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Lilly and Merck Expand Immuno-Oncology Collaboration

On January 11, 2017 Eli Lilly and Company (NYSE: LLY) reported the expansion of an existing immuno-oncology collaboration with Merck, known as MSD outside the U.S. and Canada, through a subsidiary, to add a new study of Lilly’s LARTRUVO (olaratumab) with KEYTRUDA (pembrolizumab) in patients with previously treated advanced or metastatic soft tissue sarcoma (STS) (Press release, Eli Lilly, JAN 11, 2017, View Source [SID1234517345]).

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Notably, the U.S. Food and Drug Administration (FDA) recently granted accelerated approval for LARTRUVO (olaratumab injection, 10 mg/mL), in combination with doxorubicin, for the treatment of adults with STS with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery. LARTRUVO (olaratumab injection, 10 mg/mL), in combination with doxorubicin, also recently received conditional marketing authorization from the European Medicines Agency for the treatment of adults with advanced STS not amenable to curative treatment with surgery or radiotherapy and who have not been previously treated with doxorubicin.

"We look forward to further expanding our collaboration with Merck to include this combination study focused on advanced soft tissue sarcoma, a rare and difficult-to-treat disease with limited treatment options," said Sue Mahony, Ph.D., senior vice president and president, Lilly Oncology. "This collaborative study builds on the exciting data we have seen with olaratumab and supports our focus on investigating the potential of rational combinations to enhance efficacy and change the standards of care for people with cancer."

"Historic and present day scientific advances continue to reinforce the role of combination therapies in extending the lives of people with cancer," said Eric Rubin, M.D., vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. "Our collaboration with Lilly exemplifies our commitment to fully exploring combination regimens with KEYTRUDA to help arm physicians with the treatment tools they need to help their patients."

Lilly is the sponsor of the Phase 1 study and enrollment is expected to begin mid-2017. Financial details of the collaboration were not disclosed.

In addition to the study announced today, other ongoing trials between Lilly and Merck, through a subsidiary, include:

Studies of pemetrexed (plus carboplatin) and pembrolizumab in first-line nonsquamous non-small cell lung cancer (NSCLC), including a Phase 3 study that is currently enrolling patients;
A Phase 1 study examining the combination of ramucirumab with pembrolizumab in NSCLC, gastric cancer and bladder cancer;
A Phase 1 study examining the combination of necitumumab with pembrolizumab in NSCLC; and
A Phase 1 study examining the combination of abemaciclib, a CDK 4 and 6 inhibitor, with pembrolizumab. Based on the Phase 1 trial results, the collaboration has the potential to progress to Phase 2 trials in patients who have been diagnosed with either metastatic breast cancer or NSCLC.
Olaratumab (marketed under the brand name LARTRUVO) is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody that specifically binds PDGFR-α and prevents receptor activation. LARTRUVO exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models.

Pembrolizumab (marketed under the brand name KEYTRUDA) is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

NOTES TO EDITORS

About Sarcomas

Sarcomas are a diverse and relatively rare type of cancer that usually develop in the connective tissue of the body, which include fat, blood vessels, nerves, bones, muscles, deep skin tissues and cartilage. Soft tissue sarcoma is a complex disease with multiple subtypes, making it very hard to diagnose and difficult to treat. For decades, there have been no front-line therapeutic advancements for STS that have improved overall survival. According to the American Cancer Society, in 2015, there were an estimated 12,000 new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone.

INDICATION

LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

This indication is approved under Accelerated Approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR LARTRUVO

Warnings and Precautions

Infusion-Related Reactions

Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N = 485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.
Embryo-Fetal Toxicity

Based on animal data and its mechanism of action, LARTRUVO can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of platelet-derived growth factor receptor alpha (PDGFR-α) signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LARTRUVO and for 3 months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities

The most commonly reported adverse reactions (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs 3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs 25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs 40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs 23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and headache (20% vs 9%; 0% vs 0%).
The most common laboratory abnormalities (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%; 44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs 28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia (21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs 3%).
Use in Specific Populations

Lactation: Because of the potential risk for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LARTRUVO and for at least 3 months following the last dose.
For more information about LARTRUVO, please see full Prescribing Information at View Source

OR HCP ISI 19OCT2016

Alligator presents at JP Morgan, Biotech Showcase, San Fransisco

On January 10, 2017 Alligator presented the corporate presentation (Press release, Alligator Bioscience, JAN 10, 2017, View Source [SID1234538700]).

LabCorp to Acquire Assets of Mount Sinai Health System Clinical Outreach Laboratories

On January 10, 2017 Laboratory Corporation of America Holdings (LabCorp) (NYSE: LH), a world leading life sciences company, and the Mount Sinai Health System (Mount Sinai), one of the largest health systems in metropolitan New York City, reported that they have entered into a definitive agreement for LabCorp to acquire assets of Mount Sinai’s Clinical Outreach Laboratories (Press release, LabCorp, JAN 10, 2017, View Source;p=irol-newsArticle&ID=2236528 [SID1234518885]). When the transaction is complete, LabCorp will be available to provide comprehensive laboratory services to physicians and patients that currently use Mount Sinai’s outreach laboratory.

"LabCorp has successfully provided comprehensive health system solutions for over three decades," said David P. King, chairman and chief executive officer of LabCorp. "This transaction, giving us the opportunity to serve an anchor health system in the critical New York metro market, provides us even broader opportunity to improve health and lives through the delivery of world class diagnostics."

Mount Sinai will continue to provide laboratory testing for patients registered at its hospitals and ambulatory facilities as inpatients or outpatients, as well as laboratory testing services for physicians in their professional practices in the areas of anatomic pathology, molecular pathology and genetics. LabCorp will offer clinical pathology testing, including cytology and cytology-related molecular testing. Seven patient service centers currently operated by Mount Sinai will be added to LabCorp’s existing network of 120 patient service centers in the metropolitan New York City area. The parties are also vigorously exploring opportunities to collaborate on projects involving companion diagnostics, clinical trials and medical education.

"LabCorp was selected for its depth and breadth of services and track record of high quality," said Carlos Cordon-Cardo, M.D., Ph.D., Irene Heinz Given and John LaPorte Given professor and chairman, Department of Pathology, Mount Sinai Health System. "Their unparalleled reputation and success ensures our patients will continue to have access to high-quality, high-value and convenient testing services."

"Customers and patients will quickly see the advantages of our differentiators," said William B. Haas, senior vice president and co-leader of LabCorp Diagnostics. "Only LabCorp can offer access to clinical trials and research through Covance Drug Development, enhanced IT and data analytics, standardized testing platforms and broad patient access."

"We are confident this transaction will provide great benefits for our patients and physicians and allow Mount Sinai to continue to invest in our core strategic programs," said Donald Scanlon, chief financial officer and chief of corporate services, Mount Sinai Health System. "LabCorp’s proven track record of service excellence, breadth of diagnostic capabilities, and cost-efficiency will benefit our community now and in years to come."

The transaction, which has already received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, is expected to close in the first quarter of 2017. Other terms of the transaction were not disclosed.

Citi acted as exclusive advisor to the Mount Sinai Health System in connection with the clinical outreach assets sold in this transaction.

Integra LifeSciences to Acquire Derma Sciences Inc. and Announces Preliminary Fourth Quarter and Full Year 2016 Financial Results and 2017 Outlook

On January 10, 2017 Integra LifeSciences Holdings Corporation (Nasdaq:IART), a global leader in medical technology, reported that it has signed a definitive agreement to acquire Derma Sciences Inc. (Nasdaq:DSCI) for a price of $7.00 per share of Derma Sciences common stock in cash (Press release, Integra LifeSciences, JAN 10, 2017, View Source [SID1234517585]).

"Derma Sciences’ amniotic tissue-based platform technology further broadens Integra’s regenerative technology capabilities and builds upon our 3×3 wound care strategy," said Peter Arduini, Integra’s president and chief executive officer. "The addition of a complementary portfolio of wound care products, including an amniotic product with reimbursement in the wound care channel, allows us to further drive scale in the advanced wound care market."

Under the agreement, Integra will commence a tender offer to purchase all of the outstanding shares of Derma Sciences common stock for $7.00 per share in cash. Integra will also offer to purchase the outstanding shares of Derma Sciences preferred stock for an amount equal to its liquidation preference per share. The tender offer will be followed by a merger of Derma Sciences with a newly formed subsidiary of Integra. The companies expect to complete the transaction at the end of the first quarter of 2017, subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of outstanding shares of Derma Sciences common stock and preferred stock. Integra expects to use its existing credit facility to finance the transaction.

BofA Merrill Lynch acted as exclusive financial advisor and Latham & Watkins LLP acted as legal advisor to Integra.

Preliminary Fourth Quarter and Full Year 2016 Financial Results

Integra is also announcing today that it expects its fourth quarter 2016 total revenue to be approximately $256 million, resulting in full-year 2016 revenue of approximately $992 million, at the low end of the previously provided guidance range. Integra expects to report fourth-quarter 2016 organic revenue growth, which excludes the impact of foreign currency changes and revenue from discontinued and acquired products, of approximately 7.0%, and full-year 2016 organic growth of approximately 9.0%.

The Company expects fourth-quarter 2016 GAAP and adjusted diluted earnings per share to be at or above the mid-point of the prior guidance range of $0.32 to $0.35 and $0.50 to $0.53 post-stock split, respectively. This implies full-year 2016 GAAP and adjusted diluted earnings per share at or above the mid-point of the range of $0.91 to $0.94 and $1.73 to $1.77 post-stock split, respectively. At this point during our year-end close activities, the Company is not able to provide a breakdown of the components of the non-GAAP adjustments, but preliminarily estimates these to total $0.82 per share for the full year 2016.

Operating cash flow, excluding approximately $43 million of accreted interest payment associated with the 2016 Convertible Notes that matured in December 2016, and free cash flow were strong. The Company expects to be slightly above the high end of the previous guidance range for both metrics, above $145 million operating cash flow and above $105 million for free cash flow. The difference between operating cash flow and free cash flow is a preliminary estimate of $40 million for capital expenditures.

2017 Financial Guidance

The Company is also providing preliminary 2017 revenue and adjusted earnings per share guidance for 2017. Integra expects full-year 2017 organic revenue growth to be between 7% and 8.5%. This implies a revenue range of approximately $1.05 billion to $1.07 billion, inclusive of an unfavorable impact from foreign currency of approximately one percent at current exchange rates.

Full-year 2017 earnings per share are expected to grow low double digits, exclusive of the unfavorable impact expected from foreign currency. The Company expects full-year 2017 adjusted earnings per share to be in the range of $1.91 to $1.97, taking into account a two cent negative impact from foreign currency. The Company is still in the process of reconciling estimates for full-year 2017 GAAP EPS projections and will provide this information and other additional information when full 2016 financial results are reported on February 22, 2017.

This preliminary 2017 guidance does not include the acquisition of Derma Sciences, Inc., which has not closed. Assuming a closing date at the end of the first quarter of 2017, Integra expects the acquisition to add approximately $65 million in revenue and to be dilutive to adjusted earnings per share by approximately three cents during 2017. The acquisition is expected to turn accretive to adjusted earnings in 2018, and to reach our return on invested capital hurdle by the end of the third year.

Announcement on submission of the Clinical Trial Plan Notification for phase I/II clinical trial of CAR gene therapy in Japan

On January 11, 2017 Takara Bio Inc. (Takara Bio), reported that it has submitted the Clinical Trial Notification for regenerative medicines to PMDA (Pharmaceuticals and Medical Devices Agency), Japanese regulatory agency, to conduct phase I/II clinical trial for gene therapy using CD19 Chimeric Antigen Receptor (CAR) (Development code: TBI-1501) targeting relapsed and refractory acute lymphoblastic leukemia (ALL) in Japan (Press release, Takara Bio, JAN 10, 2017, View Source [SID1234517405]). In the clinical trial, CAR which recognizes CD19, a protein expressing on the surface of malignant lymphocyte, is transferred ex-vivo to lymphocytes of patients with adult ALL, and the gene-modified lymphocytes are infused back to the patients. The patients will be monitored for safety and efficacy. The Takara Bio’s method of gene transduction and T-cell expansion using RetroNectin, and Takara Bio’s original retroviral vectors for transduction of CD19-CAR will be used during the cell processing for the clinical trial. After the clearance, the protocol will be reviewed by each IRB (Institutional Review Board) and the study will be initiated. Takara Bio aims to commercialize the CD19-CAR gene therapy in the fiscal year 2020, by obtaining an early approval utilizing the conditional and term-limited approval system for regenerative medicines under The Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical devices.

【Overview of the Clinical Trial】
Study name Multicenter Phase I/II Clinical Trial of TBI-1501 for elapsed and refractory CD19-positive B-cell Acute Lymphoblastic Leukemia
Condition Patients with elapsed and refractory CD19-positive B-cell Acute Lymphoblastic Leukemia
Main Endpoint Phase I Clinical trial
1) Safety
2) TBI-1501 Persistency
Phase II Clinical trial
1) Efficacy
Estimated Enrollment 21 (maximum 24)
Duration Mar 2017 – Mar 2020
Site Jichi Medical University and others, total 6 sites