1stOncology™: Cancer Intelligence Service – Page 17105 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Merck Announces Phase 3 Study of Single-Dose EMEND® (fosaprepitant dimeglumine) for Injection Regimen Met Primary Endpoint in Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

On June 29, 2015 Merck reported results from a Phase 3 study investigating the safety and efficacy of single-dose EMEND (fosaprepitant dimeglumine) for Injection, Merck’s substance P/neurokinin (NK-1) receptor antagonist, in combination with other anti-vomiting medicines, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adult cancer patients receiving moderately emetogenic (vomit-inducing) chemotherapy (MEC) (Press release, Merck & Co, JUN 29, 2015, View Source [SID:1234506001]). In the study, the first to evaluate an intravenous NK-1 receptor antagonist for the prevention of CINV associated with MEC, the single-dose EMEND for Injection regimen provided greater protection from nausea and vomiting following administration of chemotherapy versus an active control of placebo with other anti-vomiting medicines. These data were presented in an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting on Supportive Care in Cancer (Abstract #27-02-O) in Copenhagen (June 25-27, 2015).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"The results from this important Phase 3 trial are very encouraging as they are the first study to evaluate EMEND for Injection in a combination regimen for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy – and show the potential to use a single day antiemetic regimen," said Dr. Bernardo L. Rapoport, principal investigator for the study and chief medical oncologist, Medical Oncology Centre of Rosebank, Johannesburg, South Africa.

"Nausea and vomiting remain a significant burden for patients receiving chemotherapy and we look forward to submitting these data for EMEND for Injection to the U.S. Food and Drug Administration," said Stuart Green, vice president, clinical research, Merck Research Laboratories. "This study builds on our decade of research for EMEND and Merck’s overall commitment to help people with cancer."

EMEND for Injection, a substance P/Neurokinin-1 (NK1) receptor antagonist approved for use in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer (HEC) chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of MEC. EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended.

In the U.S., the single-dose regimen of EMEND for Injection is approved for use associated with HEC. Merck plans to submit these recent data to the Food and Drug Administration in the second half of 2015 to seek approval for a regimen containing single-dose EMEND for Injection for the prevention of CINV associated with MEC.

About Phase 3 Study for Single-Dose EMEND for Injection in MEC

In this global randomized, Phase 3, double-blind study, more than 1,000 patients receiving MEC were randomly assigned to receive either single-dose EMEND for Injection (150 mg) in combination with ondansetron capsules (16 mg) and dexamethasone capsules (12 mg) (n=504) on day one (followed by oral placebo for ondansetron on days two and three) or an active control regimen consisting of placebo (saline IV) in combination with ondansetron (16 mg) and dexamethasone (20 mg) (n=497) on day one (followed by 8 mg ondansetron on days two and three). The primary endpoint of the study was complete response (CR) (as measured by no vomiting and no use of rescue medication for nausea or vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were CR after the first dose of chemotherapy in the acute phase (0 to 24 hours) and in the overall phase (0-120 hours), as well as no vomiting in the overall phase.

Single-Dose EMEND for Injection Regimen Achieved Superior Control of CINV

For the primary study endpoint, EMEND for Injection regimen provided higher incidence of CR in days 2 through 5 – with CR observed in 78.9 percent of patients receiving the EMEND for Injection regimen versus 68.5 percent in the active control group (p <0.001). For the secondary endpoints, in the acute phase, CR was observed in 93.2 percent of patients receiving the EMEND for Injection regimen versus 91 percent in the active control group (p = 0.184). In the overall phase, the incidence of CR was observed in 77.1 percent of patients receiving the EMEND for Injection regimen versus 66.9 percent in the active control group (p <0.001). Additionally, a significantly greater proportion of patients receiving the EMEND for Injection regimen experienced no vomiting in the overall phase (82.7 percent with EMEND vs 72.9 percent in the active control group) and delayed phase (83.9 percent with EMEND vs 75.1 percent in the active control group) (both p <0.001) – with a favorable trend in the acute phase (94.8 percent with EMEND vs 92 percent in the active control group).

The most common adverse events (across all grades) in the EMEND for Injection regimen and active control group included fatigue (15.1 percent and 12.9 percent), diarrhea (12.7 percent and 11.3 percent), and constipation (9.3 percent and 10.5 percent). Treatment-related adverse events were observed in 8.5 percent of patients receiving the EMEND for Injection regimen and in 9.1 percent of patients in the active control group. Serious treatment-related adverse events were observed in 0.2 percent of patients receiving the EMEND for Injection regimen and in 0.4 percent of patients in the active control group.

Selected Important Safety Information for EMEND (fosaprepitant dimeglumine) For Injection

EMEND for Injection is contraindicated in patients who are hypersensitive to EMEND for Injection, aprepitant, polysorbate 80, or any other components of the product. Known hypersensitivity reactions include flushing, erythema, dyspnea, and anaphylactic reactions.

Aprepitant, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

EMEND for Injection should be used with caution in patients receiving concomitant medications, including chemotherapy agents that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND for Injection could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND for Injection is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND for Injection is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.

Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, EMEND did not influence the pharmacokinetics of docetaxel or vinorelbine.

Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

There have been isolated reports of immediate hypersensitivity reactions, including flushing, erythema, dyspnea, and anaphylaxis, during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who have experienced these symptoms during first-time use.

Coadministration of EMEND for Injection with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of EMEND for Injection with each chemotherapy cycle.

The efficacy of hormonal contraceptives (including birth control pills, skin patches, implants, and certain IUDs) may be reduced during coadministration with and for 28 days after the last dose of EMEND for Injection. Alternative or backup methods of contraception should be used during treatment with and for 1 month after the last dose of EMEND for Injection.

Chronic continuous use of EMEND for Injection for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

In clinical trials of EMEND in patients receiving HEC, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence of 1% or greater, were hiccups (4.6% EMEND vs 2.9% standard therapy), asthenia/fatigue (2.9% vs 1.6%), increased ALT (2.8% vs 1.5%), increased AST (1.1% vs 0.9%), constipation (2.2% vs 2.0%), dyspepsia (1.5% vs 0.7%), diarrhea (1.1% vs 0.9%), headache (2.2% vs 1.8%), and anorexia (2.0% vs 0.5%).

In a clinical trial evaluating safety of the 1-day regimen of EMEND for Injection compared with the 3-day regimen of EMEND, the safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients who received fosaprepitant (3.0%) than in those who received aprepitant (0.5%). Those infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.

About Chemotherapy Induced Nausea and Vomiting (CINV)

Chemotherapy Induced Nausea and Vomiting (CINV) is a common side effect of chemotherapy caused by injured stomach cells that start the process of nausea and vomiting and can directly activate the area of the brain responsible for producing nausea and vomiting. The two main types of CINV are acute and delayed. Acute happens within the first 24 hours of receiving chemotherapy. Delayed happens from day 2 to day 5 after chemotherapy. The amount and timing of CINV can vary. Some chemotherapies cause acute nausea and vomiting. Others cause acute nausea and vomiting followed by another period of delayed nausea and vomiting.

Celgene and Juno Announce Ten-Year Collaboration to Advance Potentially Groundbreaking Immunotherapies for Patients with Cancer and Autoimmune Diseases

On June 29, 2015 Celgene and Juno reported a global collaboration for the development and commercialization of immunotherapies (Press release, Celgene, JUN 29, 2015, View Source [SID:1234506009]). The two companies will leverage T cell therapeutic strategies to develop treatments for patients with cancer and autoimmune diseases with an initial focus on Chimeric Antigen Receptor Technology (CAR-T) and T Cell Receptor (TCR) technologies.

"This transaction strengthens Celgene’s position in the emerging and transformative area of immuno-oncology," said Bob Hugin, Chairman and CEO of Celgene. "Juno has assembled world class experts and built impressive capabilities and technologies in the areas of T cell biology and cellular therapy; we believe this long-term collaboration enhances the potential of both companies to deliver transformational therapies to patients with significant unmet medical needs."

Know more, wherever you are:
Latest on CAR/TCR Therapies in Oncology, book your free 1stOncology demo here.

"Celgene is the ideal partner for Juno to help us realize the full potential of our science and clinical research while maintaining the independence we, our employees, partners, and investors believe is so critical for true innovation," said Hans Bishop, CEO of Juno. "This unique collaboration is designed to catalyze and create tremendous ongoing scientific and product development synergy by leveraging each company’s strengths and assets. In addition to its established global presence and commercial reach, Celgene has leading small molecule and protein capabilities that complement Juno’s advanced engineered T cell capabilities. By doing this together, we believe we can more quickly and effectively develop potentially disruptive therapies in this new field of medicine and make them more readily available to patients worldwide."

Under the terms of the collaboration, Celgene has the option to be the commercialization partner for Juno’s oncology and cell therapy auto-immune product candidates, including Juno’s CD19 and CD22 directed CAR-T product candidates. B-Cell Maturation Antigen (BCMA) is excluded as a target in this collaboration.

For Juno-originated programs co-developed under the collaboration:

Juno will be responsible for research and development in North America and will retain commercialization rights in those territories;
Celgene will be responsible for development and commercialization in the rest of the world, and will pay Juno a royalty on sales in those territories; and
Celgene has certain co-promotion options:
Celgene will initially be eligible to select two programs, excluding CD19 and CD22, to be subject to a global profit sharing agreement under which the companies will share worldwide expenses and profits equally, except in China; and
Additionally, subject to additional obligations, Celgene may select a third program.
Juno will have the option to enter into a co-development and co-commercialization agreement on certain Celgene-originated development candidates that target T Cells. For any such Celgene-originated programs co-developed under the collaboration:

The parties will share global costs and profits with 70% allocated to Celgene and 30% allocated to Juno; and
Celgene will lead global development and commercialization, subject to a Juno co-promote option in the US and certain EU territories.
Upon closing, Juno will receive an upfront payment of approximately $150 million, and in addition Celgene will purchase 9,137,672 shares of Juno’s common stock at $93.00 per share. In conjunction with this stock purchase:

Celgene will receive the right to nominate a member to Juno’s board of directors;
During the 10-year term of the collaboration, Celgene will have the right to purchase additional equity in Juno during specified windows and at specified market premiums subject to satisfaction of certain conditions by each party including Juno opting in on select Celgene programs, such that, at a maximum, Celgene could own up to 30% of Juno’s common stock then outstanding; and
Celgene has entered into a standstill agreement and agreed to certain lock-up provisions on its share ownership.
This transaction has been approved by the boards of directors of both companies. Celgene and Juno currently expect to complete the transaction during the third quarter of 2015, subject to the expiration or termination of applicable waiting periods under all applicable antitrust laws and satisfaction of other usual and customary closing conditions.

RedHill Biopharma Initiates Phase I/II Study of ABC294640 for Refractory Lymphoma

On June 29, 2015 RedHill Biopharma reported that it has initiated a Phase I/II clinical study in the U.S. evaluating ABC294640 in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) (Press release, RedHill Biopharma, JUN 29, 2015, View Source [SID:1234506006]).

ABC294640 is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, with anti-inflammatory and anti-cancer activities, targeting multiple inflammatory, gastrointestinal (GI) and oncology indications. SK2 is an innovative molecular target for anti-cancer therapy because of its critical role in catalyzing the formation of the lipid-signaling molecule sphingosine 1-phosphate (S1P), which is known to regulate cell proliferation and activation of inflammatory pathways. By inhibiting SK2, ABC294640 could potentially be effective in treating multiple inflammatory, oncologic and gastrointestinal diseases.

Know more, wherever you are:
Latest on Drug Target in Oncology, book your free 1stOncology demo here.

The Phase I/II study is intended to evaluate the safety and tolerability of ABC294640, as well as provide a preliminary evaluation of efficacy of the drug in patients with refractory/relapsed DLBCL, primarily patients with HIV-related DLBCL. Up to 33 patients are expected to be enrolled in the study, which will be conducted at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans. The study is funded primarily by a grant awarded by the National Cancer Institute (NCI) Small Business Technology Transfer (STTR) program. Dr. Chris Parsons, MD, an associate professor in the Departments of Medicine and Microbiology, Immunology & Parasitology at LSUHSC, is the lead investigator for the study.

Dr. Terry Plasse, MD, RedHill’s Medical Director, said: "We are excited to initiate this translational study with ABC294640, carrying Dr. Parson’s laboratory evaluations into an important clinical population of patients with refractory/relapsed diffuse large B-cell lymphoma, primarily patients with HIV-related DLBCL, a group of patients with substantial unmet medical needs. RedHill continues to advance towards additional Phase II clinical studies with ABC294640 as a radioprotectant in cancer patients undergoing therapeutic radiotherapy and, subject to a pending NCI/SBIR grant, multiple myeloma."

DLBCL is the most common subtype of non-Hodgkin’s lymphoma, accounting for an estimated 30% of the 70,000 projected non-Hodgkin’s lymphoma cases diagnosed in the U.S. in 20151. Many DLBCLs are etiologically linked to the human viruses which encode unique oncogenes contributing to tumor onset and progression. Standard treatments for DLBCL exhibit limited efficacy and incur significant toxicities.

The Phase I/II study was initiated following positive pre-clinical studies, led by Dr. Parsons, indicating the therapeutic activity of ABC294640 for virus-associated DLBCL, in an established xenograft model for Kaposi’s sarcoma-associated herpesvirus-associated DLBCL, including reversal of disease progression for established tumors. The pre-clinical studies were performed in parallel with a successful Phase I study that demonstrated the drug’s safety and assessed its pharmacokinetics and pharmacodynamics in cancer patients with advanced solid tumors.

RedHill acquired the rights to ABC294640 in March 2015 from U.S.-based Apogee Biotechnology Corporation ("Apogee"). Prior to the acquisition, Apogee completed numerous successful pre-clinical studies with ABC294640 in GI, inflammation, radioprotection and oncology models, as well as a successful Phase I clinical study in cancer patients with advanced solid tumors. The open-label, dose-escalation, Phase I clinical study demonstrated the drug’s safety and assessed its pharmacokinetics and pharmacodynamics in cancer patients with advanced solid tumors. The development of ABC294640 was funded to date primarily through grants and contracts in excess of $14 million from U.S. federal and state government agencies, such as the FDA, Department of Defense (DoD) and the National Institutes of Health (NIH), including the National Cancer Institute and BARDA.

A second Phase II study of ABC294640 is planned to evaluate ABC294640 as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy. RedHill also plans a third Phase II clinical study for the treatment of multiple myeloma, subject to funding by a pending grant from the National Cancer Institute.

The Phase I/II study with ABC294640 for refractory/relapsed diffuse large B-cell lymphoma is registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health which provides public access to information on publicly and privately supported clinical studies: View Source

About ABC294640:

ABC294640 is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor, administered orally, with anti-cancer and anti-inflammatory activities, targeting multiple potential inflammatory, oncology and gastrointestinal indications. By inhibiting the SK2 enzyme, ABC294640 blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid that promotes cancer growth and pathological inflammation. ABC294640 was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in inflammatory, GI, radioprotection and oncology models, as well as a Phase I clinical study in cancer patients with advanced solid tumors. A Phase I/II clinical study evaluating ABC294640 in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) has been initiated in the U.S. The development of ABC294640 was funded to date primarily through grants and contracts in excess of $14 million from U.S. federal and state government agencies.

Juno Announces FDA Acceptance of Investigational New Drug Application for JCAR017 in Relapsed/Refractory B Cell Non-Hodgkin Lymphoma

On June 29, 2015 Juno reported the U.S. Food and Drug Administration (FDA) accepted the Company’s investigational new drug (IND) application for JCAR017 for patients with relapsed/refractory (r/r) B cell non-Hodgkin lymphoma, or NHL (Press release, Juno, JUN 29, 2015, View Source [SID:1234506005]). JCAR017 is a chimeric antigen receptor (CAR) T cell product candidate targeting CD19, a protein expressed on the surface of most B cell leukemias and lymphomas.

The IND enables Juno to initiate a multi-center Phase I trial exploring JCAR017 for r/r NHL, scheduled to begin in 2015, with the potential to advance to a registration trial in 2016.

"Based on the encouraging results of JCAR017 in pediatric acute lymphoblastic leukemia, we are excited to begin investigating this product candidate in non-Hodgkin lymphoma," said Mark Frohlich, M.D., Juno EVP of development and portfolio strategy. "FDA acceptance of the JCAR017 IND for this multi-institutional study is an important milestone for Juno. Together with our planned fully-human CD19 CAR-T cell trial, combination study with AstraZeneca’s anti-PDL-1 antibody, and ongoing translational clinical trial with JCAR014, it will provide important biologic insights that will inform our future strategies."

In collaboration with Seattle Children’s Research Institute, Juno continues to investigate JCAR017 in pediatric patients with r/r acute lymphoblastic leukemia (ALL). Results of a Phase I study to date demonstrated 91 percent of patients achieved a complete remission, all of which were documented by flow cytometry. Adverse events were consistent with what has been previously reported. The results were presented in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2015 in Philadelphia.

About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.

CytRx Announces Presentation of Interim Phase 2 Data for Aldoxorubicin for HIV-Related Kaposi’s Sarcoma

On June 29, 2015 CytRx reported the presentation of interim results from its ongoing open-label Phase 2 pilot study evaluating the efficacy and safety of aldoxorubicin for the treatment of Kaposi’s Sarcoma (KS) in HIV-infected patients (Press release, CytRx, JUN 29, 2015, View Source [SID:1234506004]). The data will be presented on Wednesday, July 1, 2015 during a poster session at the 18th International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents in Hollywood, Florida.

For the study, patients with biopsy-confirmed KS were administered 100 or 150 mg/m2 aldoxorubicin (75 or 112 mg/m2 doxorubicin equivalents) IV every three weeks. At the time of presentation, preliminary analyses were available for nine patients who received at least six cycles of drug (mean = 6.3 cycles). Four patients had received prior Doxil chemotherapy. Of these 9 patients, 6 (67%) demonstrated a partial response (PR) to aldoxorubicin at the end of study visit (EOS), and 7 (78%) demonstrated PR within 4 months of EOS. Doxorubicin could be detected in all tumor biopsies and higher doxorubicin concentrations were demonstrated within KS lesions relative to skin next to the lesions for 3/4 (75%) patients for whom adequate tissue was available for analysis. Five of 6 (83%) patients receiving aldoxorubicin and for whom data are available exhibited reduced intratumoral viral loads during therapy. A subset of patients also exhibited improvements in quality of life during treatment, and all patients exhibited either improvement or stability in immunologic and virologic HIV treatment parameters. Aldoxorubicin was well-tolerated, with only 2 patients (22%) experiencing a grade 4 adverse event (transient neutropenia and anemia), and overall AEs (44%) were mild and compared favorably with AE rates from other trials enrolling KS patients representing urban, minority-predominant populations.

"KS remains an important cause of morbidity and mortality for HIV-infected patients worldwide, yet significant toxicities limit drug exposure and outcomes for many patients when antiretroviral therapy is combined with standard treatments like liposomal doxorubicin (Doxil)," said Chris Parsons, MD, Associate Professor in the Departments of Medicine and Microbiology, Immunology, & Parasitology at the Louisiana State University Health Sciences Center, and principal investigator of the study. "These data demonstrate aldoxorubicin’s ability to leverage cancer biology to preferentially release chemotherapeutic drugs in tumors, thereby limiting toxicity, increasing drug exposure and improving outcomes. We remain highly encouraged by the activity and tolerability of aldoxorubicin in this study, and look forward to its continued enrollment and final results."

This open-label Phase 2 clinical trial is expected to enroll up to 30 patients, randomly assigned to two equally sized treatment arms which will receive aldoxorubicin at 100 or 150 mg/m2 by 30-minute intravenous infusion. Because the KS patients in the study have compromised immune systems, the aldoxorubicin dosages administered in the trial are lower than those administered in the Company’s clinical testing of aldoxorubicin in patients with soft tissue sarcomas. Patients with advanced KS receive aldoxorubicin on day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. The primary objectives of preliminary efficacy include evaluation of the size, number and nodularity of skin lesions, change in size and number of lung lesions and changes in the number of tumor cells that express viral DNA (Kaposi sarcoma-associated herpesvirus, the etiologic agent of KS). The Company is also evaluating the level of aldoxorubicin uptake into lesions. Safety is being assessed through monitoring of adverse events and the ability to remain on assigned treatment. The trial is being conducted at the Louisiana State University Health Sciences Center in New Orleans, LA.

KS is an orphan indication in the U.S.

About Kaposi’s Sarcoma

Kaposi sarcoma is a cancer that causes lesions (abnormal tissue) to grow in the skin; the mucous membranes lining the mouth, nose, and throat; lymph nodes; or other organs. The lesions are usually purple and are made of cancer cells, new blood vessels, red blood cells, and white blood cells. Kaposi sarcoma is different from other cancers in that lesions may begin in more than one place in the body at the same time. KS remains the most common HIV-associated tumor worldwide. The condition is also endemic in certain parts of Central Africa and Central and Eastern Europe.

About Aldoxorubicin

The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.