On March 31, 2017 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported it has filed its 2016 Annual Report on Form 20-F with the U.S. Securities and Exchange Commission (Press release, Can-Fite BioPharma, MAR 31, 2017, View Source [SID1234518351]).

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!

Clinical Development Program and Corporate Highlights Include:

● Piclidenoson (CF101) – Phase III Trials in Rheumatoid Arthritis & Psoriasis to Commence

Rheumatoid Arthritis: Can-Fite expects to be ready to commence its pivotal Phase III ACRobat trial of Piclidenoson in the second quarter of 2017. Piclidenoson is being developed as a first line therapy and replacement for the current gold standard, Methotrexate (MTX), the most widely used drug for rheumatoid arthritis. ACRobat will enroll approximately 500 patients in Europe, Canada and Israel. The estimated cost of the entire Phase III study is approximately $5 million. This includes the cost of global clinical research organizations that have been engaged to help conduct ACRobat. The required supply of Piclidenoson has already been manufactured and paid.

Rheumatoid arthritis is a treatment market forecast to reach $34.6 billion by 2020.

Psoriasis: During the fourth quarter of 2016 Can-Fite reached an agreement with the European Medicines Agency (EMA) on the final design of a global pivotal Phase III trial for Piclidenoson in the treatment of psoriasis. The Phase III trial will investigate the efficacy and safety of Piclidenoson compared to placebo as its primary endpoint and as compared to apremilast (Otezla) as its secondary endpoint in approximately 400 patients with moderate-to-severe plaque psoriasis. Can-Fite expects to submit its clinical protocol to Institutional Review Boards (IRBs) in the fourth quarter of 2017.

The psoriasis market is forecast to be $8.9 billion in 2018 and Otezla sales are estimated to be $2.35 billion by 2020.

● Namodenoson (CF102) – Phase II NAFLD/NASH Trial to Commence; Phase II Liver Cancer Trial Nearing Completion; Upfront Payment Received in $3 million-Plus-Royalties Distribution Deal in South Korea

Can-Fite signed a distribution agreement with Chong Kun Dang Pharmaceuticals (CKD) for the exclusive right to distribute Namodenoson for the treatment of liver cancer in South Korea during the fourth quarter of 2016. Can-Fite has received a $500,000 upfront payment from CKD as part of its agreement valued at up to $3,000,000 in upfront and milestone payments. Can-Fite is entitled to 23% royalties on net sales following regulatory approval of Namodenoson in South Korea. CKD also negotiated a right of first refusal to distribute Namodenoson for other indications for which Can-Fite develops Namodenoson.

Liver Cancer: Can-Fite continues to enroll and dose patients in its global Phase II study of Namodenoson in the treatment of hepatocellular carcinoma, the most common form of liver cancer. A total of approximately 78 patients are expected to be enrolled in the U.S., Europe, and Israel. Completion of patient enrollment is expected in the second quarter of 2017.

Liver cancer drugs are expected to generate $1.4 billion in sales in 2019.

NAFLD/NASH: Leading IRBs in Israel cleared Can-Fite to commence patient enrollment in its Phase II clinical trial of Namodenoson in the treatment of non-alcoholic fatty liver disease (NAFLD), the precursor to non-alcoholic steatohepatitis (NASH), in January 2017. This approval came shortly following Can-Fite’s submission of the Phase II protocol in the fourth quarter of 2016 to IRBs, including Hadassah Medical Center and Rabin Medical Center, which are expected to participate in the planned study by enrolling and treating patients. Patient enrollment is expected to begin in the second quarter of 2017.

During the fourth quarter of 2016, Can-Fite announced new preclinical data showing Namodenoson inhibited, in a dose dependent manner, the growth and proliferation of liver fibrosis cells. This suggests Namodenoson has an anti-fibrotic effect and provides further support for the drug’s development as an agent to combat NAFLD.

By 2025, the addressable pharmaceutical market for NASH is estimated to reach $35-40 billion.

● CF602 – Patent Estate Expanded in Sexual Dysfunction

The U.S. Patent and Trademark Office issued to Can-Fite a patent during the fourth quarter of 2016 covering A3 adenosine receptor (A3AR) ligands for use in the treatment of erectile dysfunction. The patent addresses methods for treating erectile dysfunction with different A3AR ligands including Can-Fite’s erectile dysfunction drug candidate, CF602. With this new broader patent protection, Can-Fite has made a strategic decision to investigate additional compounds, owned by the Company, for the most effective and safest profile in this indication. As such, the Company postponed its planned Investigational New Drug (IND) submission for this indication.

"In the coming months, we are eager to advance our two Phase III trials for Piclidenoson in rheumatoid arthritis and psoriasis, both indications in which there is a dearth of safe and effective drugs that can be used in the long-term treatment of these auto-immune diseases. With our Phase II liver cancer trial for Namodenoson nearing completion, we are ready to start enrolling patients in our Phase II study of Namodenoson in the treatment of NAFLD/NASH. Both Piclidenoson and Namodenoson are strong candidates for partnering and distribution deals in various geographic markets," stated Can-Fite CEO Dr. Pnina Fishman.

Revenues for the twelve months ended December 31, 2016 were NIS 0.65 million (U.S. $0.17 million) compared to revenues of NIS 0.64 million (U.S. $0.17 million) during the year ended December 31, 2015. The revenues during 2016 were mainly due to the recognition of a portion of the NIS 5.14 million (CAD 1.65 million) advance payment received in March 2015 under the distribution agreement with Cipher and a small amount due to the recognition of a portion of the NIS 1.9 million (U.S. $0.5 million) advance payment received in December 2016 under the distribution agreement with CKD.

Research and development expenses for the twelve months ended December 31, 2016 were NIS 23.38 million (U.S. $6.08 million) compared with NIS 15.05 million (U.S. $3.91 million) for the same period in 2015. Research and development expenses for the year ended 2016 comprised primarily of expenses associated with the Phase II study for Namodenoson as well as expenses for ongoing studies of Piclidenoson. The increase is primarily due to costs associated with preparations of the Piclidenoson Phase III studies in the treatment of rheumatoid arthritis and psoriasis and costs associated with the ongoing clinical trial of Namodenoson for treatment of liver cancer. We expect that research and development expenses will increase through 2017 and beyond.

General and administrative expenses were NIS 10.48 million (U.S. $2.73 million) for the twelve months ended December 31, 2016 compared to NIS 10.63 million (U.S. $2.76 million) for the same period in 2015. The minor decrease is primarily due to a decrease in professional services. We expect that general and administrative expenses will remain at the same level through 2017.

Financial income, net for the twelve months ended December 31, 2016 aggregated NIS 6.31 million (U.S. $1.64 million) compared to financial income, net of NIS 5.29 million (U.S. $1.38 million) for the same period in 2015. The increase in financial income, net in the year ended December 31, 2016 was mainly due to the fact that during 2016 we did not record any share issuance expenses unlike in 2015.

Can-Fite’s net loss for the twelve months ended December 31, 2016 was NIS 27.01 million (U.S. $7.02 million) compared with a net loss of NIS 19.77 million (U.S. $5.14 million) for the same period in 2015. The increase in net loss for 2016 was primarily attributable to an increase in research and development expenses.

As of December 31, 2016, Can-Fite had cash and cash equivalents of NIS 31.2 million (U.S. $8.12 million) as compared to NIS 66.03 million (U.S. $17.17 million) at December 31, 2015. In addition, in January of 2017, Can-Fite raised U.S. $5 million in a registered direct offering. The decrease in cash during the twelve months ended December 31, 2016 is mainly due to an increase in research and development expenses.

For the convenience of the reader, the reported NIS amounts have been translated into U.S. dollars, at the representative rate of exchange on December 31, 2016 (U.S. $ 1 = NIS 3.845).

The Company’s consolidated financial results for the twelve months ended December 31, 2016 are presented in accordance with International Financial Reporting Standards.

The 2016 Annual Report can be found on the Company’s website at www.canfite.com as well as on the SEC website at www.sec.gov. In addition, security holders may request a hard copy of the Annual Report, which includes the Company’s complete audited financial statements, free of charge. Requests can be made by contacting Can-Fite Investor Relations at 10 Bareket Street, Kiryat Matalon, Petah-Tikva 4951778, Israel or by phone at +972-3-9241114.

On March 31, 2017 Radius Health, Inc. (Nasdaq:RDUS), a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases, reported that it will present new preclinical data on elacestrant (RAD1901), an oral selective estrogen degrader, in ER-positive breast cancer and two posters regarding RAD140, an oral non-steroidal selective androgen receptor modulator, at the AACR (Free AACR Whitepaper) Annual Meeting 2017 on April 1-5, 2017 at the Walter E. Washington Convention Center in Washington D.C (Press release, Radius, MAR 31, 2017, View Source [SID1234518349]).

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!

Details on the three poster presentations are as follows:

Abstract Title: Impact of oral selective estrogen receptor degrader elacestrant (RAD1901) in preclinical models of endocrine sensitive/resistant breast cancer (preclinical)
Abstract Number: 4160
Session Title: Novel Mechanisms 2
Session Date: April 4, 2017
Session Time: 1:00 — 5:00 PM

Abstract Title: RAD140, an orally available selective androgen receptor modulator, inhibits the growth of AR/ER positive breast cancer cell line- and patient-derived xenograft models
Abstract Number: 3608
Session Title: Endocrine Oncology Therapies
Session Date: April 4, 2017
Session Time: 8:00 AM — 12:00 PM

Abstract Title: RAD140, a selective androgen receptor modulator, has a differentiated mechanism of action in AR/ER positive breast cancers
Abstract Number: 3609
Session Title: Endocrine Oncology Therapies
Session Date: April 4, 2017
Session Time: 8:00 AM — 12:00 PM

Abstracts for each poster and additional information on the meeting can be found on the AACR (Free AACR Whitepaper) website: www.aacr.org/.

On March 31, 2017 Incyte Corporation (Nasdaq:INCY) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported additional details of their clinical development program investigating the combination of epacadostat, Incyte’s investigational oral selective IDO1 enzyme inhibitor, with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients across five tumor types: metastatic melanoma, non-small cell lung cancer (NSCLC), bladder cancer, renal cell carcinoma (RCC), and squamous cell carcinoma of the head and neck (SCCHN) (Press release, Incyte, MAR 31, 2017, View Source [SID1234518348]).
This Smart News Release features multimedia. View the full release here: View Source

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!

The expanded collaboration now includes seven pivotal studies:
A Phase 3 study in metastatic melanoma (trial underway);
two Phase 3 studies in first-line NSCLC, including both PD-L1 high-expressing and PD-L1 unselected populations;
two Phase 3 studies in bladder cancer, including one in first-line bladder cancer and one in second-line bladder cancer;
a Phase 3 study in first-line RCC; and
a Phase 3 study in first-line SCCHN.
Incyte and Merck will share responsibilities for funding these pivotal studies, and Merck will be responsible for conducting the trials.

"We are pleased to announce further details of our collaboration with Merck and to be moving forward with multiple Phase 3 studies in these four additional tumor types as quickly as possible," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We look forward to our continued clinical collaboration, the initiation of these additional pivotal trials and to further exploring the potential of this novel immune-therapy combination as a treatment for patients with cancer."
"Our clinical trial program with Incyte represents an important part of our multi-pronged efforts to investigate the potential for KEYTRUDA (pembrolizumab) in combination with promising compounds, such as epacadostat," said Dr. Roy Baynes, senior vice president, head of clinical development, and Chief Medical Officer, Merck Research Laboratories. "Through these trials, our long-term goal is to help make a difference in the lives of people with a wide range of cancers."
About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating KEYTRUDA in combination with epacadostat or placebo for the first-line treatment of patients with advanced or metastatic melanoma, is also underway.
About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that reverses tumor-associated immune suppression and restores effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor KEYTRUDA improved response rates compared with studies of the immune checkpoint inhibitors alone.
About KEYTRUDA (pembrolizumab)
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. KEYTRUDA 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.
KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single-dose vial.
KEYTRUDA (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA (pembrolizumab) is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Head and Neck Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA (pembrolizumab) when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with

KEYTRUDA vs the risk of possible organ rejection in these patients.
KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor-blocking antibody before transplantation. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA (pembrolizumab).

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL and treatment was interrupted due to adverse reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
There is limited experience in pediatric patients. In a study of 40 pediatric patients with advanced melanoma, PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma, patients were treated with KEYTRUDA for a median of 43 days (range 1 to 414 days), with 24 patients (60%) receiving treatment for 42 days or more. The safety profile in pediatric patients was similar to that seen in adults treated with KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

On March 31, 2017 Amgen (NASDAQ:AMGN) reported that new preclinical data from its oncology portfolio will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 1-5, 2017, in Washington, D.C (Press release, Amgen, MAR 31, 2017, View Source [SID1234518347]). These data provide insights into the potential of Amgen’s half-life optimized bispecific T cell engager (BiTE) immunotherapy platform across different cancers, as well as the local and systemic immune effects from combining Amgen’s oncolytic virus with a CTLA-4 inhibitor.

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!

Preclinical data from Amgen’s latest oncology candidate to enter clinical trials (AMG 176) will also be presented. AMG 176 is a potent, highly selective and reversible Mcl-1 inhibitor. A variety of studies have demonstrated that hematologic malignancies, such as multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma, are particularly sensitive to Mcl-1 inhibition.

"AACR has always been an important meeting for sharing some of our latest advances in cancer research and 2017 is no exception. This year’s data underscores our commitment to Amgen’s evolving oncology portfolio and to the discovery and development of innovative new therapies," said David Reese, M.D., senior vice president of Discovery Research (interim) and Translational Sciences at Amgen. "In addition to sharing new data for some of our more advanced compounds, we also look forward to sharing research around our first-in-class Mcl-1 inhibitor, a small molecule being investigated for its potential use in patients with hematologic malignancies for which there continues to be a need for new treatment options."

Abstracts are available and can be viewed on the AACR (Free AACR Whitepaper) website at View Source Identified below are selected abstracts of interest on Amgen research.

Mcl-1 Inhibition:

The discovery and preclinical characterization of AMG 176: A first-in-class Mcl-1 inhibitor in clinical development for multiple myeloma
Abstract #DDT01-01, Oral Presentation, Sunday, April 2 from 1–1:24 p.m. ET at Walter E. Washington Convention Center, East Salon A-B, Level 1
Combined targeting of MEK and MCL-1 induces apoptosis and tumor regression of KRAS mutant NSCLC
Abstract #2163, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 7
Preclinical evaluation of AMG 176, a novel, potent and selective Mcl-1 inhibitor with robust anti-tumor activity in Mcl-1 dependent cancer models
Abstract #2027, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 1
BiTE Antibody Construct:

Generation of half-life extended anti-CD33 BiTE antibody constructs compatible with once-weekly dosing
Abstract #55, Poster Session, Sunday, April 2 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 3
Preclinical evaluation of a BiTE antibody construct with extended half-life that targets the tumor differentiation marker mesothelin
Abstract #3630, Poster Session, Tuesday, April 4 from 8 a.m. – noon ET at Walter E. Washington Convention Center, Halls A-C, Section 26
BiTE antibody constructs for the treatment of SCLC
Abstract #3632, Poster Session, Tuesday, April 4 from 8 a.m. – noon ET at Walter E. Washington Convention Center, Halls A-C, Section 26
Immuno-Oncology:

OncoVEXmGM-CSF (HSV-1 modified similarly to talimogene laherparepvec) icombination with CTLA-4 blockade leads to both local and systemic efficacy in a murine syngeneic model of metastatic melanoma
Abstract #4566, Poster Session, Tuesday, April 4 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 25
Growth Inhibitory Pathway:

Selective MET kinase inhibition in MET-dependent glioma models
Abstract #2077, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 4
About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

On March 31, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has granted full approval for Tagrisso (osimertinib) 80mg once-daily tablets, for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after an EGFR tyrosine kinase inhibitor (TKI) therapy (Press release, AstraZeneca, MAR 31, 2017, View Source [SID1234518328]). Tagrisso is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation, and efficacy data suggest it may be a new standard of care for these patients.

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!

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "By following the science, we aim to turn lung cancer into a chronic, manageable disease for patients and this milestone brings us one step closer to that ambition. The FDA’s full approval reinforces the potential of Tagrisso to become the standard of care for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed on or after first-generation EGFR-TKI therapy."

The full approval in the US is based on data from the randomised, Phase III AURA3 trial, in which Tagrisso significantly improved progression-free survival (PFS) versus platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk reduction; 95% Confidence Interval [CI]: 0.23; 0.41; P<0.001). The results of this trial were recently presented at the 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, and published in The New England Journal of Medicine.

In AURA3 the most common (>20%) adverse reactions observed in Tagrisso-treated patients were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Dose reductions occurred in 2.9% of patients treated with Tagrisso. The most frequent adverse reactions that led to dose reductions or interruptions were prolongation of the QT interval as assessed by ECG (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious adverse reactions were reported in 18% of patients treated with Tagrisso and 26% of patients in the chemotherapy group. No single serious adverse reaction was reported in 2% or more patients treated with Tagrisso.

Tagrisso was granted Fast Track, Breakthrough Therapy and Priority Review designations by the US FDA, and received Accelerated Approval for this indication in 2015 based on tumour response rate and duration of response.

About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined. Among patients with NSCLC, 20% to 40% have brain metastases at some time during the course of their disease. Patients who have the EGFRm form of NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the secondary mutation, T790M.

About Tagrisso
Tagrisso (osimertinib) 40mg and 80mg once daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.

Tagrisso is a third generation, irreversible EGFR tyrosine kinase inhibitor designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the central nervous system (CNS). Tagrisso is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.