On March 16, 2016 Bristol-Myers Squibb Company (NYSE:BMY) reported that new clinical research data for two of its Immuno-Oncology medicines — Opdivo and Yervoy — will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting in New Orleans, LA, from April 16-20 (Press release, Bristol-Myers Squibb, MAR 16, 2016, View Source [SID:1234509597]).

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Data to be presented for Opdivo, as a single-agent and in combination with Yervoy, illustrate the company’s commitment to expanding its Immuno-Oncology research portfolio to include additional tumor types and developing treatment options that have the potential to extend survival in hard-to-treat cancers in broad patient populations.

Jean Viallet, M.D., Global Clinical Research Lead, Oncology, Bristol-Myers Squibb, commented, "At this year’s AACR (Free AACR Whitepaper), we are excited to present, for the first time, overall survival data from the first pivotal Phase 3 trial of an Immuno-Oncology agent, Opdivo, in previously treated squamous cell carcinoma of the head and neck, a cancer that has had very few treatment advances over the past ten years. These head and neck cancer data represent the fifth tumor type with overall survival data for Opdivo compared to a standard of care. We will also be presenting overall survival data from CheckMate -069, which was the first randomized trial to evaluate the Opdivo + Yervoy Regimen in the first-line setting for advanced melanoma, and has been a foundational study in building our scientific understanding of combining these two Immuno-Oncology agents to treat this form of cancer."

Key data presentations include:

CheckMate -141: New, pivotal phase 3 data evaluating Opdivo versus investigator’s choice for recurrent or metastatic head and neck squamous cell carcinoma (Late-Breaking and Clinical Trial Abstract #CT099) will be presented as an oral presentation during the Immuno-Oncology Clinical Trials II Plenary Session on Tuesday, April 19, 10:30 AM – 12:15 PM CT.
CheckMate -069: First presentation of overall survival rates from a randomized phase 2 trial evaluating the Opdivo + Yervoy combination in patients with advanced melanoma (Late-Breaking and Clinical Trial Abstract #CT002) will be presented as an oral presentation during the Immuno-Oncology Clinical Trials I Plenary Session on Sunday, April 17, 2016, 2:15 – 4:00 PM CT
The full set of data to be presented by Bristol-Myers Squibb includes:

Melanoma

Initial report of overall survival rates from a randomized phase 2 trial evaluating the combination of nivolumab and ipilimumab in patients with advanced melanoma
Author: M. Postow
Abstract #CT002
Oral Presentation, Immuno-Oncology Clinical Trials I Plenary Session
Sunday, April 17, 2016, 2:15 – 4:00 PM CT, La Nouvelle Ballroom, Morial Convention Center

Durable, long-term survival in previously treated patients with advanced melanoma who received nivolumab monotherapy in a phase 1 trial
Author: F. S. Hodi
Abstract #CT001
Oral Presentation, Immuno-Oncology Clinical Trials I Plenary Session
Sunday, April 17, 2016, 2:15 – 4:00 PM CT, La Nouvelle Ballroom, Morial Convention Center

Association of programmed death-ligand 1 (PD-L1) and 2 (PD-L2) expression with nivolumab efficacy in advanced melanoma
Author: S. J. Rodig
Abstract #CT133
Oral Presentation, Early Clinical Trials Evaluating Cell-based Checkpoint Inhibitors, and Novel Immunotherapeutics Minisymposium
Tuesday, April 19, 2016, 3:00 – 5:00 PM CT, Room 343, Morial Convention Center

Squamous Cell Carcinoma of the Head and Neck

Nivolumab versus investigator’s choice for recurrent or metastatic head and neck squamous cell carcinoma: CheckMate -141
Author: M. Gillison
Abstract #CT099
Oral Presentation, Immuno-Oncology Clinical Trials II Plenary Session
Tuesday, April 19, 2016, 10:30 AM – 12:15 PM CT, Room 391, Morial Convention Center
Lung Cancer

Impact of baseline serum cytokines on survival in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel: Exploratory analyses from CheckMate -063 and CheckMate -017
Author: B. Farsaci
Abstract #LB-072
Late-Breaking Minisymposium
Sunday, April 17, 2016, 4:15 – 6:15 PM CT, Room 275, Morial Convention Center

Characterization of the T-cell receptor repertoire in extensive disease small cell lung cancer
Author: Hussein
Abstract #4159
Poster Session, Immune Cell Activity Session
Tuesday, April 19, 2016, 1:00 – 5:00 PM CT, Convention Center, Halls G-J, Poster Section 31
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment choice alongside surgery, radiation, chemotherapy and targeted therapies for certain types of cancer.

We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. Our ongoing Immuno-Oncology clinical program is looking at broad patient populations, across multiple solid tumors and hematologic malignancies, and lines of therapy and histologies, with the intent of powering our trials for overall survival and other important measures like durability of response. We pioneered the research leading to the first regulatory approval for the combination of two Immuno-Oncology agents, and continue to study the role of combinations in cancer.

We are also investigating other immune system pathways in the treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1, GITR, CSF1R, IDO, and LAG-3. These pathways may lead to potential new treatment options – in combination or monotherapy – to help patients fight different types of cancers.

Our collaboration with academia, as well as small and large biotech companies, to research the potential of Immuno-Oncology and non-Immuno-Oncology combinations, helps achieve our goal of providing new treatment options in clinical practice.

At Bristol-Myers Squibb, we are committed to changing survival expectations in hard-to-treat cancers and the way patients live with cancer.

About Opdivo

Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells, and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s suppressive signaling on the immune system, including the interference with an anti-tumor immune response.

Opdivo’s broad global development program is based on Bristol-Myers Squibb’s understanding of the biology behind Immuno-Oncology. Our company is at the forefront of researching the potential of Immuno-Oncology to extend survival in hard-to-treat cancers. This scientific expertise serves as the basis for the Opdivo development program, which includes a broad range of Phase 3 clinical trials evaluating overall survival as the primary endpoint across a variety of tumor types. The Opdivo trials have also contributed toward the clinical and scientific understanding of the role of biomarkers and how patients may benefit from Opdivo across the continuum of PD-L1 expression. To date, the Opdivo clinical development program has enrolled more than 18,000 patients.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in 48 countries including the United States, Japan, and in the European Union.

INDICATIONS

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

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 confirmatory trials.

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.

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

Immune-mediated pneumonitis, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience with solid tumors, fatal immune-mediated pneumonitis occurred with OPDIVO. In addition, in Checkmate 069, there were six patients who died without resolution of abnormal respiratory findings. Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In Checkmate 069 and 067, immune-mediated pneumonitis occurred in 6% (25/407) of patients receiving OPDIVO with YERVOY: Fatal (n=1), Grade 3 (n=6), Grade 2 (n=17), and Grade 1 (n=1). In Checkmate 037, 066, and 067, immune-mediated pneumonitis occurred in 1.8% (14/787) of patients receiving OPDIVO: Grade 3 (n=2) and Grade 2 (n=12). In Checkmate 057, immune-mediated pneumonitis, including interstitial lung disease, occurred in 3.4% (10/287) of patients: Grade 3 (n=5), Grade 2 (n=2), and Grade 1 (n=3). In Checkmate 025, pneumonitis, including interstitial lung disease, occurred in 5% (21/406) of patients receiving OPDIVO and 18% (73/397) of patients receiving everolimus. Immune-mediated pneumonitis occurred in 4.4% (18/406) of patients receiving OPDIVO: Grade 4 (n=1), Grade 3 (n=4), Grade 2 (n=12), and Grade 1 (n=1).

Immune-Mediated Colitis

Immune-mediated colitis can occur with OPDIVO treatment. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon restarting OPDIVO. When administered with YERVOY, withhold OPDIVO for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis upon restarting OPDIVO. In Checkmate 069 and 067, diarrhea or colitis occurred in 56% (228/407) of patients receiving OPDIVO with YERVOY. Immune-mediated colitis occurred in 26% (107/407) of patients: Grade 4 (n=2), Grade 3 (n=60), Grade 2 (n=32), and Grade 1 (n=13). In Checkmate 037, 066, and 067, diarrhea or colitis occurred in 31% (242/787) of patients receiving OPDIVO. Immune-mediated colitis occurred in 4.1% (32/787) of patients: Grade 3 (n=20), Grade 2 (n=10), and Grade 1 (n=2). In Checkmate 057, diarrhea or colitis occurred in 17% (50/287) of patients receiving OPDIVO. Immune-mediated colitis occurred in 2.4% (7/287) of patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In Checkmate 025, diarrhea or colitis occurred in 25% (100/406) of patients receiving OPDIVO and 32% (126/397) of patients receiving everolimus. Immune-mediated diarrhea or colitis occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 3 (n=5), Grade 2 (n=7), and Grade 1 (n=1).

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

Immune-mediated hepatitis can occur with OPDIVO treatment. 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 Checkmate 069 and 067, immune-mediated hepatitis occurred in 13% (51/407) of patients receiving OPDIVO with YERVOY: Grade 4 (n=8), Grade 3 (n=37), Grade 2 (n=5), and Grade 1 (n=1). In Checkmate 037, 066, and 067, immune-mediated hepatitis occurred in 2.3% (18/787) of patients receiving OPDIVO: Grade 4 (n=3), Grade 3 (n=11), and Grade 2 (n=4). In Checkmate 057, one patient (0.3%) developed immune-mediated hepatitis. In Checkmate 025, there was an increased incidence of liver test abnormalities compared to baseline in AST (33% vs 39%), alkaline phosphatase (32% vs 32%), ALT (22% vs 31%), and total bilirubin (9% vs 3.5%) in the OPDIVO and everolimus arms, respectively. Immune-mediated hepatitis requiring systemic immunosuppression occurred in 1.5% (6/406) of patients receiving OPDIVO: Grade 3 (n=5) and Grade 2 (n=1).

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 Dermatitis

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 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

Hypophysitis, adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus can occur with OPDIVO treatment. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency during and after treatment, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer 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. Administer insulin for type 1 diabetes. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In Checkmate 069 and 067, hypophysitis occurred in 9% (36/407) of patients receiving OPDIVO with YERVOY: Grade 3 (n=8), Grade 2 (n=25), and Grade 1 (n=3). In Checkmate 037, 066, and 067, hypophysitis occurred in 0.9% (7/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=3), and Grade 1 (n=2). In Checkmate 025, hypophysitis occurred in 0.5% (2/406) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 1 (n=1). In Checkmate 069 and 067, adrenal insufficiency occurred in 5% (21/407) of patients receiving OPDIVO with YERVOY: Grade 4 (n=1), Grade 3 (n=7), Grade 2 (n=11), and Grade 1 (n=2). In Checkmate 037, 066, and 067, adrenal insufficiency occurred in 1% (8/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=5), and Grade 1 (n=1). In Checkmate 057, 0.3% (1/287) of OPDIVO-treated patients developed adrenal insufficiency. In Checkmate 025, adrenal insufficiency occurred in 2.0% (8/406) of patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=4), and Grade 1 (n=1). In Checkmate 069 and 067, hypothyroidism or thyroiditis occurred in 22% (89/407) of patients receiving OPDIVO with YERVOY: Grade 3 (n=6), Grade 2 (n=47), and Grade 1 (n=36). Hyperthyroidism occurred in 8% (34/407) of patients: Grade 3 (n=4), Grade 2 (n=17), and Grade 1 (n=13). In Checkmate 037, 066, and 067, hypothyroidism or thyroiditis occurred in 9% (73/787) of patients receiving OPDIVO: Grade 3 (n=1), Grade 2 (n=37), Grade 1 (n=35). Hyperthyroidism occurred in 4.4% (35/787) of patients receiving OPDIVO: Grade 3 (n=1), Grade 2 (n=12), and Grade 1 (n=22). In Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis, occurred in 7% (20/287) and elevated thyroid stimulating hormone occurred in 17% of patients receiving OPDIVO. Grade 1 or 2 hyperthyroidism occurred in 1.4% (4/287) of patients. In Checkmate 025, thyroid disease occurred in 11% (43/406) of patients receiving OPDIVO, including one Grade 3 event, and in 3.0% (12/397) of patients receiving everolimus. Hypothyroidism/thyroiditis occurred in 8% (33/406) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=17), and Grade 1 (n=14). Hyperthyroidism occurred in 2.5% (10/406) of patients receiving OPDIVO: Grade 2 (n=5) and Grade 1 (n=5). In Checkmate 069 and 067, diabetes mellitus or diabetic ketoacidosis occurred in 1.5% (6/407) of patients: Grade 4 (n=3), Grade 3 (n=1), Grade 2 (n=1), and Grade 1 (n=1). In Checkmate 037, 066, and 067, diabetes mellitus or diabetic ketoacidosis occurred in 0.8% (6/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=3), and Grade 1 (n=1). In Checkmate 025, hyperglycemic adverse events occurred in 9% (37/406) patients. Diabetes mellitus or diabetic ketoacidosis occurred in 1.5% (6/406) of patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=1).

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

Immune-mediated nephritis can occur with OPDIVO treatment. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 increased serum creatinine, withhold and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue. In Checkmate 069 and 067, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients: Grade 4 (n=4), Grade 3 (n=3), and Grade 2 (n=2). In Checkmate 037, 066, and 067, nephritis and renal dysfunction of any grade occurred in 5% (40/787) of patients receiving OPDIVO. Immune-mediated nephritis and renal dysfunction occurred in 0.8% (6/787) of patients: Grade 3 (n=4) and Grade 2 (n=2). In Checkmate 057, Grade 2 immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients receiving OPDIVO. In Checkmate 025, renal injury occurred in 7% (27/406) of patients receiving OPDIVO and 3.0% (12/397) of patients receiving everolimus. Immune-mediated nephritis and renal dysfunction occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 5 (n=1), Grade 4 (n=1), Grade 3 (n=5), and Grade 2 (n=6).

Immune-Mediated Rash

Immune-mediated rash can occur with OPDIVO treatment. Severe rash (including rare cases of fatal toxic epidermal necrolysis) occurred in the clinical program of OPDIVO. Monitor patients for rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4. In Checkmate 069 and 067, immune-mediated rash occurred in 22.6% (92/407) of patients receiving OPDIVO with YERVOY: Grade 3 (n=15), Grade 2 (n=31), and Grade 1 (n=46). In Checkmate 037, 066, and 067, immune-mediated rash occurred in 9% (72/787) of patients receiving OPDIVO: Grade 3 (n=7), Grade 2 (n=15), and Grade 1 (n=50). In Checkmate 057, immune-mediated rash occurred in 6% (17/287) of patients receiving OPDIVO including four Grade 3 cases. In Checkmate 025, rash occurred in 28% (112/406) of patients receiving OPDIVO and 36% (143/397) of patients receiving everolimus. Immune-mediated rash, defined as a rash treated with systemic or topical corticosteroids, occurred in 7% (30/406) of patients receiving OPDIVO: Grade 3 (n=4), Grade 2 (n=7), and Grade 1 (n=19).

Immune-Mediated Encephalitis

Immune-mediated encephalitis can occur with OPDIVO treatment. 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 Checkmate 067, encephalitis was identified in one patient (0.2%) receiving OPDIVO with YERVOY. In Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%) receiving OPDIVO.

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. In < 1.0% of patients receiving OPDIVO, the following clinically significant, immune-mediated adverse reactions occurred: uveitis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, and sarcoidosis. Across clinical trials of OPDIVO as a single agent administered at doses of 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

Severe infusion reactions have been reported in <1.0% of patients in clinical trials of OPDIVO. 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 Checkmate 069 and 067, infusion- related reactions occurred in 2.5% (10/407) of patients receiving OPDIVO with YERVOY: Grade 2 (n=6) and Grade 1 (n=4). In Checkmate 037, 066, and 067, Grade 2 infusion related reactions occurred in 2.7% (21/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=8), and Grade 1 (n=11). In Checkmate 057, Grade 2 infusion reactions requiring corticosteroids occurred in 1.0% (3/287) of patients receiving OPDIVO. In Checkmate 025, hypersensitivity/infusion-related reactions occurred in 6% (25/406) of patients receiving OPDIVO and 1.0% (4/397) of patients receiving everolimus.

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 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 relative to the OPDIVO arm. 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 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO. 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. 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 057, serious adverse reactions occurred in 47% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pulmonary embolism, dyspnea, pleural effusion, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia.

Common Adverse Reactions

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm 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 arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO vs dacarbazine were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 057, the most common adverse reactions (≥20%) reported with OPDIVO were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%), and constipation (23%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO vs everolimus 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 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%).

On March 16, 2016 Amrita Therapeutics ("the Company"), a biopharmaceutical company developing innovative technologies from the microbiome, reported that it is pleased to announce its submission to the FDA of a pre-INDType B Meeting request for discussion of development plans for the Company’s lead oncology peptide AT-01C (Press release, Amrita Therapeutics, MAR 16, 2016, View Source [SID:1234512730]).

Amrita Therapeutics’ AT-01C peptide demonstrates p53 ("guardian of the genome") tumor suppression and binds to the SMAR1* protein for down-regulation of oncogenes with little or no toxicity to healthy tissues, with effectiveness against solid tumors including genitourinary, gastrointestinal (GI), liver and CNS cancers. In parallel to clinical development of AT-01C, the Company is focusing on the ‘master regulator’ SMAR1 biomarker as a companion diagnostic test to identify patients most likely to benefit from AT-01C therapy.

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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

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Susan K. Finston, Amrita Therapeutics’ Chief Executive Officer notes, "we continue to gain insights into the extraordinary therapeutic potential of peptides from the microbiome and look forward to clinical development of AT-01C to address unmet needs of cancer patients."

With less toxicity and fewer side effects, naturally occurring peptide drugs have a greater likelihood of regulatory approval double that of small molecule new chemical entities (NCEs) for a range of indications including infectious diseases, metabolic disorders and advanced cancer therapies. Amrita’s first peptide drug has the potential to reach sales in excess of $ 1 billion within the first years of launch.

On March 16, 2016 Kite Pharma, Inc., (Nasdaq:KITE) ("Kite") a clinical-stage biopharmaceutical company focused on developing engineered autologous T cell therapy (eACT) products for the treatment of cancer, reported that two oral presentations and two poster presentations to be delivered at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana (Press release, Kite Pharma, MAR 16, 2016, View Source [SID:1234509601]). The oral presentations will address KTE-C19, Kite’s lead chimeric antigen receptor (CAR) product candidate, and, separately, an engineered T cell receptor (TCR) product candidate targeting the cancer testis antigen MAGE-A3. The TCR product candidate is currently being studied as part of a Cooperative Research and Development Agreement (CRADA) between Kite and the National Cancer Institute.

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Oral Presentations:

Title: Updated Phase 1 Results from ZUMA-1: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 (Anti-CD19 CAR T Cells) in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)

Date: Tuesday, April 19, 2016 3:00-5:00PM Central Time
Session: Early Clinical Trials Evaluating Cell-based, Checkpoint Inhibitors, and Novel Immunotherapeutics
Abstract Number: CT135
Location: Room 343, Morial Convention Center
Presenter: Armin Ghobadi, M.D., Washington University, St. Louis, MO

Title: A Phase 1 Study of an HLA-DPB1*0401-restricted T Cell Receptor Targeting MAGE-A3 for Patients with Metastatic Cancer

Date: Sunday, April 17, 2016 2:15-4:00PM Central Time
Session: Immuno-Oncology Clinical Trials I
Abstract Number: CT003
Location: La Nouvelle Ballroom, Morial Convention Center
Presenter: Yong-Chen W. Lu, Ph.D., Surgery Branch, National Cancer Institute

Poster Presentations:

Title: Manufacturing and Characterization of KTE-C19 in a Multicenter Trial of Subjects with Refractory Aggressive Non-Hodgkin’s Lymphoma (NHL) (ZUMA-1)

Date: Monday, April 18, 2016 1:00-5:00PM Central Time
Session: Adoptive Cell Therapy
Abstract Number: 2308
Location: Poster Hall, Section 25, Poster Board 20
Presenter: Marc Better, Ph.D., Kite Pharma, Santa Monica, CA

Title: Comparative Evaluation of Peripheral Blood T cells and Resultant Engineered Anti-CD19 CAR T Cell Products from Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL) Patients

Date: Monday, April 18, 2016 1:00-5:00PM Central Time
Session: Adoptive Cell Therapy
Abstract Number: 2305
Location: Poster Hall, Section 25, Poster Board 17
Presenter: Timothy J. Langer, Kite Pharma, Santa Monica, CA

About KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B cell malignancies. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation status to KTE-C19, for the treatment of patients with refractory diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, and transformed follicular lymphoma. KTE-C19 has also secured Orphan Drug Designation in the U.S. for DLBCL and in the EU for various hematological indications.

On March 16, 2016 GSK and Miltenyi Biotec reported a strategic collaboration that will bring together GSK’s expertise in developing cell and gene therapy based treatments with Miltenyi Biotec’s global leadership in cell processing and related technologies in cell therapy (Press release, GlaxoSmithKline, MAR 16, 2016, View Source [SID:1234509747]). The collaboration seeks to optimise the manufacture and delivery of these personalised therapies using increased automation and leading edge processing technology.

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

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GSK is building a cell and gene therapy R&D platform to underpin development of novel therapies in oncology and rare diseases – two of its core research areas. This reflects the company’s belief in cell and gene therapy’s potential as an important treatment approach for tackling the underlying cause of serious disease.

Through the collaboration, Miltenyi Biotec will engage with GSK to integrate greater automation and high-tech processing technology into GSK’s current cell and gene therapy R&D manufacturing capabilities. The goal is to use this increased automation to further industrialise cell and gene therapy, overcoming the manufacturing and scale-up constraints associated with current, more manual cell and gene therapy processes. This could reduce the costs and geographical barriers associated with this treatment approach, speed development of therapies and support their potential beyond rare diseases and limited populations.

The collaboration will also bring together the technology and expertise of both companies to advance the discovery of new CAR (chimeric antigen-receptor) T-cell based therapeutics – cells that have been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. GSK and Miltenyi Biotec will collaborate on defined CAR-T oncology targets and on the development of advancements in technologies in this space that may be further applied by both companies. This collaboration supplements GSK’s existing CAR-T preclinical portfolio.

Patrick Vallance, President of Pharmaceuticals R&D at GSK, said: "Cell based gene therapies are living treatments, unique to individual patients and complex to manufacture. We see tremendous potential for the cell and gene therapy platform we are building within GSK, however the complexity of current manufacturing processes limits their use to local treatment of small patient populations. Working with Miltenyi Biotec, our vision is to transform current technology so that we can expand the possibilities for cell and gene therapy treatment to wider patient populations with broader geographical reach."

Stefan Miltenyi, President and CEO at Miltenyi Biotec, said: "For more than 20 years we have been developing and providing cell therapy solutions to patients worldwide. Working together with the global experts at GSK, we will accelerate innovation to broaden patient access to future personalised cell and gene therapy."

About Cell and Gene therapies
Cell and gene therapies are potentially powerful disease modifying experimental treatments that focus on genetically engineering living cells to either repair the direct cause of a genetic defect or equip them with genes that enhance their functions.

To make cell and gene therapy treatments, selected populations of cells are extracted from the body and genetically-engineered to produce the desired therapeutic effect. This can mean replacing a faulty gene in a stem cell or changing immune cells so they can recognise tumours. The transformed cells are then re-introduced into a patient’s body where they exert their effect by replacing faulty genes or educating the immune system to recognise and kill cancer cells

On March 16, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH) ("Bio-Path"), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery technology to develop a portfolio of targeted nucleic acid cancer drugs, reported operational and financial results for the year ended December 31, 2015 (Filing, Annual, Bio-Path Holdings, 2015, MAR 16, 2016, View Source [SID:1234509584]).

"2015 was a year of significant progress for Bio-Path," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "With two full remissions achieved in the safety segment of our Phase II trial of lead candidate BP1001 in advanced AML patients, the formation of an inaugural Scientific Advisory Board, and receiving orphan drug designation for BP1001 in AML, we are looking forward to a successful 2016."

2015 Operational Highlights:

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· Finalized the data package for the monotherapy portion of the Phase I clinical trial of Bio-Path’s lead product candidate, BP1001 (Liposomal Grb2 antisense), in blood cancers during the fourth quarter of 2015. BP1001 was well tolerated and showed signs of anti-leukemia activity and no drug-related toxicities. Among 21 evaluable patients, more than half experienced at least a 50 percent reduction in peripheral or bone marrow blasts from baseline. Additionally, several patients demonstrated transient improvement and/or stable disease. Notably, one patient with chronic myelogenous leukemia (CML) blast phase showed a significant reduction in blasts. Patient data from the Phase I clinical trial also demonstrated significant reductions in the target Grb2 protein and its downstream proteins, providing positive evidence that Bio-Path’s DNAbilizeTM neutral lipid delivery with proprietary antisense technology successfully delivers an antisense drug substance to a diseased cell to knock down the target protein.

· Received orphan drug designation from the U.S. Food and Drug Administration (FDA) for BP1001 for the treatment of acute myeloid leukemia (AML) in the second quarter of 2015. Orphan drug status provides Bio-Path with seven years of exclusivity after receiving formal marketing approval, as well as additional development incentives.

· Performed preclinical testing of BP1001 in two additional indications—triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC), two cancers characterized by formation of aggressive tumors and relatively high mortality rates. Bio-Path is rolling this initiative into a broader solid tumor testing program, including advanced ovarian cancer. The preclinical program may be expanded to include combination therapy evaluations.

· Added a second drug manufacturer, strengthening Bio-Path’s manufacturing process while increasing capability and capacity.

· Continued preclinical evaluation of a third DNAbilizeTM product. Bio-Path’s product candidate screening and development program has validated the next promising candidate, which will diversify the Company’s product pipeline. Potential indications include diffuse large B-cell lymphoma, non-small cell lung cancer, pancreatic cancer and disease candidates outside of oncology, such as autoimmune disorders.

· Formed a Scientific Advisory Board to support the advancement of Bio-Path’s clinical and preclinical therapeutic candidates. Jorge Cortes, M.D., renowned leukemia expert from The University of Texas MD Anderson Cancer Center, joined as Chairman. Amy P. Sing, M.D., a member of Bio-Path’s board of directors and Senior Director of Medical Affairs at Genomic Health, Inc., joined as a founding member.

· Presented Bio-Path’s proprietary technology and clinical trial results at an international meeting. Jorge Cortes, M.D. of The University of Texas MD Anderson Cancer Center and Chair of Bio-Path’s Scientific Advisory Board presented a poster at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 7, 2015 in Orlando, FL. Dr. Cortes discussed data from the Phase I and safety segment of the Phase II clinical trials of BP1001 in blood cancers. These data included the complete remission of two evaluable patients receiving BP1001 in combination with low-dose cytarabine (LDAC) chemotherapy.

· Presented to the medical and scientific community at the IBC’s 17th Annual TIDES: Oligonucleotide and Peptide Therapeutics Conference in San Diego. The presentation featured Bio-Path’s DNAbilizeTM technology for delivering liposome/antisense drugs and highlighted BP1001. The TIDES Summit is prominently known as the premier conference for the oligonucleotide and peptide discovery, development and manufacturing industries.

· Continued enhancement of Bio-Path’s public profile within the investment community and biopharmaceutical industry. Chief Executive Officer Peter Nielsen delivered company presentations at the 17th Annual Rodman & Renshaw Global Investment Conference in September 2015, the 14th Annual BIO Investor Forum in October 2015, Biotech Showcase 2015 Conference in San Francisco, CA in January 2016 and the 18th Annual BIO CEO & Investor Conference in New York City in February 2016.

· Established an "at-the-market" ("ATM") program during the second quarter of 2015, through which it may offer and sell up to $25 million of common stock from time to time, at Bio-Path’s discretion, through an investment banker, acting as sales agent. Sales of Bio-Path common stock under the ATM program may be made directly on or through the Nasdaq Capital Market, among other methods. As of December 31, 2015, the Company has not offered or sold any shares of common stock under the ATM program.

Recent / First Quarter 2016 Operational Highlights:

· Completed the safety segment of the Phase II clinical trial of BP1001, in combination with low-dose cytarabine (LDAC) chemotherapy, in patients with advanced AML. Of the six evaluable patients, two had a complete response and two had a partial response, with one patient continuing treatment. Bio-Path saw no adverse events attributable to BP1001 treatment.

· Entered into a sponsored research agreement with The University of Texas MD Anderson Cancer Center to evaluate Bio-Path’s clinical pipeline for its ability to modulate pancreatic cancer.

Expected Upcoming Milestones:

· BP1001 in Acute Myeloid Leukemia (AML): Bio-Path is finalizing steps to commence a multi-site Phase II clinical trial assessing the efficacy of BP1001 in combination with low-dose cytarabine (LDAC) chemotherapy, which is expected to commence in the second quarter of 2016.

· BP1001 in Chronic Myelogenous Leukemia (CML): Bio-Path commenced development of a protocol for a Phase II clinical trial evaluating BP1001 in combination with frontline chemotherapy in CML patients in blast crisis, an area of unmet medical need. This clinical trial is expected to start in the second quarter of 2016.

· BP1002 (Liposomal Bcl2; L-Bcl2): Bio-Path is finalizing a preclinical package of toxicity, tissue distribution, pharmacokinetics and efficacy studies for its second product candidate, BP1002. An Investigational New Drug (IND) application will be filed with the FDA upon finalizing drug batch required for the Chemistry, Manufacturing and Controls section of the IND. Bio-Path expects that the favorable toxicity profile of BP1001 will allow for a Phase I clinical trial of BP1002 to begin at a higher dose, thus reducing the number of patients required to complete the safety phase of the trial.

2015 Financial Highlights:

· Bio-Path reported a net loss of $5.5 million for the year ended December 31, 2015, compared to a net loss of $4.5 million for the year ended December 31, 2014. The increase was primarily due to increased clinical trial expenses, manufacturing development, preclinical study costs and personnel costs associated with the addition of research and development support staff in the second half of 2014. The Company reported a net loss of $0.06 per share for the year ended December 31, 2015, compared to a net loss of $0.05 per share for the year ended December 31, 2014.

· Research and development expenses for the year ended December 31, 2015 increased to $3.0 million, compared to $1.8 million for the year ended December 31, 2014.

· General and administrative expenses for the year ended December 31, 2015 decreased to $2.5 million, compared to $2.7 million for the year ended December 31, 2014.

· As of December 31, 2015, the Company had a cash balance of $8.9 million, compared to $13.9 million at December 31, 2014. Net cash used in operating activities for the year ended December 31, 2015 was $5.0 million, compared to $3.8 million for the comparable period in 2014.

About Bio-Path’s Delivery Technology

Bio-Path’s drug delivery technology, called DNAbilize, involves microscopic-sized liposome particles that distribute nucleic acid drugs systemically and safely throughout the human body, via simple intravenous infusion. The delivery technology is applied to proprietary, single stranded (antisense) nucleic acid compounds with the potential to revolutionize the treatment of cancer and other diseases where druggable targets of disease are well characterized. The Company is currently focused on developing liposomal antisense drug candidates. Bio-Path also anticipates developing liposome tumor targeting technology, representing next-generation enhancements to the Company’s core liposome delivery technology.

About BP1001 (Liposomal Grb2 antisense)

BP1001 (Liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb2 protein expression. The protein Grb2 is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb2 should interrupt its vital signaling function and have a therapeutic application in cancer.