On September 9, 2015 Genmab A/S (OMX: GEN) reported that Janssen-Cilag International NV (Janssen) has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for daratumumab (Press release, Genmab, SEP 9, 2015, View Source [SID:1234507428]). The submission is for daratumumab as a treatment for patients with multiple myeloma who have received at least three different lines of therapy including both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD.

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The submission triggers a milestone payment of USD 10 million to Genmab from Janssen. The milestone was included in Genmab’s financial guidance for 2015. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

This submission in Europe follows the completion of the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in July this year. Both regulatory submissions include data from the Phase II study (Sirius MMY2002) of daratumumab in multiple myeloma patients who have received at least three prior lines of therapy including both a PI and an IMiD, or who are double refractory to a PI and an IMiD. However, safety and efficacy data from the Phase I/II study (GEN501) and safety data from three other studies have also been included in the submission.

"The submission of the European regulatory application for daratumumab is another significant milestone in the development of daratumumab. We have seen very promising clinical data and believe daratumumab could provide an important new treatment alternative for multiple myeloma patients if approved," said Jan van de Winkel, Ph.D, Chief Executive Officer of Genmab.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 124,225 people will be diagnosed and 87,084 will die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including PIs or IMiDs, have poor prognoses and few treatment options.6

About daratumumab
Daratumumab is an investigational human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It induces rapid tumor cell death through multiple immune-mediated mechanisms7, including complement-dependent cytotoxicity7, antibody-dependent cellular phagocytosis8 and antibody-dependent cellular cytotoxicity7, as well as via induction of apoptosis9 . Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the US FDA.

On September 9, 2015 Celsion Corporation (NASDAQ: CLSN), a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases, reported that the Company has completed the integration of its June 2014 acquisition of EGEN, Inc. and has provided an update on its clinical development plans for GEN-1, the Company’s DNA-based immunotherapy for the localized treatment of ovarian and brain cancer (Press release, Celsion, SEP 9, 2015, View Source [SID:1234507427]).

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Following the acquisition of EGEN, Celsion has consolidated all early stage and preclinical assets at its Huntsville, AL facility. All clinical development, commercialization (including its Early Access Programs for ThermoDox), business development and administrative functions are now located in Lawrenceville, NJ. From this reorganization, Celsion expects to realize a 15 to 20 percent reduction in personnel and related annual operational costs.

Additionally, the Company has evaluated opportunities to maximize efficiency in its GEN-1 IL-12-based immunotherapy and has structured its clinical development program to capitalize on previously established proof-of-concept clinical data. GEN-1 has demonstrated promising clinical activity and tolerability in platinum-resistant and recurrent ovarian cancer patients, as well as synergistic anti-cancer effects in combination with bevacizumab (Avastin) in preclinical models.

The Company’s OVATION Study, a Phase 1b dose escalating trial combining GEN-1 with neo-adjuvant therapies in newly diagnosed ovarian cancer patients, is expected to commence enrollment in the second half of 2015. The first OVATION site at the University of Alabama at Birmingham has been initiated, with three additional sites expected to follow shortly. Data from this open label study is expected in the fourth quarter of 2015, and will continue into the first half of next year at higher doses of GEN-1. This trial will provide a starting dose for a follow-on Phase I/II study combining GEN-1 with Avastin and Doxil.

The Company also expects to commence a second ovarian cancer development program with initiation of a Phase I/II dose escalating trial evaluating GEN-1 in combination with Avastin and Doxil in platinum-resistant ovarian cancer patients later this year. This new combination study in platinum-resistant ovarian cancer is supported by two preclinical studies demonstrating that the combination of GEN-1 with Avastin may result in significant clinical benefit with a favorable safety profile, as well as a prior Phase 1b trial of GEN-1 plus Doxil in platinum resistant breast cancer patients.

The Company is now completing a comprehensive series of pre-clinical safety and efficacy studies, and plans to initiate a third Phase I trial combining GEN-1 with current standard of care to treat newly resected glioblastoma multiforme (GBM) brain cancer patients in 2016.

"Over the past 12 months, since our acquisition of EGEN, Inc., we have carefully evaluated our current organizational structure and collective management competencies to determine the most efficient path forward for our broad, diversified product pipeline. Our new organization will be both lean and focused on generating clinical data from our GEN-1 platform," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "As an IL-12 immunotherapy, GEN-1 has broad potential in multiple tumor types, and our clinical strategy is designed to accelerate its development, establish its clinical utility in various indications and drive it toward the market."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer. GEN-1 has also demonstrated preclinical activity in glioblastoma multiforme (brain cancer) and the Company plans to initiate a Phase I study in this indication in the second half of 2015.

About Celsion Corporation

On September 9, 2015 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the initiation of a Phase 1/2 clinical study that will investigate the use of TGR-1202, the Company’s oral PI3K delta inhibitor and TG-1101 (ublituximab), the Company’s glycoengineered anti-CD20 monoclonal antibody in combination with pembrolizumab the anti-PD-1 immune checkpoint inhibitor, in patients with relapsed or refractory CLL (Press release, TG Therapeutics, SEP 9, 2015, View Source [SID:1234507426]). This will be the first clinical trial evaluating the safety, tolerability and effectiveness of the triple combination of a PI3K delta inhibitor with an anti-CD20 mAb and an anti-PD-1 checkpoint inhibitor.

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"We are very excited about the launch of this combination study and its potential in treating patients with CLL. To date, engaging T-cells to fight CLL has been promising but has yet to produce the dramatic effects seen in other settings. We believe our proprietary TG-1101 plus TGR-1202 regimen in combination with T-cell enhancing therapies, like anti-PD-1, could significantly improve the outcomes for patients with CLL," stated Michael S. Weiss, the Company’s Executive Chairman and Interim Chief Executive Officer. Mr. Weiss continued, "Additionally, with our own anti-PD-L1 antibody expected to enter clinical trials next year, this trial will give us a nice head start in designing our proprietary combination clinical program."

Dr. Anthony Mato, an assistant professor in the Perelman School of Medicine at the University of Pennsylvania, Director of the Center for CLL at Penn’s Abramson Cancer Center and Study Chair of the Phase 1/2 study added, "We look forward to collaborating with TG Therapeutics on this novel combination clinical trial. Our center has been intimately involved with T-cell therapies for hematologic diseases and we are firm believers in the promise they hold broadly for cancer patients. The combination of TG-1101 and TGR-1202 has demonstrated unique tolerability and activity which we believe represents a strong backbone on which to add additional novel therapies. We believe the novel approach utilized in this study, where we will induce a response with TG-1101 and TGR-1202, followed by consolidation with anti-PD-1 therapy, could maximize the potential benefit of T-cell therapy in CLL. We are thrilled to have moved this study from concept to first patient enrolled in just a few months, and look forward to offering patients with advanced CLL new options with this novel triple combination."

The Phase 1 part of the study will evaluate the safety, tolerability, and appropriate dose of pembrolizumab when combined with TGR-1202 and TG-1101 in patients with advanced CLL. The Phase 2 part of the study will further evaluate the safety and effectiveness of the triple combination at the recommended Phase 2 dose.

This study is currently open to enrollment at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, PA. More information on this clinical study can be found at www.clinicaltrials.gov.

On September 9, 2015 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the company and its collaborator, Takeda Pharmaceutical Company Limited (Takeda), completed patient enrollment in the phase 3 ALCANZA clinical trial (Press release, Seattle Genetics, SEP 9, 2015, View Source [SID:1234507425]). ALCANZA is a randomized trial evaluating ADCETRIS (brentuximab vedotin) versus investigator’s choice of methotrexate or bexarotene in 132 patients with CD30-expressing cutaneous T-cell lymphoma (CTCL) who received prior systemic therapy.

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ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on skin lesions in at least 50 percent of patients with CTCL. The ALCANZA trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA). In addition, Takeda received European Medicines Agency (EMA) scientific advice. In 2012, the FDA granted ADCETRIS orphan drug designation for the treatment of mycosis fungoides (MF), which is the most common type of CTCL. ADCETRIS is currently not approved for the treatment of CTCL.

Data from two investigator-sponsored phase 2 clinical trials evaluating ADCETRIS in relapsed CTCL were recently published in the Journal of Clinical Oncology (JCO) by physicians at Stanford University and the University of Texas MD Anderson Cancer Center. The results of these two clinical trials demonstrated objective response rates of 70 and 73 percent, respectively, in relapsed CTCL patients having variable levels of CD30 expression treated with ADCETRIS. This compares to objective response rates of 30 to 45 percent from published trials utilizing standard of care treatments in this disease setting. The most common adverse events in these trials were peripheral neuropathy, fatigue, nausea, skin rash, hair loss, diarrhea, muscle pain and neutropenia.

"We are pleased to announce the completion of patient enrollment in the phase 3 ALCANZA clinical trial evaluating ADCETRIS as a potential treatment for CD30-expressing CTCL," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "We look forward to reporting results from the ALCANZA trial in the second half of 2016 to potentially support an ADCETRIS supplemental Biologics License Application seeking a label expansion for use in this setting."

The following highlights data summaries from the JCO publications.

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project (Published on July 20, 2015)

The phase 2 investigator-sponsored trial enrolled CTCL patients with MF or Sézary syndrome, which are types of CTCL. Of the 32 patients enrolled in the study, 30 were evaluable for efficacy and more than half had received three or more prior systemic therapies. The primary endpoint of the trial was objective clinical response rate. The study was led by principle investigator Dr. Youn H. Kim from Stanford University School of Medicine in Stanford, CA. Key findings include:

Twenty-one of 30 patients (70 percent) achieved an objective response across all stages of disease, including Stage IB, Stage IIB and Stage IV/SS. Overall, one patient had a complete response, 20 patients had a partial response, four patients had stable disease and five patients had progressive disease. Two patients were not evaluable for response. Of the patients who had partial responses, seven had near complete responses with over 90 percent skin improvement as measured by modified Severity-Weighted Assessment Tool (mSWAT) scores and eight were still responding to therapy.

Responses appeared to be durable; six- and 12-month Kaplan-Meier estimates indicated continuing responses in 90 percent and 79 percent of patients, respectively.

The most common related adverse events of any grade were peripheral neuropathy (66 percent), fatigue (47 percent), nausea (28 percent), hair loss (22 percent) and neutropenia (19 percent).

The most common Grade 3 or 4 related adverse events were neutropenia (four patients), rash (three patients) and peripheral neuropathy (one patient).

Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Published on August 10, 2015)

Data were published from a phase 2 investigator-sponsored trial evaluating the use of ADCETRIS in CD30-positive CTCL patients, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. The study was conducted by Dr. Madeleine Duvic from the University of Texas MD Anderson Cancer Center in Houston, TX. Among 54 patients enrolled, 48 patients were evaluable at the time of analysis. The primary endpoint of the trial was to evaluate the safety and efficacy of ADCETRIS in CD30-positive CTCL. The key findings include:

Thirty-five of 48 patients (73 percent) achieved an objective response, including 20 of 20 (100 percent) with LyP and/or pcALCL and 15 of 28 (54 percent) with MF. Seventeen patients (35 percent) achieved a complete response.
The most common adverse events were peripheral neuropathy (67 percent), fatigue (35 percent), skin rash (24 percent), diarrhea (15 percent), muscle pain (17 percent), localized skin infection (15 percent), neutropenia (15 percent) and hair loss (11 percent).
The most common Grade 3 or 4 adverse events were neutropenia (three patients), nausea (two patients), unstable angina or myocardial infarction (two patients), infection (two patients), joint pain (two patients), fatigue (one patient), deep vein thrombosis (one patient), pulmonary embolism (one patient), aminotransferase elevation (one patient) and dehydration (one patient).
ALCANZA Trial design

ALCANZA is a randomized, open-label, phase 3 trial of single agent ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with pcALCL or MF. The primary endpoint of the study is overall response rate lasting at least 4 months in patients with CD30-expressing MF or pcALCL. Key secondary endpoints are complete response, progression-free survival and burden of symptoms during treatment.

For more information about the trial, please visit www.clinicaltrials.gov.

About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Cutaneous lymphomas are a category of non-Hodgkin lymphomas that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, CD30 is expressed on skin lesions in at least 50 percent of CTCL patients.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including the phase 3 ALCANZA trial and two additional phase 3 studies, one in frontline classical HL and one in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in more than 55 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS (brentuximab vedotin) is a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS (brentuximab vedotin).

Contraindication

ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.

Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.

Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.

Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.

Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary Toxicity: Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms of pulmonary toxicity, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.

Most Common Adverse Reactions:

ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.

Drug Interactions:

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations:

MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.

On September 9, 2015 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called AccurinsTM, treported that patient dosing is underway in the iNSITE 2 trial, a global, phase 2, two-stage clinical trial of BIND-014 in patients with four tumor histologies (Press release, BIND Therapeutics, SEP 9, 2015, View Source [SID:1234507417]).

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These diseases (cholangiocarcinoma [bile duct cancer], advanced cervical cancer, advanced bladder cancer, and advanced squamous cancer of the head and neck) each affect fewer than 200,000 patients in the U.S., making investigational drugs for these diseases candidates for orphan drug designation by the U.S. Food and Drug Administration. Stage 1 data readout for the iNSITE 2 trial is expected in the first half of 2016.

"The dosing of the first patient in the iNSITE 2 trial further expands the clinical development opportunities of BIND-014," said Hagop Youssoufian, M.Sc., M.D., chief medical officer at BIND Therapeutics. "It also represents a new milestone for the first targeted nanoparticle to enter the clinic by utilizing a rigorous biomarker program that can become a useful aid for more reliable patient selection in the future. The orphan tumor types that we have chosen for iNSITE 2 are all cancers with high unmet need and limited treatment options, representing potential opportunities for rapid development. Our choice was also guided by the activity seen with BIND-014 in our phase 1 trial and the historical role of docetaxel in treating these tumors."

The open-label, phase 2, multi-center two-stage iNSITE 2 clinical trial is designed to determine the activity, safety and tolerability of BIND-014 and will enroll up to 160 patients. In addition, an imaging and biomarker program that can potentially inform the future clinical utility of BIND-014 is also planned. Additional information on this study can be found at: View Source