On April 05, 2016 Oasmia Pharmaceutical AB (NASDAQ: OASM), a developer of a new generation of drugs within human and veterinary oncology, reported the results of a study in healthy volunteers for the Company’s XR17 nanotechnology that it believes indicates the excipient’s vast potential across many pharmaceutical indications beyond the cytostatic drug market (Press release, Oasmia, APR 5, 2016, View Source [SID:1234510423]).

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The Company recently completed a single center, randomized, single-blind, placebo-controlled study to assess the pharmacokinetics, safety and tolerability of XR17 and XMeNa, one of the components of XR17, after performing single ascending doses in 48 healthy subjects. XR17 has been used in several previously conducted clinical trials without any adverse events connected to the substance, a result that now has been confirmed and reinforced by this study.

XR17 is Oasmia’s proprietary excipient, transforming novel or existing un-soluble molecules into water soluble nanoparticle formations which instantly is released in the blood stream without added solvent, resulting in shorter infusion time and no pre-medication for the patient. This innovative approach also allows for multiple cytostatics to be given in a single infusion, as opposed to a traditional process that would usually require two or more infusions. XR17 is the excipient of Oasmia’s human oncology treatment compound Paclical, as well as Oasmia’s formulation of doxorubicin for veterinary use, Doxophos Vet and Paccal Vet.

Oasmia believes this clinical breakthrough presents a tremendous opportunity to create revenue streams in addition to the development and commercial sales of its human and animal oncology treatments. The confirmation of XR17 as a drug delivery system creates the potential for licensing and deployment opportunities in additional therapeutics outside of the oncology treatment sector. A 2014 report estimated that "70% of molecules in the developmental pipeline are believed to be poorly soluble and 40% of already approved drugs are poorly soluble," creating what Oasmia believes is a market opportunity that can be fulfilled by XR17.

"The drug discovery program is often limited by poor solubility that in many cases can exclude the patients from highly potent medications and result in additional and expensive administrations. In worst cases, drugs that have shown strong potential in animal models may not be used as a pharmaceutical treatment due to solubility problems," said Margareta Eriksson, Vice President of Clinical Development at Oasmia Pharmaceutical. "We are pleased that this clinical study yielded the results we had anticipated, and consider it the first step in positioning XR17 as a drug delivery system with expansive potential in the pharmaceutical industry."

"The results of this clinical study present a tremendous market opportunity for Oasmia, one that we seek to capitalize on for future revenue potential," said Julian Aleksov, Executive Chairman of Oasmia. "XR17 has thus far fulfilled our expectations, clearly demonstrating that its potential for widespread adoption by the pharmaceutical sector is no longer exclusive to oncology, but all treatments. We believe this breakthrough and subsequent development will create a revenue channel for Oasmia in addition to the sales efforts of our family of commercialized and next-generation oncology products."

On April 5, 2016 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and MedImmune, the global biologics research and development arm of AstraZeneca (LSE: AZN, SSE: AZN, NYSE: AZN), reported that they have entered into a licensing agreement under which Regeneron will use MedImmune’s pyrrolobenzodiazepine (PBD)-based warhead and linker technology to produce antibodydrug conjugates (ADCs) as potential cancer treatments (Press release, Regeneron, APR 5, 2016, View Source [SID:1234510419]).

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Regeneron will have exclusive rights to utilize MedImmune’s proprietary PBD technology to develop ADCs against a number of cancer targets. MedImmune will receive an upfront payment, development and commercial milestone payments, as well as single-digit royalties on net sales of such products. MedImmune has the option to develop and commercialize certain products created with this technology in territories outside of the United States.

"Developing next generation antibody-drug conjugates, including our proprietary PBD technology, is one of our key strategic platforms in advancing cancer therapies. Today’s collaboration represents our third partnership in this area, as we look to grow our ADC portfolio both internally and externally," said Ronald Herbst, Vice President, Oncology Research & Development, MedImmune. "We are pleased to be working with Regeneron, a company that is committed to advancing scientific innovation in cancer treatments. Regeneron’s research capabilities complements our commitment to discovering and developing the next generation of cancer therapies."

ADCs are a promising area of cancer drug technology which may help enable the selective killing of cancer cells by combining a cytotoxic agent, or "warhead", with specific cancertargeting antibodies. MedImmune is committed to advancing its pre-clinical and clinical stage ADC portfolio, in addition to its focus in immuno-oncology.

"We believe the most successful approaches to cancer R&D will combine multiple innovative therapies and technologies, and therefore we are pursuing a diverse array of strategies, pathways and modalities including ADCs, bispecific antibodies and monocolonal antibodies," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "This new agreement will further bolster our efforts to advance new, effective treatment options for cancer patients in need."

Regeneron’s clinical pipeline in oncology includes a PD-1 checkpoint inhibitor antibody, which is being developed in collaboration with Sanofi, and a CD20xCD3 bispecific antibody. Regeneron expects to advance multiple additional candidates into human clinical trials over the next 12 to 24 months.

MedImmune’s PBD technology was invented and developed by Spirogen, a company acquired by MedImmune in 2013.

On April 5, 2016 Merck and Pfizer (NYSE:PFE) reported the treatment of the first patient in a Phase III study of avelumab*, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in an advanced renal cell carcinoma (RCC) setting (Press release, Pfizer, APR 5, 2016, View Source [SID:1234510394]).

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The study, JAVELIN Renal 101, is the first pivotal trial investigating avelumab in combination with INLYTA (axitinib), a tyrosine kinase inhibitor (TKI), in patients with previously untreated advanced RCC, and the only Phase III trial currently evaluating an anti-PD-L1 immunotherapy in combination with a vascular endothelial growth factor (VEGF)-receptor TKI in this setting. The 5-year survival rate for patients with distant metastatic RCC is approximately 12 percent.1

"Pfizer has a strong heritage in the treatment of metastatic RCC, and through the strategic alliance with Merck, we aim to further accelerate the development of potential therapies to help improve the lives of patients living with this disease," said Chris Boshoff, M.D., PhD., Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology. "As renal cell carcinoma is an immunogenic type of tumor that can respond to immunotherapy and to anti-angiogenic treatment, there is a strong scientific rationale for combining avelumab with INLYTA and we believe that this combination may help improve outcomes for patients with this cancer."

JAVELIN Renal 101 is a multicenter, international, randomized (1:1), open-label Phase III trial designed to evaluate the potential superiority, assessed by the progression-free survival (PFS), of first-line avelumab combined with INLYTA compared with SUTENT(sunitinib malate) monotherapy, an oral, small-molecule, multi-targeted receptor TKI, in patients with unresectable, locally advanced or metastatic RCC with clear cell component. The study will enroll 583 patients across approximately 170 sites in Asia, Europe, Latin America and North America.

"The first patient receiving treatment in this pivotal trial marks an important milestone in the strategic immuno-oncology alliance between Merck and Pfizer," said Alise Reicin, M.D., Head of Global Clinical Development at the biopharma business of Merck. "As part of the JAVELIN clinical development program, we are exploring the potential of innovative, rational combination therapies, which combine avelumab with other treatment modalities to address significant unmet needs that exist in challenging cancers, such as advanced renal cell carcinoma."

The clinical development program for avelumab now includes more than 1,600 patients who have been treated across more than 15 tumor types.

INLYTA is currently approved in the United States for the treatment of advanced RCC after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency for use in the European Union in adult patients with advanced RCC after failure of prior treatment with SUTENT or a cytokine. Following its approval in 2012, INLYTA has become a standard of care for second-line advanced RCC and has been used by an estimated 12,000 metastatic renal cell carcinoma patients in the United States.2 INLYTA is under investigation in combination with avelumab for the indication studied in this Phase III trial.

*Avelumab is the proposed International Non-proprietary Name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

About Renal Cell Carcinoma

Renal cell carcinoma accounts globally for 2-3% of all malignancies.3 As of 2012, more than 338,000 new cases of kidney cancer were diagnosed per year worldwide.4 In general, higher incidence rates of renal cell carcinoma occur in Eastern Asia, North America and Central/Eastern Europe.5 Early-stage renal cancers tend to have a better prognosis, compared with advanced/metastatic renal cancers.6

The five-year survival rate for localized kidney and renal pelvis cancer is approximately 90%.1 The five-year overall survival rate for patients with distant metastatic RCC is approximately 12%.1

In the past 7 years, major advances have been made in the improvement of clinical outcomes with the introduction of new therapies.7 The introduction of these therapies has extended median survival rates for metastatic renal cell carcinoma.7

About Avelumab

Avelumab (also known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

About INLYTA (axitinib)

INLYTA is indicated for the treatment of advanced RCC after failure of one prior systemic therapy. INLYTA, a kinase inhibitor, is an oral therapy that is designed to inhibit tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; these receptors can influence tumor growth, vascular angiogenesis and progression of cancer (the spread of tumors).

Selected Safety Information for INLYTA (axitinib)

Hypertension including hypertensive crisis has been observed. Blood pressure should be well-controlled prior to initiating INLYTA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. Discontinue INLYTA if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis.

Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk for these events.

Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose.

Cardiac failure has been observed and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. Management of cardiac failure may require permanent discontinuation of INLYTA.

Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment.

Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA.

No formal studies of the effect of INLYTA on wound healing have been conducted. Stop INLYTA at least 24 hours prior to scheduled surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed. If signs or symptoms occur, permanently discontinue treatment.

Monitor for proteinuria before initiation of, and periodically throughout, treatment. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment.

Liver enzyme elevation has been observed during treatment with INLYTA. Monitor ALT, AST and bilirubin before initiation of, and periodically throughout, treatment.

For patients with moderate hepatic impairment, the starting dose should be decreased. INLYTA has not been studied in patients with severe hepatic impairment.

Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant while receiving INLYTA.

The most common (≥20%) adverse reactions are diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation.

The most common (≥20%) lab abnormalities occurring in patients receiving INLYTA (all grades, vs sorafenib) included increased creatinine, decreased bicarbonate, hypocalcemia, decreased hemoglobin, decreased lymphocytes (absolute), increased ALP, hyperglycemia, increased lipase, increased amylase, increased ALT, and increased AST.

INLYTA is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

For more information on INLYTA and Pfizer Oncology, including Full Prescribing Information, please visit www.pfizer.com.

About SUTENT (sunitinib malate)

SUTENT is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. SUTENT was approved in 2006 and is indicated for the treatment of advanced/metastatic renal cell carcinoma.

Selected Safety Information for SUTENT (sunitinib malate)

Boxed Warning/Hepatotoxicity: Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.

Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant.

Given the potential for serious adverse reactions (ARs) in nursing infants, a decision should be made whether to discontinue nursing or SUTENT.

Cardiovascular events, including heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction, some of which were fatal, have been reported. Use SUTENT with caution in patients who are at risk for, or who have a history of, these events. Monitor patients for signs and symptoms of congestive heart failure (CHF) and, in the presence of clinical manifestations, discontinuation is recommended. Patients who presented with cardiac events, pulmonary embolism, or cerebrovascular events within the previous 12 months were excluded from clinical studies.

SUTENT has been shown to prolong QT interval in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias including Torsades de Pointes, which has been seen in <0.1% of patients. Monitoring with on-treatment electrocardiograms and electrolytes should be considered.

Hypertension may occur. Monitor blood pressure and treat as needed with standard antihypertensive therapy. In cases of severe hypertension, temporary suspension of SUTENT is recommended until hypertension is controlled.

There have been (<1%) reports, some fatal, of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS).

Hemorrhagic events, including tumor-related hemorrhage such as pulmonary hemorrhage, have occurred. Some of these events were fatal. Perform serial complete blood counts (CBCs) and physical examinations.

Cases of Tumor Lysis Syndrome (TLS) have been reported primarily in patients with high tumor burden. Monitor these patients closely and treat as clinically indicated.

Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, sometimes leading to renal failure or a fatal outcome, has been reported in patients who received SUTENT as monotherapy and in combination with bevacizumab. Discontinue SUTENT in patients developing TMA. Reversal of the effects of TMA has been observed after treatment was discontinued.

Proteinuria and nephrotic syndrome have been reported. Some of these cases have resulted in renal failure and fatal outcomes. Perform baseline and periodic urinalysis during treatment, with follow-up measurement of 24-hour urine protein as clinically indicated. Interrupt SUTENT and dose-reduce if 24-hour urine protein is ≥3 g; discontinue SUTENT in cases of nephrotic syndrome or repeat episodes of urine protein ≥3 g despite dose reductions.

Severe cutaneous reactions have been reported, including cases of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), some of which were fatal. If signs or symptoms of EM, SJS, or TEN are present, SUTENT treatment should be discontinued. If a diagnosis of SJS or TEN is suspected, treatment must not be re-started. Necrotizing fasciitis, including fatal cases, has been reported, including of the perineum and secondary to fistula formation. Discontinue SUTENT in patients who develop necrotizing fasciitis.

SUTENT has been associated with symptomatic hypoglycemia, which may result in loss of consciousness or require hospitalization. Reductions in blood glucose levels may be worse in patients with diabetes. Check blood glucose levels regularly during and after discontinuation of SUTENT. Assess whether antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

The most common adverse reactions (≥20%) are fatigue, asthenia, fever, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, hand-foot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, and bleeding.

For more information on SUTENT and Pfizer Oncology, including Full Prescribing Information, including Boxed warning, please visit www.pfizer.com.

On April 05, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, and Merck & Co., Inc. (NYSE:MRK), reported that they have completed the first two dose-escalation cohorts and launched the third dose-escalation cohort in their KEYNOTE-046 clinical trial (Press release, Advaxis, APR 5, 2016, View Source [SID:1234510393]).

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The Phase 1/2 study is evaluating the combination of ADXS-PSA (ADXS31-142) and KEYTRUDA (pembrolizumab), the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States, in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC).

The KEYNOTE-046 trial is the first-in-human study of Advaxis’ Lm immunotherapy candidate for prostate cancer. It is the second study initiated to evaluate the use of KEYTRUDA in the treatment of advanced prostate cancer.

"We are one step closer to evaluating our Lm platform in combination with a PD-1 antibody and are excited to launch this next cohort," said Daniel J. O’Connor, President and Chief Executive Officer at Advaxis. "We are thrilled to continue our collaboration with Merck in pursuit of finding a treatment option for a form of prostate cancer where few options exist."

KEYNOTE-046 is a multicenter, dose determining, open-label Phase 1/2 study designed to evaluate the safety and efficacy of ADXS-PSA as a monotherapy and in combination with KEYTRUDA in 51 mCRPC patients. Part A of the study is a dose escalating study designed to establish the maximum tolerated dose of ADXS-PSA as a monotherapy. Part B of the study will commence mid-year and evaluate ADXS-PSA in combination with KEYTRUDA, followed by an expansion cohort phase. The primary objective is to evaluate the safety and tolerability of the two immunotherapies, with the secondary objective to evaluate anti-tumor activity and progression-free survival.

The companies plan to submit an abstract to a major medical meeting on the dose-escalation portion of the study in the second half of the year. Further information about KEYNOTE-046 can be found on ClinicalTrials.gov, using Identifier NCT02325557.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that approximately 180,890 new cases of prostate cancer will be diagnosed and about 26,120 men are expected to die of the disease this year.

About ADXS-PSA

ADXS-PSA is an Lm Technology product candidate that is a multi-function immunotherapy designed to target prostate cancer. ADXS-PSA combines potent innate immune stimulation, triggering of STING receptors, and induction of T-cell response targeting prostate specific antigen (PSA) with tumor microenvironment effects. In a preclinical analysis this approach also inhibits the Treg and myeloid-derived suppressor cells (MDSCs) that contribute to immunologic tolerance of prostate cancer. Preclinical studies have shown ADXS constructs to be synergistic with checkpoint inhibitors like Keytruda.

About KEYTRUDA (pembrolizumab)

KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merck is advancing a broad and fast-growing clinical development program for KEYTRUDA with more than 70 clinical trials – across more than 30 tumor types and over 8,000 patients – both as a monotherapy and in combination with other therapies.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma receiving KEYTRUDA (the approved indication in the United States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.

Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.

Other clinically important immune-mediated adverse reactions can occur. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic neuritis, and rhabdomyolysis.

For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

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

For the treatment of advanced melanoma, KEYTRUDA was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied. Serious adverse reactions occurred in 36% of patients receiving KEYTRUDA. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in ≥20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at View Source and the Medication Guide for KEYTRUDA at View Source

On April 5, 2016 Bellicum Pharmaceuticals Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported the presentation of interim data from the lead site in Bellicum’s ongoing BP-004 Phase 1/2 clinical trial during the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Valencia, Spain (Press release, Bellicum Pharmaceuticals, APR 5, 2016, View Source [SID:1234510391]).

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Studies with BPX-501 were selected for two oral presentations, including one during the Presidential Symposium session where significant findings from the meeting are featured.

In the ongoing BP-004 clinical trial, malignant and nonmalignant pediatric patients receive a haploidentical, T cell-depleted hematopoietic stem cell transplant (HSCT) followed by an add-back of BPX-501 donor T cells. The trial is designed to evaluate whether this regimen is safe and improves immune reconstitution, infection control and overall outcomes.

In an oral presentation reviewing the preliminary outcomes from the BP-004 clinical trial in 17 high-risk pediatric patients with blood cancers, the data showed that BPX-501 cells expand in vivo and persist over time, contributing to adaptive immunity. There was no transplant-related mortality due to infections, GvHD or other transplant-related complications. Additionally, the relapse rate to date compares favorably with that of historical controls, with 16 of 17 patients in the trial with acute leukemias showing disease-free outcomes. The median follow-up period to date for these patients was approximately seven months.

In a feature presentation during the Presidential Symposium session, initial outcomes for nonmalignant patients were reviewed. The data included children with genetic diseases including Fanconi anemia (5), beta thalassemia major (5), severe combined immunodeficiency (SCID or "bubble boy" disease) (5), Wiskott-Aldrich Syndrome (4) and other orphan diseases (5). All 24 children treated remain disease-free with no treatment-related mortality (median follow-up period of approximately seven months), consistent with earlier results presented at ASH (Free ASH Whitepaper) 2015.

"These interim results continue to be very encouraging and indicate that a haploidentical transplant, with the addition of BPX-501-modified donor T cells, can be an attractive option for children in need of a transplant," said lead investigator Dr. Franco Locatelli, Director, Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome. "Future studies will address the role of repeated infusions or higher numbers of BPX-501 cells in malignant patients with resistant disease."

"In both malignant and nonmalignant patients, the results show that treatment with BPX-501 appears safe, well-tolerated, and provides important immune benefits," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "These data also demonstrate high BPX-501 cell viability, expansion and persistence, and that the improvement of immune reconstitution is sustained. We look forward to sharing more results as these data mature, and providing updates following our plan to meet with the U.S. FDA and EMA during the second quarter of this year."

A copy of the slides presented at the meeting is available in the Events & Presentations section of bellicum.com.

About BPX-501

BPX-501 is an adjunct T cell therapy of genetically modified donor T cells incorporating Bellicum’s proprietary CaspaCIDe safety switch. The product candidate is designed to provide a safety net to eliminate the BPX-501 alloreactive T cells should severe GvHD occur, enabling physicians to more safely perform haploidentical stem cell transplants by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

BP-004 Clinical Trial Design

In December 2014, Bellicum initiated BP-004, a Phase 1/2 clinical trial in children with leukemias, lymphomas, or orphan inherited blood disorders, such as severe combined immunodeficiency (SCID), Wiskott-Aldrich Syndrome, beta thalassemia and sickle cell disease, all chronic life-long disorders for which HSCT is curative. The trial is being conducted in both European and U.S. pediatric transplant centers and plans to enroll up to 90 patients. The open label dose escalation trial is evaluating whether BPX-501 T cells from a haploidentical donor, typically the child’s mother or father, administered following a T-depleted HSCT, are safe and can enhance immune reconstitution.