Researchers at UCLA's Jonsson Comprehensive Cancer Center performed the first complete genomic sequencing of a brain cancer cell line. Sequencing of the extensively studied U87 cell line may lead to better ways of identifying drug targets and in developing in vitro tests to monitor patients to establish treatment results and brain cancer recurrence (news link). The study was published in PLOS Genetics.

The European Commission approved Roche's anticancer drug Herceptin (trastuzumab), in combination with chemotherapy incorporating a fluoropyrimidine and a platinum-based drug, for the treatment of patients with inoperable locally advanced, recurrent, and/or metastatic, HEr2-positive stomach cancer. The approval is based on the results from the international ToGA trial (protocol ID: BO18255; NCT01041404) according to which the overall survival of patients with tumors expressing high levels of HEr2 treated with Herceptin was 16 months compared to 11.8 months among those treated with chemotherapy alone.

St. Jude Children's Research Hospital and Washington University School of Medicine (St. Louis, MO) joined forces to decode the genomes of more than 600 children who have contributed tumor samples for this project. The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project, estimated to cost $65 million over 3 years, is the largest investment to date aimed at understanding the genetic origins of childhood cancer. The project will sequence the entire genomes of both normal and cancer cells from each patient, comparing differences in the DNA to identify genetic errors that lead to cancer (news link).

According to results reported in January 2010, at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer, from the phase II clinical trial with ASA404 (vadimezan) in combination with standard chemotherapy in patients with either squamous or non-squamous non-small cell lung cancer (nsclc), median OS was 14 months in the ASA404 plus chemotherapy arm compared to 8.8 months in the chemotherapy alone arm. One of the advantages of AS404 is that it is effective and well tolerated regardless of nsclc histology. ASA404 is in development by Novartis and Antisoma.

Abbott received European regulatory approval for the Architect human epididymis protein 4 (HE4) test for the diagnosis of ovarian cancer and it is now available in Europe. The Architect HE4 immunoassay is a simple blood test that, combined with other tests such as the CA125 assay, may aid in determining the risk of whether a pelvic mass is benign or malignant. Abbott partnered with Fujirebio Diagnostics in the development of the assay. The test is also available in some countries in Asia Pacific and Latin America, and was recently submitted to the FDA for 510(k) clearance. The Architect HE4 is one of numerous other in vitro tests (IVT) in ovarian cancer being developed by at least 30 companies

The first patient was enrolled in a phase I clinical trial (protocol ID: 2009_698, MK2206-010; NCT01021748) combining two novel targeted anticancer agents, Merck's Akt inhibitor MK-2206 and AstraZeneca's MEK inhibitor AZD6244 (ARRY-886), based on preclinical evidence indicating that this combination would enhance their anticancer properties. This is one of a few trials combining two novel agents at their early stage of development, particularly by two separate companies. Usually, combinations of novel anticancer agents are evaluated in clinical trials when at least one is at a late stage of development or has already received marketing approval.

Enrollment was initiated and the first patient was dosed in a multicenter (n=100), international, pivotal, randomized, controlled, phase III clinical trial, dubbed Braf Inhibitor in Melanoma (BRIM3), with PLX4032 (RG7204), being conducted in the USA, Australia, Canada and Europe, in previously untreated patients with metastatic melanoma. This trial is part of the planned registration program for PLX4032, under development by Plexxikon and Roche. Patients enrolling in this trial are being selected using an investigational companion diagnostic test that detects the BRAF(V600E) mutation, being co-developed in parallel with PLX4032 by Roche Molecular Systems and Plexxikon.

In 2009, the FDA approved 4 NCE/NME anticancer drugs, including ofatumumab (Arzerra, GlaxoSmithKline), pralatrexate injection (Folotyn, Allos Therapeutics), romidepsin (Istodax, Gloucester Pharmaceuticals), and pazopanib (Votrient, GlaxoSmithKline). In addition, new cancer indications were approved for two drugs, bevacizumab (Avastin, Roche) and everolimus (Afinitor, Novartis), both for renal cell carcinoma (RCC). Cervarix, a vaccine against HPV developed by GlaxoSmithKline was also approved for the prevention of cervical cancer.

Adventrx Pharmaceuticals submitted a 505(b)(2) NDA to FDA for ANX-530 (vinorelbine injectable emulsion), a proprietary emulsion formulation of Navelbine seeking approval for the same indications as Navelbine, including non-small cell lung cancer (nsclc). The NDA relies in part on the FDA's findings of safety and effectiveness of a reference drug, based on data from one clinical bioequivalence trial (protocol ID: 530-01; NCT00432562) designed to assess the pharmacokinetic equivalence of ANX 530 and Navelbine.

Pfizer discontinued the phase III clinical trial (protocol ID: A4021016; ADVIGO 1016; NCT00596830) examining the effects of figitumumab (CP-751,871), in combination with carboplatin and paclitaxel as first line treatment in patients with advanced non-adenocarcinoma non-small cell lung cancer (nsclc) because the trial met predefined boundaries for early termination. This follows the suspension of enrollment in this trial in September 2009 when an apparent imbalance of certain serious adverse events was observed, including fatalities, occurring in the figitumumab plus chemotherapy arm.

Alnylam Pharmaceuticals and collaborators from the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT) published new data describing further advancements in the discovery and development of novel lipid-like (lipidoid) formulations for the delivery of RNAi therapeutics (MIT link). A phase I clinical trial with an earlier lipid formulation of an RNAi therapeutic is currently enrolling patients with primary or metastatic liver cancer. Silencing of claudin-3 using lipidoid formulations of small interfering RNA (siRNA) also resulted in the suppression of ovarian tumor growth and metastases (MIT link).

Teva Pharmaceutical Industries and OncoGenex Pharmaceuticals entered into a global license and collaboration agreement to develop and commercialize OGX-011, as well as an agreement to purchase shares in OncoGenex. OGX-011 is expected to be used as adjunct therapy to enhance the effectiveness of chemotherapy and has shown promising results when added to currently available chemotherapies in several tumor types. The companies will collaborate on a global phase III clinical program, with two phase III clinical trials expected to be initiated in 2010, and one by early 2011.

Vion Pharmaceuticals voluntarily filed for Chapter 11 bankruptcy, and is seeking to sell or merge the company and/or its key assets, including two anticancer agents in human clinical development, and two preclinical stage products/technologies.

Ambit Biosciences and Astellas Pharma entered into a worldwide agreement to jointly develop and commercialize FMS-like tyrosine kinase-3 (FLT3) kinase inhibitors in oncology and non-oncology indications, including AC220, a novel, orally available, potent and highly selective small molecule specifically designed as a second generation FLT3 inhibitor, being evaluated in a phase II clinical trial (protocol ID: AC220-002; NCT00989261) in relapsed/refractory acute myeloid leukemia (AML). Under the terms of the agreement, Ambit will receive an upfront cash payment of $40 million and will be eligible for pre-commercialization payments of up to $350 million.

In December 2009, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) gave a positive opinion for the marketing authorization of Amgen's Prolia (denosumab) for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. More on denosumab. . .

An ovewhelming majority (12:1) of ODAC members voted to not recommend the sNDA (99139) of Tarceva for use as a first line maintenance monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (nsclc) that did not progress on first line treatment with platinum-based chemotherapy. Among the committee's concerns were the modest median overall survival (OS) results (12.0 months in the Tarceva arms versus 11.0 months for placebo) of the SATURN trial, and the fact that it was not designed specifically to determine that maintenance therapy with erlotinib after initial chemotherapy was superior than treatment with erlotinib at disease progression.

The FDA allowed resumption of the phase III clinical trial (protocol ID: ECOG-E5103; NCT00433511) of Avastin in combination with standard chemotherapy for the adjuvant treatment of early stage breast cancer; the company is to inform prospective enrollees of the risk of developing heart failure with this regimen.

ChemGenex Pharmaceuticals and Hospira entered into an exclusive agreement to license develop and commercialize ChemGenex's anticancer drug omacetaxine mepesuccinate in Europe, the Middle East and parts of Africa. Applications for marketing approval of omacetaxine have been accepted for regulatory review in both the USA and Europe for treatment of patients with chronic myeloid leukemia (CML) expressing the Bcr-Abl T315I mutation that is refractory to imatinib mesylate, the current standard of care treatment. Under the terms of the agreement, Hospira will make an initial payment of €11.1 million, with the potential for up to an additional €74.1 million in performance milestone payments based on the successful development and commercialization of omacetaxine and, following successful commercialization, ChemGenex will be eligible for royalties on sales in the licensed territory.

Seattle Genetics and Millennium: The Takeda Oncology Company, part of the Takeda Group, entered into an agreement to globally develop and commercialize brentuximab vedotin (SGN-35), an antibody-drug conjugate (ADC) targeting CD30 that is in late stage clinical trials for the treatment of relapsed and refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). In addition, Seattle Genetics entered into a collaboration agreement with GlaxoSmithKline (GSK) under which GSK will pay an upfront fee of $12 million for rights to use Seattle Genetics' ADC technology with multiple antigens to be named by GSK. Seattle Genetics is eligible to receive from GSK up to $390 million in milestones if all ADC in the collaboration are commercialized; mid-single digit royalties on worldwide net sales of any resulting ADC products; material supply and annual maintenance fees; and research support payments for assistance provided to GSK under the collaboration. Also, Genentech terminated, effective June 8, 2010, the collaboration agreement for dacetuzumab (SGN-40), a monoclonal antibody (MAb) targeting CD40 that has been investigated in clinical trials in non-Hodgkin lymphoma (NHL) and multiple myeloma; all rights to dacetuzumab will be returned to Seattle Genetics.

Merck KgaA initiated INSPIRE, a multinational phase III clinical trial with the therapeutic cancer vaccine Stimuvax (BLP25 liposome vaccine) in 450 Asian patients with advanced, inoperable non-small cell lung cancer (nsclc) whose disease either responded or stabilized after primary chemoradiotherapy. The trial is designed to determine if Stimuvax would extend overall survival (OS) in this setting. Accordingly to recentlly reported results of a phase IIb trial of Stimuvax in patients with advanced (Stage IIIb) or metastatic nsclc, among 16 patients 10 were alive without evidence of disease for between 2 and 8.2 years.

Cytokinetics and GlaxoSmithKline (GSK) terminated their collaboration and license agreement regarding GSK-923295, an inhibitor of centromere-associated protein E (CENP-E), with all rights reverting to Cytokinetics effective February 28, 2010. With this termination, Cytokinetics is now seeking to license its portfolio of all 3 of its clinical stage antimitotic drug candidates with a novel mechanism of action.

Positive results were reported from a phase II clinical trial (protocol ID: CP4055-203; NCT00498836) with Clavis Pharma's anticancer drug elacytarabine (Elacyt) in patients with refractory acute myeloid leukemia (AML) in the third line setting. Median survival time (MST) was three times longer (5.3 months versus 1.5 months) compared to historic controls and remission rate was significantly increased (14.8% versus 2.5%, p<0.0001). A phase III registration trial is being planned.

Celgene agreed to acquire Gloucester Pharmaceuticals for $340 million in cash plus $300 million in future USA and international regulatory milestone payments. Gloucester's anticancer drug Istodax (romidepsin) was approved by the FDA in November 2009, for the treatment of CTCL in patients previously treated with at least one systemic therapy.

Roche, Genmab's partner, will discontinue development of RG1507, based on the clinical data to date, the large number of molecules targeting the same pathway presently in clinical development, and the prioritization of the Roche portfolio, and not on any safety concerns.

Incyte entered into a collaboration and license agreement with Novartis for two of its investigational anticancer agents, a Jak2 inhibitor in phase III clinical trials for the treatment of myeloproliferative neoplasms (MPN) and a c-Met inhibitor with an FDA-approved IND application for the treatment of a range of malignancies.

The FDA approved Gloucester Pharmaceuticals' anticancer agent Istodax (romidepsin) for the treatment of cutaneous T-cell lymphoma (CTCL) in patients previously treated with at least one chemotherapeutic regimen. Istodax, a member of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors, is expected to be commercially available in January 2010.

Merck & Co. completed its merger with Schering-Plough; the combined company will operate as Merck & Co and use the trade name Merck in the USA and Canada and MSD elsewhere.

U.S. District Judge Robert Sweet declined to dismiss a lawsuit brought by the American Civil Liberties Union challenging patents held by Myriad Genetics and the University of Utah Research Foundation involving two human genes, BRCA1 and BRCA2 associated with hereditary breast and ovarian cancer, on grounds that genes are 'products of nature' and cannot be patented. The judge allowed the case to proceed as its outcome could have implications for the health of millions of women faced with cancer as well as the future of biomedical research. The lawsuit was brought in Manhattan federal court in May 2009 on behalf of women's health groups, geneticists and scientific associations representing approximately 150,000 researchers, pathologists and laboratory professionals.

GTx received a Complete Response Letter from the FDA requesting an additional trial with toremifene (80 mg) to reduce fractures in men with prostate cancer treated with androgen-deprivation therapy (ADT). The agency identified two deficiencies in the company's submitted phase III clinical trial that must be addressed before the drug can be considered for approval. It has been suggested that one concern is that Toremifene may increase the risk of blood clots, although most of the cases in the phase III clinical trial involved older (>80 years of age) or high risk patients.

Celera entered into an exclusive license agreement for the use of Medical Therapies's midkine patents for the development and commercialization of diagnostic products to address a range of lung cancer-related applications, including risk assessment, early detection, differentiation, prognosis as well as monitoring of reoccurrence and disease progression and response to treatment. Midkine will be incorporated in Celera's R&D efforts to use its in-house identified circulating protein biomarkers for non-small cell lung cancer in a blood-based immunodiagnostic assay to diagnose lung cancer using a simple blood test.

SuperGen and GlaxoSmithKline (GSK) entered into a multi-year collaboration to discover and develop cancer therapeutics based on epigenetic targets. Under the terms of the agreement, SuperGen will progress candidate compounds through to early clinical proof of concept with GSK having the right to exercise an option to further develop and commercialize any resulting products on a global basis. In connection with the transaction, SuperGen will receive $5 million upfront, inclusive of a $3 million common stock investment, priced at a premium to market. Potentially, SuperGen may receive development and commercialization milestones exceeding $375 million, as well as tiered double digit royalties, payable on net sales of any resulting products. SuperGen has 2 agents in clinical and several in preclinical development. In a phase Ib clinical trial, treatment of patients with small cell lung cancer (sclc) or neuroendocrine tumors with MP-470 resulted in an overall clinical benefit rate (CBR) of 54% when it was administered in combination with the standard of care carboplatin containing doublet chemotherapy.

Ligand Pharmaceuticals agreed to acquire Metabasis Therapeutics.

The FDA issued a Complete Response Letter regarding the Biologic License Applications (BLA) for Amgen's Prolia (denosumab) in the treatment and prevention of postmenopausal osteoporosis, requesting additional information that would be needed to complete the review of applications for product approval. For the treatment indications, the FDA is requesting a Risk Evaluation and Mitigation Strategy (REMS) that includes a medication guide, a communication plan, and a timetable for submission of assessments of the REMS. For the prevention indication, the FDA is requesting a new clinical program to support approval. The FDA also requested all updated safety data related to Prolia. Amgen expects to receive a separate response for its application for Prolia in the treatment and prevention of bone loss resulting from hormone ablation in patients with breast and prostate cancer.

In a major development in tissue-based biomarker technology, GE Global Research and Eli Lilly report that for the first time a map has been generated of more than 25 proteins in tumors at the subcellular level. The system combines image analysis of cancer cells and structures with GE's patented visualization tools to provide a color map of protein concentrations within the sample. This approach allows the viewing of a cancer cell's comprehensive biomarker signaling pathway and the interplay of signaling networks inside the tumor. To date, the new technology has been tested successfully on colon and prostate cancer tissue samples and is believed to be applicable to all types of cancer. Mapping a tumor's complex biomarker network is expected to aid drug discovery and improve treatment decisions in the clinic. To date, the goal of personalized medicine has been hampered by the one-at-a-time molecular target identification approach in a disease in which affected cells express multiple putative cancer-causing moieties in several pathways. Additionally, technology at GE that was advanced as a result of this collaboration may lead to the ability to identify stem cells within a tumor that control the malignant phenotype, to potentially discover even more innovative, targeted therapies for the treatment of patients with cancer. GE and Lilly also plan to extend their research agreement to include the study of 4 Lilly oncology molecules that are currently in the company's development pipeline. While the technology is expected to help in the analysis of all malignancies, the two companies will perform specific investigations in breast, ovarian, lung, and possibly gastric cancer.

Dosing was initiated in a registration phase III clinical trial (protocol ID: BO22227, 2008-007326-19; NCT00950300) with a subcutaneous (SC) formulation of Roche's Herceptin (trastuzumab), based on Halozyme Therapeutics' Enhanze technology (rHuPH20, recombinant human hyaluronidase). SC Herceptin would confer a significant advantage to patients with early breast cancer who complete their standard IV-based chemotherapy in combination with Herceptin and go on to be treated with Herceptin monotherapy for the remainder of a year. The Enhanze technology is anticipated to allow patients to self-administer Herceptin with or without the support of a healthcare professional via a simple SC injection. Patients would be treated at their family doctor's office or at home without having to go to a hospital, a significant benefit.

The FDA approved Merck's Gardasil, a recombinant human papillomavirus (HPV) quadrivalent (types 6, 11, 16, and 18) vaccine, for use in boys and men aged 9 to 26 years for the prevention of genital warts caused by HPV types 6 and 11.

The FDA approved GlaxoSmithKline's Cervarix, a recombinant human papillomavirus (HPV) bivalent (types 16 and 18) vaccine, for the prevention of cervical precancer and cervical cancer associated with oncogenic HPV types 16 and 18 for use in girls and young women aged 10 to 25 years. Approval of Cervarix was based on data from clinical trials in more than 30 countries involving a diverse population of nearly 30,000 girls and young women administered the vaccine.

According to the FDA, Pfizer suspended new patient enrollment in a phase III clinical trial (protocol ID: A4021016; NCT00596830), one of the trials in the ADVIGO (ADVancing IGF-IR in Oncology) program, evaluating figitumumab (CP-751,851) in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone, in patients with non-small cell lung cancer (nsclc) because of a higher number of deaths and other adverse events in the figitumumab arm. More than 14 novel agents, including cytotoxics, targeted drugs and immunotherapies, are currently in global phase III clinical trials in nsclc for various indications, including advanced or metastatic, newly diagnosed, recurrent/relapsed, or refractory squamous or non-squamous nsclc.

The FDA's Oncologic Drugs Advisory Committee (ODAC) voted unanimously (10-0) in support of approval of GlaxoSmithKline's oral anticancer drug Votrient (pazopanib) for the treatment of patients with advanced renal cell carcinoma (RCC). Specifically, the panel found the benefit-to-risk profile acceptable in patients with advanced RCC. The decision was based on data from a phase III pivotal trial (protocol ID: VEG105192; NCT00334282) presented at the 2009 meeting of the American Society of Clinical Oncology (ASCO). In this trial, treatment with pazopanib (800 mg), administered orally once daily, resulted in a progression-free survival (PFS) of 9.2 months compared to 4.2 months with placebo. However, the risk of hepatotoxicity caused concern and other serious adverse events were common.

Allos Therapeutics launched Folotyn (pralatrexate injection) in the USA through its commercial organization after the FDA granted accelerated approval to the drug for use as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

Treatment with panitumumab (Vectibix; Amgen), in combination with standard chemotherapy, improved progression-free survival (PFS) in 2 large, international, phase III clinical trials in patients with metastatic colorectal cancer expressing wild type (wt) Kras. In the trial (protocol ID: 20050203; NCT00364013) in the first line setting, PFS was 9.6 months with panitumumab, in combination with FOLFOX, compared to FOLFOX alone, a 1.6-month advantage for a hazard ratio of HR=0.80 (p=0.02). In the trial (protocol ID: 20050181; NCT00339183) in the second line setting, PFS was 5.9 months with panitumumab in combination with FOLFIRI compared to 3.9 months with FOLFIRI alone, a 2-month advantage for a hazard ratio of HR=0.73 (p=0.004).

Pfizer has initiated a phase III clinical trial with PF-2341066 in patients with advanced non-small cell lung cancer harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK translocation.

The independent Data Monitoring Committee (DMC) of the randomized, placebo-controlled, phase III SUCCEED (Sarcoma mUltiCenter Clinical Evaluation of the Efficacy of riDaforolimus) clinical trial (protocol ID: AP23573-07-302; NCT00538239) completed the first interim efficacy analysis as specified by the trial's protocol and recommended that the trial of Ariad Pharmaceuticals' oral drug ridaforolimus in patients with metastatic sarcoma continue to full patient enrollment and completion.

ChemGenex Pharmaceuticals completed its New Drug Application (NDA) submission to the FDA for Omapro (omacetaxine mepesuccinate) being developed for the treatment of patients with chronic myeloid leukemia (CML) refractory to imatinib and harboring the Bcr-Abl T315I mutation.

Based on the recommendations by an Independent Data Monitoring Committee (IDMC), sanofi-aventis and Regeneron Pharmaceuticals discontinued the phase III clinical trial (protocol ID: EFC10547; AVE0005; EudraCT 2007-003476-19; NCT00574275), dubbed VANILLA, that evaluated aflibercept (VEGF Trap) plus gemcitabine versus placebo plus gemcitabine as first line treatment of metastatic pancreatic cancer. As part of a planned interim efficacy analysis, the IDMC determined that, in this trial, the addition of aflibercept to gemcitabine would not result in a statistically significant improvement in the primary endpoint of overall survival (OS) compared to placebo plus gemcitabine.

The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 12-1 and 11-1, respectively, regarding the efficacy and safety of GlaxoSmithKline's vaccine Cervarix, noting that according to clinical data, Cervarix was highly effective and well tolerated in girls and young women for the prevention of cervical precancer and cervical cancer related to human papillomavirus (HPV) types 16 and 18.

Additional news items are summarized in the News Module.