1stOncology™: Cancer Intelligence Service – Page 14631 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

ERYTECH Confirms Strategic Focus of Eryaspase on Solid Tumors and Ceases Development in Acute Lymphoblastic Leukemia

On June 24, 2018 ERYTECH Pharma (Euronext:ERYP) (Nasdaq:ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that it will focus its development efforts for its product candidate eryaspase on the potential treatment of selected solid tumor indications (Press release, ERYtech Pharma, JUN 24, 2018, View Source;p=RssLanding&cat=news&id=2355698 [SID1234527450]). The company also announced that it plans to cease its development program for eryaspase in acute lymphoblastic leukemia (ALL), including the withdrawal of its previously submitted MAA for eryaspase for the treatment of relapsed and refractory ALL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

In 2017, ERYTECH announced positive results from a Phase 2b clinical trial of eryaspase combined with chemotherapy in patients suffering from second-line metastatic pancreatic cancer, as well as the intended launch of a pivotal Phase 3 clinical trial in this indication. Set-up activities are on track and the Phase 3 trial is expected to begin enrollment in the third quarter of 2018. ERYTECH now confirms that it intends to sponsor a Phase 2 proof-of-concept clinical trial of eryaspase later this year in first-line pancreatic cancer, with enrollment expected to commence in the first half of 2019.

In 2018, following the positive results in second-line metastatic pancreatic cancer, ERYTECH also evaluated other potential solid tumor indications and selected metastatic triple-negative breast cancer (TNBC) as the next indication for which to pursue clinical development of eryaspase. ERYTECH is preparing for a Phase 2 proof-of-concept clinical trial in this indication, with the first patient expected to be enrolled in the fourth quarter of 2018. ERYTECH is also evaluating development options in other pancreatic cancer settings and in additional solid tumor indications with high unmet medical need.

In order to ensure adequate supply of eryaspase for its planned clinical trials, as well as the potential commercialization of eryaspase, if approved, the Company is constructing a large-scale manufacturing facility in the United States (Princeton, New Jersey) and is also expanding its manufacturing capacity in Lyon, France. ERYTECH expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Despite having observed favorable efficacy results and safety profile in multiple clinical trials of eryaspase in patients with ALL, ERYTECH now believes, based on recent feedback from the regulatory agencies in Europe and the United States, that significant additional investment would be required in order to seek regulatory approval of eryaspase for the treatment of ALL. In the context of the rapidly changing and increasingly competitive landscape with newly-approved treatment options for ALL, the regulatory requirements and what ERYTECH observes to be a limited market opportunity for eryaspase in ALL, ERYTECH has elected to cease further clinical development efforts in ALL and to withdraw its European MAA. The resources that will become available as a result of this strategic decision will be allocated to what ERYTECH estimates is a significantly larger unmet medical needs and market opportunity for the potential treatment of solid tumors.

ERYTECH’s preclinical development efforts are not affected by this strategic decision. The next product candidate, erymethionase, methionine-g-lyase encapsulated in red blood cells, and the ERYMMUNE (immuno-therapy) research program are also targeting solid tumor indications. ERYTECH intends to initiate a Phase 1 clinical trial of erymethionase later this year, with enrollment expected to commence in the first half of 2019.

Conference Call Details

ERYTECH management will hold a conference call on Monday, June 25, 2018 at 02:30pm CET / 08:30am EDT. Gil Beyen, Chairman and CEO, Eric Soyer, CFO and COO and Iman El-Hariry, CMO will be available for a Q&A session.

Array BioPharma Announces a 62% Observed Overall Survival at One Year from the Phase 3 BEACON CRC Safety Lead-In of the Combination of Encorafenib, Binimetinib and Cetuximab in BRAF-Mutant CRC at the ESMO 20th World Congress on Gastrointestinal Cancer

On June 23, 2018 Array BioPharma Inc. (NASDAQ: ARRY) reported updated safety and efficacy results, including OS, from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of encorafenib, a BRAF inhibitor, binimetinib, a MEK inhibitor and cetuximab, an anti-EGFR antibody, in patients with BRAFV600E-mutant metastatic colorectal cancer (CRC) (Press release, Array BioPharma, JUN 23, 2018, View Source [SID1234527439]). The results showed that, at the time of analysis, the OS data were fully mature through 12.6 months and that the median OS had not yet been reached. The one-year overall survival rate for this cohort was 62%. These data were presented in an oral presentation on Saturday, June 23, at the ESMO (Free ESMO Whitepaper) 20thWorld Congress on Gastrointestinal Cancer in Barcelona, Spain.

The median progression-free survival (mPFS) for patients treated with the triplet was 8 months [95% CI 5.6-9.3] and is similar between patients receiving one prior line of therapy and patients receiving two prior lines of therapy. The confirmed overall response rate (ORR) was 48% and among the 17 patients who received only one prior line of therapy the ORR was 62%.

"The results of the BEACON CRC safety lead-in demonstrate substantial improvements in efficacy outcomes when compared to current approved standard of care benchmarks in patients with BRAF-mutant metastatic CRC. The median progression-free survival of 8 months is a meaningful improvement compared to the benchmark of about 2 months, and the overall survival of 62% at 12 months is very promising given that with current approved standards of care, half of patients will succumb to their disease within 4 to 6 months," said Axel Grothey, M.D., Division of Hematology/Oncology, Mayo Clinic. "These data underscore the potential of this triplet combination to benefit patients with BRAFV600E-mutant metastatic CRC, who, despite their poor prognosis, currently have limited effective treatment options."

The triple combination was generally well-tolerated with no unexpected toxicities. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).

The presentation also referenced updated, mature Phase 2 results for the doublet of encorafenib and cetuximab that showed a mOS of 9.3 months, mPFS of 4.2 months and an ORR of 24%. The data cutoff for that analysis was January 2018 with the last patient enrolled in April of 2015; a detailed presentation of these data will occur at a future medical congress.

Enrollment in the randomized portion of the BEACON CRC trial is ongoing. Patients interested in participating in this trial may talk to their doctor to have their tumor tested for the BRAF mutation for eligibility to enroll in this new and important trial. Further details on the trial are available at clinicaltrials.gov (NCT02928224).

A PDF of the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer presentation will be available on Array’s website.

Array will host an encore webcast presentation of the BEACON CRC safety lead-in data.

Encore Investor Webcast:

Presenter:

Axel Grothey, M.D., Division of Hematology/Oncology, Mayo Clinic

Date:

Saturday, June 23

Time:

4:30 pm CET (10:30 am ET)

Toll-Free:

(844) 464-3927

Toll:

(765) 507-2598

Pass Code:

8588348

eidos therapeutics announces closing of initial public offering and exercise in full of the underwriters’ option to purchase additional shares

On June 22, 2018 Eidos Therapeutics, Inc. (Nasdaq: EIDX), a clinical stage biopharmaceutical company focused on addressing the large and growing unmet need in diseases caused by transthyretin (TTR) amyloidosis (ATTR), reported the closing of its initial public offering of 7,187,500 shares of common stock, including the exercise in full of the underwriters’ option to purchase 937,500 additional shares of common stock, at a public offering price of $17.00 per share (Press release, Eidos Therapeutics, JUN 22, 2018, View Source [SID1234576276]). The aggregate gross proceeds to Eidos from the offering were approximately

$122.2 million, before deducting underwriting discounts and other offering expenses. All of the shares in the offering were offered by Eidos. Eidos’ common stock is listed on The NASDAQ Global Select Market under the ticker symbol "EIDX."

J.P. Morgan Securities LLC and BofA Merrill Lynch acted as joint book-running managers for the offering. Barclays Capital Inc. also participated as a joint book-running manager.

The shares were offered by Eidos pursuant to a registration statement that was declared effective by the Securities and Exchange Commission ("SEC") on June 19, 2018. A prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov.

This offering was made only by means of a prospectus. Copies of the final prospectus relating to this offering can be obtained from (1) J.P. Morgan Securities LLC, Attention: c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (866) 803-9204, or by emailing [email protected]; (2) BofA Merrill Lynch, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by emailing [email protected]; and (3) Barclays Capital Inc., c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (888) 603-5847, or by emailing [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Alexo Therapeutics Changes Name to ALX Oncology

On June 22, 2018 Alexo Therapeutics, a clinical-stage immuno-oncology company developing therapies to block the CD47 myeloid checkpoint mechanism, reported the change of the Company’s name to ALX Oncology (Press release, Alexo Therapeutics, JUN 22, 2018, View Source [SID1234527433]). The new name and logo will differentiate ALX Oncology (ALX) from other companies in the field as the Company advances its clinical programs.

"Our new name further identifies us as an oncology drug developer and distinguishes us from other companies in this sector," said Jaume Pons, Ph.D., ALX Oncology’s President and Chief Executive Officer.

ALX Oncology is developing ALX148, a high affinity CD47 blocker currently in clinical development (NCT03013218). Preliminary results from the Phase 1 trial were recently presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. "Our study results show that ALX148 is generally well tolerated as a single agent and in combination with pembrolizumab, trastuzumab, or rituximab in patients with advanced solid tumors and non-Hodgkin lymphoma," said Sophia Randolph, M.D., Ph.D., ALX Oncology’s Chief Medical Officer. "We look forward to reporting the results of ALX148 combinations in expanded patient populations at upcoming conferences."

About ALX148
ALX148 is a fusion protein comprised of an engineered high affinity CD47 binding domain of SIRPα linked to an inactive Fc region of human immunoglobulin. ALX148 potently and specifically binds CD47 and blocks its interaction with SIRPα, thus inhibiting a key myeloid immune checkpoint mechanism exploited by cancer cells. In preclinical studies, ALX148 bridges innate and adaptive immunity to enhance anti-tumor response in combination with targeted anti-cancer antibodies and checkpoint inhibitors with no adverse effect on CD47-expressing normal blood cells. ALX148 is currently being investigated in a Phase 1 study in combination with checkpoint inhibitors and targeted anti-cancer antibodies (NCT03013218).

Large-Scale European Review Suggests Disparity in Symptom Recognition and Standardized Treatment for Metastatic Adenocarcinoma of the Pancreas

On June 22, 2018 Shire plc (LSE: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on rare diseases, reported that results from a retrospective review of more than 2,500 patient records with metastatic adenocarcinoma of the pancreas (mPAC) from nine countries (Press release, Shire, JUN 22, 2018, View Source [SID1234527429]). The results – presented on 20 June at the 20th ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2018 (ESMO-GI) in Barcelona – showed variation across Europe in the symptoms reported at initial diagnosis, and in treatment decisions made in the first-line and second-line metastatic settings. The research suggests that enhanced recognition of symptoms and a standardized treatment approach, especially in the second-line setting, may help improve diagnosis, patient care and outcomes.1,2,3

"Pancreatic adenocarcinoma is typically diagnosed late in the course of the disease, when outcomes are generally poor," said Floris de Jong, Ph.D., Global Medical Franchise Lead Solid Tumors at Shire Pharmaceuticals. "These analyses from patient records and NAPOLI-1 collectively provide important new insights for the diagnosis and treatment of patients with this difficult-to-treat cancer. Specifically, the results of the retrospective review indicate that enhanced awareness of, and attention to symptoms both by health care providers and the public at large may help improve mPAC diagnosis, care and outcomes

Researchers also presented new data from four subgroups of the global phase III NAPOLI-1 study in an oral session4. These subgroups included: the presence of metabolism and nutrition disorders at baseline, including diabetes mellitus and decreased appetite; the location of the primary tumor site; the presence of a biliary stent at baseline and response to prior therapy.5,6,7,8

The search for innovative new therapies in pancreatic cancer remains a serious unmet need. Relatively little progress has been made in preventing, detecting and treating the disease relative to other leading cancer killers, and survival rates for pancreatic cancer remain one of the lowest among other types of cancer.9

"While first-line treatments are approved for patients with pancreatic adenocarcinoma, disease progression after initial therapy is inevitable and patients with this disease have a poor prognosis and low survival rate,"9,10 said Teresa Macarulla Mercadé, M.D., Ph.D., Clinical Investigator, Gastrointestinal Tumor Program, Vall d’Hebrón Institute of Oncology, Barcelona. "To further our understanding of the use of nal-IRI in the treatment of mPDAC, we conducted four separate NAPOLI-1 subgroup analyses investigating the effect of selected baseline parameters. These analyses demonstrated that a consistent treatment benefit was observed in patients treated with nal-IRI in combination with 5-FU/LV across the subgroups tested."

The full list of Shire abstracts presented at the 20th ESMO (Free ESMO Whitepaper)-GI in Barcelona includes:

Geographic variation in systemic treatment of metastatic pancreatic adenocarcinoma (mPAC) patients in real world across Europe2
O-002 (oral presentation)
Selected subgroup analyses of liposomal irinotecan (nal-IRI) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the global NAPOLI-1 phase III trial4
O-004
Baseline characteristics and second-line treatment for metastatic pancreatic adenocarcinoma (mPAC) patients receiving first-line FOLFIRINOX, gemcitabine+nabpaclitaxel or gemcitabine-monotherapy in routine clinical practice across Europe3
PD-004 (poster presentation)
Prognostic effect of primary tumor location in the NAPOLI-1 phase III study in metastatic pancreatic ductal adenocarcinoma (mPDAC)6
P-150
Prognostic value of baseline biliary stents on outcomes in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the global NAPOLI-1 trial7
P-151
The effect of best response to prior anticancer therapy on efficacy outcomes in the NAPOLI-1 trial of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy8
P-152
Decreased appetite (DA) at baseline impacts prognosis in the NAPOLI-1 phase III study in metastatic pancreatic ductal adenocarcinoma (mPDAC)5
P-153
Symptoms reported at initial diagnosis of (metastatic) pancreatic adenocarcinoma ([m]PAC) in routine clinical practice and variation in frequencies across Europe1
P-167 (poster presentation)
More detailed data on each abstract can be found by visiting: View Source

About Pancreatic Cancer
Pancreatic adenocarcinoma is a disease with limited treatment options and is almost always fatal.11 At the time of diagnosis, more than 80 percent of people diagnosed with pancreatic adenocarcinoma have metastatic disease or locally advanced disease that cannot be removed with surgery.12 The disease has a median five-year survival rate of about five percent,9 and an median overall survival of typically less than a year, as illustrated by real-world European systematic review.10 The only curative treatment for pancreatic adenocarcinoma is surgical resection in the early stage, which can improve five-year survival to 10 percent.13

The signs and symptoms of pancreatic adenocarcinoma are non-specific (common presenting symptoms include jaundice, abdominal pain, weight loss, steatorrhoea and new-onset diabetes).9 Clear symptoms may not appear until the disease has spread locally or metastasized. As a result, most patients are not candidates for surgery upon diagnosis.12

Pancreatic adenocarcinoma accounts for less than three percent of all cancer cases,14 yet is the seventh leading cause of cancer death worldwide and the fourth in Europe.9 Worldwide, pancreatic cancer prognosis is typically poor, with an estimated 338,000 new cases and 331,000 deaths each year.11

About NAPOLI-1
NAPOLI-1 is the first global, randomized open-label Phase 3 trial to show extended overall survival in metastatic pancreatic adenocarcinoma after gemcitabine-based therapy through treatment with ONIVYDE combined with 5-FU and LV. Patients were enrolled at 76 sites in 14 countries across North America, Europe, Asia, South America and Australia. The study evaluated ONIVYDE (80 mg/m2), expressed as irinotecan hydrochloride trihydrate (which is the equivalent of 70 mg/m2 ONIVYDE expressed as irinotecan free base) in combination with 5-FU/LV administered intravenously every two weeks and as a monotherapy (120 mg/m2) administered every three weeks. Each ONIVYDE containing arm was compared to a control arm of 5-FU/LV.15

About liposomal irinotecan (nal-IRI)
Liposomal irinotecan (nal-IRI) is approved in the EU under the name ‘ONIVYDE.’ ONIVYDE is approved for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-FU/LV, in adult patients who have disease progression following gemcitabine-based therapy.16

Shire is responsible for the development and commercialization of ONIVYDE outside of the United States and Taiwan under an exclusive licensing agreement with Ipsen Biopharmaceuticals, Inc., an affiliate of Ipsen, (Euronext: IPN; ADR: IPSEY). Ipsen markets ONIVYDE in the United States after completion of the acquisition from Merrimack Pharmaceuticals.

ONIVYDE received US Food and Drug Administration (FDA) approval in October 2015 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have progressed following treatment with gemcitabine-based therapy. ONIVYDE product license was granted in Taiwan in March 2016, where PharmaEngine holds the commercialization rights.

Important Safety Information
The most common adverse reactions (incidence ≥20 percent) seen with ONIVYDE in combination with 5-FU/LV were: diarrhea, nausea, vomiting, decreased appetite, neutropoenia, fatigue, asthenia, anaemia, stomatitis and pyrexia.15 In the clinical study, Grade 3 or Grade 4 diarrhea occurred in 12.8 percent of patients receiving ONIVYDE in combination with 5-FU/LV. Early-onset (within one day of treatment) diarrhea occurred in 30 percent of patients on ONIVYDE combined with 5-FU/LV and was usually transient.15 Early-onset diarrhea was accompanied by cholinergic symptoms in 3.4 percent of patients taking ONIVYDE in combination with 5-FU/LV.15 Median time to late-onset diarrhea was eight days following the ONIVYDE dose.15 Of patients taking ONIVYDE combined with 5-FU/LV, 11 percent of patients discontinued treatment vs 7% of patients receiving 5-FU/LV alone.15