Bristol-Myers Squibb Presents New Data at IASLC 17th World Conference on Lung Cancer Underscoring Progress and Leadership in Broad Lung Development Program

On November 16, 2016 Bristol-Myers Squibb Company (NYSE:BMY) reported new data to be presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria from December 4-7 (Press release, Bristol-Myers Squibb, NOV 16, 2016, View Source [SID1234516636]). Among the key data to be presented, studies evaluating Opdivo (nivolumab) monotherapy and in combination with Yervoy (ipilimumab) in two types of lung cancer highlight the company’s commitment to addressing high unmet medical needs.

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Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb, commented, "We believe Immuno-Oncology combinations may help improve outcomes for patients with lung cancer and have a strong scientific rationale for studying the Opdivo and Yervoy combination therapy. At the WCLC meeting, we will share data investigating this regimen in first-line non-small cell lung cancer and previously treated small cell lung cancer, as well as other important data from our broad thoracic development program."

The full set of Bristol-Myers Squibb-sponsored data to be presented include:

First-line Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Patients With Advanced NSCLC: Long-term Outcomes From CheckMate -012
Presenter: S. Gettinger
Oral Session: Immunotherapy Checkpoint Inhibitors in Advanced NSCLC; Monday, December 5, 11:00 CET, Room C8
Nivolumab Alone or With Ipilimumab in Recurrent Small Cell Lung Cancer: Two-year Survival and Updated Analyses From the CheckMate -032 Trial
Presenter: M. Hellmann
Mini Oral Session: Immunotherapy Combinations; Tuesday, December 6, 14:50 CET, Room Strauss 2
Analysis of Early Survival in Patients With Advanced Non-squamous NSCLC Treated With Nivolumab vs Docetaxel in CheckMate -057
Presenter: S. Peters
Oral Session: Immunotherapy Checkpoint Inhibitors in Advanced NSCLC; Monday, December 5, 11:45 CET, Room C8
Is Nivolumab Safe and Effective in Elderly and PS2 Patients With Non-small Cell Lung Cancer? Results of CheckMate -153
Presenter: D. Spigel
Poster Session with Presenters: Wednesday, December 7, 14:30 CET, Hall B
Demonstrating Life Expectancy Gains With Immuno-Oncology Therapies
Presenter: R. Figlin
Mini Oral Session: Immunotherapy in Advanced NSCLC: Biomarkers and Costs; Tuesday, December 6, 17:00 CET, Room Strauss 2
Prognostic Factors for Overall Survival Among Patients With Advanced/Metastatic Non-small Cell Lung Cancer
Presenter: K. Verleger
Poster Session with Presenters: Tuesday, December 6, 14:30 CET, Hall B
Checkmate 384: A Phase 3b/4 Dose-frequency Optimization Trial of Nivolumab in Advanced or Metastatic Non-small Cell Lung Cancer
Presenter: R. Harris
Poster Session with Presenters: Wednesday, December 7, 14:30 CET, Hall B
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.

U.S. FDA APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

Please refer to the end of the Important Safety Information for a brief description of the patient populations studied in the CheckMate trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. 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.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO . The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

CheckMate Trials and Patient Populations
Checkmate 067 – advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 – advanced melanoma; Checkmate 017 – squamous non-small cell lung cancer (NSCLC); Checkmate 057 – non-squamous NSCLC; Checkmate 025 – renal cell carcinoma; Checkmate 205/039 – classical Hodgkin lymphoma; Checkmate 141 – squamous cell carcinoma of the head and neck.
Please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions, for YERVOY.

Please see U.S. Full Prescribing Information for OPDIVO.

Heat Biologics to Present Topline HS-410 Phase II Bladder Cancer Results at the Society of Urological Oncology Annual Meeting

On November 16, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), a leader in the development of gp96-based immunotherapies that are designed activate a patient’s immune system to fight cancer, reported that it will present a poster reporting topline results, including primary endpoint data, from the Phase II trial evaluating HS-410 (vesigenurtacel-L) in combination with standard of care, Bacillus Calmette-Guérin (BCG), in the treatment of non-muscle invasive bladder cancer (NMIBC) at the Society of Urology Annual Meeting, in San Antonio, TX, on Wednesday, Nov 30th (Press release, Heat Biologics, NOV 16, 2016, View Source [SID1234516626]). The poster will be presented by study principal investigator, Gary Steinberg, MD, The Bruce and Beth White Family Professor of Surgery and Director of Urologic Oncology at The University of Chicago Medical Center.

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Poster Presentation Details:

Title: Top-Line Results from Vesigenurtacel-L (HS-410) in Combination with BCG from a Randomized, Blinded Phase 2 Trial in Patients with Non-Muscle Invasive Bladder Cancer (NMIBC)

Date and Time: November 30, 2016, 5:30-7:15PM EST (4:30-6:15PM CST)

Poster Number: 21

The abstract can be viewed in the searchable online program at: View Source

American Medical Association’s USAN & World Health Organization’s INN Approve
“Namodenoson” as Generic Name for Can-Fite’s Liver Drug CF102

On November 16, 2016 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs being developed to treat inflammatory diseases, cancer and sexual dysfunction, reported that the United States Adopted Names Council (USAN) of the American Medical Association and the World Health Organization’s International Nonproprietary Name (INN) group have accepted the proposed generic name "Namodenoson" for its drug candidate, CF102 (Filing, 6-K, Can-Fite BioPharma, NOV 16, 2016, View Source [SID1234516623]).

"Assignment of a unique generic name is a very meaningful move forward for our liver cancer and NASH drug candidate, CF102. With both Fast Track and Orphan Drug status in the U.S. as a second line treatment for hepatocellular carcinoma, the Company is conducting a global Phase II liver cancer study. With a growing IP estate around the compound, along with strong pre-clinical data for its potential treatment of non-alcoholic fatty liver disease (NAFLD), the precursor to non-alcoholic steatohepatitis (NASH), we view CF102 as a key asset in our portfolio as evidenced by the recent multi-million dollar distribution agreement in South Korea for CF102," stated Can-Fite CEO Dr. Pnina Fishman.

The United States Adopted Names (USAN) Council, part of the American Medical Association (AMA), is responsible for selecting simple, informative and unique nonproprietary (generic) drug names. The World Health Organization’s International Nonproprietary Names (INN) facilitates the identification of pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property.

About Namodenoson (CF102)

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In Can-Fite’s pre-clinical and clinical studies, Namodenoson has demonstrated a robust anti-tumor effect via deregulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells. Based on preclinical data showing Namodenoson has strong liver protective properties, Can-Fite intends to initiate a Phase II study in NASH. Can-Fite has received Orphan Drug Designation for Namodenoson in Europe and the U.S., as well as Fast Track Status in the U.S. as a second line treatment for hepatocellular carcinoma.

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Genexine Enters into Clinical Research Collaboration with MSD

On November 16, 2016 Genexine Inc., a clinical stage biotechnology company developing innovative biologics, reported that it has entered into a clinical research collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada), for the assessment of Genexine’s GX-188E, HPV therapeutic DNA vaccine, in combination with MSD’s anti-PD-1 therapy, Keytruda (pembrolizumab), for the treatment of patients with HPV-induced cancers (Press release, Genexine, NOV 16, 2016, View Source [SID1234516672]).

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Under the terms of the agreement between Genexine and MSD, through a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Genexine will conduct a Phase 1b/2a clinical trial to access safety and efficacy of the combination therapy, and MSD will provide clinical supplies of Keytruda and offer support to the study. The agreement also includes provision for potential expansion to include Phase III registration studies in the same indication. Additional details were not disclosed.

Immuno-oncology is a rapidly evolving field of medicine designed to improve the ability of a patient’s immune system to detect and destroy tumors. The purpose of the study is to investigate which combination modalities of treatment will work best in patients with advanced HPV-induced cervical cancer. An objective response rate (ORR) of 12.5% was observed in a Keytruda clinical trial in patients with advanced cervical squamous cell cancer. Genexine expects that Keytruda is well suited to complement its HPV therapeutic DNA vaccine and that the combination with GX-188E can increase those response rates.

Gleaning from the trial in CIN, the Phase 1b/2a cancer study is scheduled to begin in the first half of 2017 with plans to enroll up to 40 patients. GX-188E induces T cells specific to E6/E7 protein originated from HPV type 16 and 18 and preclinical results for the combination therapy show the potential that the induced disease-specific T cells will work synergistically with anti-PD1 Ab. The combination trial with Keytruda and GX-188E will test to replicate animal POC in human to increase T cell specific immunotherapy.


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


▶ About GX-188E:
GX-188E, currently being developed in Phase 2 clinical trials, is a HPV therapeutic DNA vaccine for cervical intraepithelial neoplasia (CIN) and HPV-induced cancers caused by persistent infection by high-risk HPV types, 16/18. A Phase I study demonstrated that GX-188E, a rationally designed HPV DNA vaccine to target HPV antigens preferentially on dendritic cells, elicited significant E6/E7 specific IFN-γ-producing T-cell responses in all CIN3 patients when administered intramuscularly by electroporation. Seven out of nine patients had complete regression of their CIN3 lesions, viral clearance, and exhibited enhanced antigen-specific polyfunctional CD8 T-cell responses within 36 weeks of follow-up. These results were published in October 2014 in Nature Communications.

PALOMA-2 Phase 3 Study Published In The New England Journal Of Medicine Demonstrates Clinical Benefit Of Pfizer’s IBRANCE® (palbociclib) In First-Line ER+, HER2- Metastatic Breast Cancer

On November 16, 2016 Pfizer Inc. (NYSE:PFE) reported that detailed results from the Phase 3 PALOMA-2 trial were published in The New England Journal of Medicine (Press release, Pfizer, NOV 16, 2016, View Source [SID1234516660]).

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These data, presented at the 52nd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June, further demonstrate the clinical benefit of IBRANCE (palbociclib) as initial therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer. The PALOMA-2 study showed the combination of IBRANCE and letrozole extended progression-free survival (PFS), or the amount of time before tumor growth, by more than 10 months compared with letrozole plus placebo. Further, the study demonstrated that the median PFS of the IBRANCE and letrozole combination exceeded two years – making it the first and only treatment for this population of women to do so in a randomized Phase 3 study.1

"The median PFS of more than two years observed in this study is unprecedented for this patient population," said Veronique Dieras, M.D., medical oncologist and head of clinical research, Clinical Investigational Unit Chef de Service Recherche Clinique, Unité d’Investigation Clinique Department of Medical Oncology, Institut Curie, Paris, France. "Building on the Phase 2 PALOMA-1 data, the results of PALOMA-2 provide additional evidence that the combination of IBRANCE and letrozole is a meaningful advancement for these women."

"Since its accelerated approval in 2015, IBRANCE in combination with letrozole has become a standard of care for the treatment of post-menopausal women with ER+, HER2- advanced or metastatic breast cancer," said Hope Rugo, M.D., professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. "We now have seen consistent results across three randomized trials in which the addition of IBRANCE to an endocrine therapy significantly prolonged PFS compared to the endocrine therapy alone."

In the trial, median PFS for women treated with IBRANCE plus letrozole was 24.8 months (95% CI, 22.1-not estimable) compared with 14.5 months (95% CI, 12.9-17.1) for women treated with letrozole plus placebo (HR=0.58 [95% CI, 0.46-0.72], p<0.001), a 42% reduction in the risk of disease progression.

"IBRANCE has raised the bar for new treatments in hormone-receptor positive advanced breast cancer. The results of this Phase 3 trial add to the growing body of clinical data in support of IBRANCE and translates into hope for patients," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "We look forward to sharing the full PALOMA-2 data with global regulatory authorities with the goal of making IBRANCE available to more women around the world. Pfizer is proud of being a leader in the development of innovative therapies like IBRANCE that make a meaningful difference in patients’ lives."

Safety results were consistent with PALOMA-1 and no major unexpected safety findings were observed. The most common grade 3/4 adverse events with IBRANCE plus letrozole versus placebo plus letrozole were neutropenia (66.4% vs 1.4%), leukopenia (24.8% vs 0%), infections (6.5% vs 3.2%) and anemia (5.4% vs 1.8%). Febrile neutropenia was reported in 1.8% of patients in the IBRANCE plus letrozole group and none of the patients in the placebo plus letrozole group. For more information, please see Important Safety Information for IBRANCE below.2

IBRANCE first was approved by the U.S. Food and Drug Administration (FDA) in February 2015 and is indicated for the treatment of hormone receptor positive (HR+), HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.2 The indication in combination with letrozole was approved under accelerated approval based on PFS results from the Phase 2 PALOMA-1 study. As stated at the time of the approval, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the double-blind, Phase 3 PALOMA-2 study.2 A supplemental New Drug Application to support the conversion of the accelerated approval to regular approval based on the results of PALOMA-2 has been submitted to the FDA.

IBRANCE also is approved in the U.S. for the treatment of HR+, HER2-advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy based on results from the Phase 3 PALOMA-3 study.2

Since the initial approval in February 2015, more than 40,000 women have been prescribed IBRANCE by more than 8,500 prescribers in the U.S.

As previously disclosed, the European Commission has approved IBRANCE for the treatment of women with HR+, HER2- locally advanced or metastatic breast cancer. The approval is for IBRANCE to be used in combination with an aromatase inhibitor. The approval also covers the use of IBRANCE in combination with fulvestrant in women who have received prior endocrine therapy. In total, IBRANCE is approved in more than 50 countries.

About PALOMA-2

PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind Phase 3 study designed to assess the PFS of IBRANCE (125 mg orally once daily for three out of four weeks in repeated cycles) in combination with letrozole (2.5 mg once daily continuously) versus letrozole plus placebo as a first-line treatment for postmenopausal women with ER+, HER2- metastatic breast cancer. PALOMA-2 evaluated a total of 666 women from 186 global sites in 17 countries.

The full prescribing information for IBRANCE can be found at www.pfizer.com.

About IBRANCE (palbociclib) 125 mg capsules

IBRANCE is the first and only FDA approved oral inhibitor of CDKs 4 and 6,2 which are key regulators of the cell cycle that trigger cellular progression.3,4 In the U.S., IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.2 The indication in combination with letrozole is approved under accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, PALOMA-2.2

Important IBRANCE (palbociclib) Safety Information from the U.S. Prescribing Information

Neutropenia was the most frequently reported adverse reaction in PALOMA-1 (75%) and PALOMA-3 (83%). In PALOMA-1, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (56%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in about 1% of patients exposed to IBRANCE. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 14 of first 2 cycles, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Pulmonary embolism (PE) has been reported at a higher rate in patients treated with IBRANCE plus letrozole in PALOMA-1 (5%) and in patients treated with IBRANCE plus fulvestrant in PALOMA-3 (1%) compared with no cases in patients treated either with letrozole alone or fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat as medically appropriate.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-1 of IBRANCE plus letrozole vs letrozole alone included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-1 reported at a higher incidence in the IBRANCE plus letrozole group vs the letrozole alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE plus letrozole were pulmonary embolism (4%) and diarrhea (2%).

Lab abnormalities occurring in PALOMA-1 (all grades, IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs 26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs 35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs 16%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 of IBRANCE plus fulvestrant vs fulvestrant plus placebo included neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-3 reported at a higher incidence in the IBRANCE plus fulvestrant group vs the fulvestrant plus placebo group included neutropenia (66% vs 1%) and leukopenia (31% vs 2%). The most frequently reported serious adverse reactions in patients receiving IBRANCE plus fulvestrant were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in PALOMA-3 (all grades, IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), and decreased platelets (62% vs 10%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).