding productive discussions with regulators and continue to prepare for a Phase 3 clinical trial intended to potentially support its registration. Given momelotinib is our lead drug candidate and highest priority, we will be exploring options to enable the continued advancement of SRA737 in the context of our emerging pipeline."

SRA737 Analyst & Investor Event
The company is hosting an Analyst and Investor Event on Monday, June 3, 2019, to discuss these clinical findings and potential next steps in the development strategy for SRA737+LDG.

Date and Time: June 3, 2019, 6:00 – 7:00 am CT

Location: History event room, Marriot Marquis Hotel, 2121 S Prairie Ave, Chicago, Illinois.

The event will feature presentations by two distinguished oncologists:

Professor Johann de Bono, Regius Professor of Cancer Research, Head of the Division of Clinical Studies and Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, will discuss the critical role of Chk1 in tumor cell survival during replication stress, as well as describe potential opportunities to combine SRA737 with other therapeutic modalities including PARP inhibitors and immunotherapy agents.
Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Honorary Consultant Medical Oncologist at University College London (UCL) Cancer Institute & UCLH Dept. of Oncology, a leading expert in gynecological malignancies, will discuss her clinical experience with SRA737+LDG, and potential development opportunities for this novel combination in the treatment of anogenital cancers.
Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. An archive of the presentation will be accessible after the event through the Sierra Oncology website.

About SRA737 and SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). Tumors with high levels of replication stress become reliant on Chk1 to mitigate the potentially catastrophic consequences of excess genomic instability.

Intrinsic sources of replication stress can include genetic alterations in tumor suppressors, oncogenes or DNA Damage Repair genes. Tumors harboring defects in these gene classes are hypothesized to have higher levels of intrinsic replication stress due to dysregulated cell cycle control, increased proliferation demands and increased genomic instability. SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine (LDG) acts as a potent extrinsic inducer of replication stress.

Sierra Oncology retains the global commercialization rights to SRA737.

On June 3, 2019 Servier and Taiho Oncology, Inc. a subsidiary of Taiho Pharmaceutical Co., Ltd. (Japan), reported LONSURF (trifluridine/tipiracil, TAS-102) clinical data in metastatic gastric cancer (mGC), metastatic gastroesophageal junction adenocarcinoma (mGEJC) and metastatic colorectal cancer (mCRC) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Servier, JUN 3, 2019, View Source [SID1234536834]).

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Patients over the age of 65 make up 60% of those with gastric cancer, with the average age of diagnosis being 68 years old.1 Therefore it is important to demonstrate the effectiveness of LONSURF for the treatment of gastric cancer for this population. To determine the efficacy and tolerability of LONSURF a subgroup analysis from the global Phase III trial TAGS was conducted. This study demonstrated that the safety and efficacy of LONSURF in patients 65 years and older who have a higher incidence of moderate renal impairment versus the placebo was comparable to the overall population included in TAGS. Additionally there were no reported treatment-related deaths among this sub-population, dose modification was more common but this did not lead to an increase in discontinuation compared to the overall population.2

"We are pleased to present further data from the global Phase III trial TAGS, the subgroup analyses reinforces the clinical benefit and safety profile of LONSURF for those aged over 65 years old with mGC and for patients with mGEJC," said Patrick Therasse, Head of Servier Research and Development Oncology. "Patients with mGC/mGEJC have no standard of care in the EU, and the data supports LONSURF as an effective and tolerable treatment option for those patients with advanced disease."

The abstracts presented at ASCO (Free ASCO Whitepaper) were:

A subgroup analysis from the Phase III TAGS trial in previously treated mGC and mGEJC patients demonstrates safety and efficacy of LONSURF in patients 65 and older who have a higher incidence of moderate renal impairment vs the overall population. (abstract #4037)
A subgroup analysis from the Phase III TAGS trial demonstrates a manageable safety profile and consistent efficacy in patients with previously treated mGEJC. (abstract #4038)
Health-related quality of life (HRQoL) data from the Phase III TAGS trial in previously treated mGC and mGEJC patients shows that treatment with LONSURF is associated with a trend toward a lower risk of QoL deterioration than placebo consistent across all symptoms and functional scales. (abstract #4043)
A pooled safety analysis of patients receiving at least one dose of LONSURF in the two Phase III trials, TAGS and RECOURSE studies demonstrates a consistent safety profile across patients with mGC/mGEJC or mCRC compared with placebo. (abstract #4039)
LONSURF is indicated in the European Union for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapies, anti-VEGF agents, and anti-EGFR agents. Applications for an additional indication in mGC including mGEJC for LONSURF are currently under review by health authorities in Australia, the European Union, Japan and Switzerland.

In February 2019, the U.S. Food and Drug Administration (FDA) approved LONSURF for the treatment of adult patients with metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

#ENDS#

About TAGS

TAGS (TAS-102 Gastric Study) is a Taiho-sponsored, global, randomized, double-blind, placebo controlled, Phase III study evaluating the efficacy and safety of LONSURF in 507 adult patients with previously treated mGC or mGEJC. The primary endpoint was overall survival (OS), and the key secondary endpoints included progression-free survival (PFS), safety and tolerability, as well as quality of life. LONSURF demonstrated statistically significant improvement in OS and PFS compared with placebo. The median OS improved from 3.6 months with placebo to 5.7 months with LONSURF, HR 0.69 (95% confidence interval [CI], 0·56-0·85; P=0.00058).

For more information on TAGS, please visit www.ClinicalTrials.gov (View Source). The ClinicalTrials.gov Identifier is NCT02500043.

About RECOURSE

The RECOURSE trial is a global, randomized, double-blind, placebo-controlled Phase III trial evaluating the efficacy and safety of LONSURF in patients with previously treated mCRC. The trial enrolled 800 patients in North America, Japan, Europe and Australia. Patients were randomized (2:1) to receive LONSURF (35 mg/m2) or placebo, plus BSC, twice daily. The study met its primary and secondary endpoints of OS and PFS versus placebo. The median OS improved from 5.3 months with placebo to 7.1 months with LONSURF, HR 0.68 (95% CI, 0.58 to 0.81; P<0.001).

About Metastatic Gastric Cancer

Gastric cancer, also known as stomach cancer, is a disease in which malignant cells form in the lining of the stomach. It is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and colorectal cancer), with an estimated 780,000 deaths annually.3　

When cancer spreads it is called advanced cancer. Locally advanced cancer is when the cancer has grown outside the organ it started in but hasn’t spread to other parts of the body. When the cancer spreads to other parts of the body, this is called metastatic cancer. In the last two decades, the proportion of patients with gastric cancer who present with metastases has risen to over 40%.4

Standard chemotherapy regimens for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. The addition of trastuzumab to chemotherapy is standard of care for patients with HER2/neu-positive advanced gastric cancer. However, after failure of first- and second-line therapies, there are neither approved nor standard third-line treatments in the EU.

About Metastatic Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide with approximately 1.8 million new diagnoses in 2018. Each year there are over 880,000 deaths making it the second biggest cancer killer worldwide (after lung cancer).5

Those with metastatic disease (where the cancer has spread from the primary site) the average five-year survival is approximately 11%.6 Standard chemotherapy regimens for advanced mCRC include fluoropyrimidines, oxaliplatin, irinotecan or targeted treatments, such as those that target vascular endothelial growth factors (VEGF) or endothelial growth factor receptors (EGFR).

Over the last decade, clinical outcomes for patients with mCRC have improved considerably due to the advent of novel treatment agents, predictive biomarkers, and a more strategic approach to the delivery of systemic therapies. Currently, the median overall survival for patients with mCRC being treated both in phase III trials and in large observational series or registries is 30 months – more than double that of 20 years ago.7,8,9

About LONSURF10

LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation.

In the EU, LONSURF is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

As of May 2019, LONSURF has been approved as a treatment for advanced mCRC in 67 countries and regions. In February 2019, LONSURF has been approved as a treatment for mGC/mGEJC in the United States.

LONSURF was discovered and developed by Taiho Pharmaceutical. In June 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Asia

On June 3, 2019 Iovance Biotherapeutics, Inc presented the corporate presentation (Presentation, Iovance Biotherapeutics, JUN 3, 2019, View Source [SID1234536851]).

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