Biologics' Power Play in the Global Oncology Market

By Patricia Van Arnum - DCAT Editorial Director

June 3, 2015

The annual meeting of the American Society of Clinical Oncology (ASCO) is an important event for pharmaceutical companies to share results of their most promising oncology drugs. With this year's meeting just completed, what were the highlights and key pipeline contenders in the $100 billion global oncology market? DCAT Value Chain Insights (VCI) examines the highlights.

Although small-molecules dominate the industry's oncology pipeline, biologics dominate one of the promising areas of new oncology drug development, immuno-oncology. DCAT Value Chain Insights looks at the most promising biologics in the pharmaceutical majors' commercial portfolios and pipeline for oncology drugs and the network of alliances to advance these candidates.

Growth drivers in the global oncology market
Earlier diagnosis, longer treatment duration, and increased effectiveness of drug therapies are contributing to rising levels of spending on medicines for cancer care. Although total global spending on oncology medicines, including therapeutic treatments and supportive care, reached the $100 billion threshold in 2014, the share of total medicine spending of oncologics increased only modestly, according to a recent IMS analysis. Growth in global spending on cancer drugs, measured using ex-manufacturer prices and not reflecting off-invoice discounts, rebates, or patient access programs, increased at a compound annual growth rate (CAGR) of 6.5% on a constant-dollar basis during the past five years. Oncology spending remains concentrated among the US and five largest European Union (EU) countries (France, Italy, Germany, Spain, and the UK), which together account for 66% of the total market. Growth in the US has risen more slowly, at 5.3% CAGR, with the market reaching $42.4 billion in 2014. Overall, oncology drug spending has risen slightly as a percentage of total drug spending over the past five years in all regions, most notably in the EU5 countries (France, Germany, Italy, Spain, and the UK), where oncology now represents 14.7% of total drug spending, up from 13.3% in 2010. Within the US, the increase has been more modest, rising to 11.3% from 10.7% over the same period. In the nine major developed markets, growth spending on oncology drugs has increased sharply, rising from $1.4 billion spending growth in 2013 to $7.4 billion spending growth in 2014, according to the IMS analysis.

Most of the higher spending growth is due to increased volume demand for branded products in addition to newly launched products. The impact on patent expiries on reducing oncology spending has declined from about $2.9 billion in 2011 to $1.3 billion in 2014 as fewer molecules lost and faced competition from generics. The rising prevalence of cancer and greater patient access to treatments in pharmerging nations continues to grow and now accounts for 13% of the market. Pharmerging markets, as defined by IMS, refer to the most promising emerging markets for pharmaceuticals and include: Tier 1 pharmerging countries (China), Tier II pharmerging countries (Brazil, Russia, and India), and Tier 3 pharmerging markets (Mexico, Turkey, Venezuela, Poland, Argentina, Saudi Arabia, Indonesia, Colombia, Thailand, Ukraine, South Africa, Egypt, Romania, Algeria, Vietnam, Pakistan and Nigeria). Overall on a global basis, spending on oncology drugs, including therapies for supportive care, is expected to increase at a CAGR of 6% to 8% through 2018 to bring the global oncology market to $117 billion to $142 billion in 2018.

Targeted therapies have dramatically increased their share of the total global oncology spend. Targeted therapies now account for nearly 50% of total spending and have been growing at 14.6% CAGR since 2009. Targeted therapies now represent 48% of total oncology medicines spending, up from 36% in 2010. Meanwhile in the five-year period of 2010 to 2014, cytotoxic, hormonal, and supportive therapies have remained at about $52 billion in annual sales, according to the IMS report.

Biologics dominate immunoncology
On a pipeline basis, key advances include new "immuno-oncologics" that hold out the promise of improved survival with lower toxicity for some patients, as well as combination therapies that can address multiple pathways in a tumor, potentially leading to substantial increases in survival. Among the immuntherapies, key recent approvals or pipeline candidates include: Bristol-Myers Squibb's ipilimumab, a monoclonal antibody (mAb) directed against cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), approved in 2011; PD-1 targeted therapies approved in 2014 (Bristol-Myers Squibb's Opdivo (nivolumab) and Merck & Co.'s Keytruda (pembrolizumab); and chimeric antigen receptor-T cells (CARTs), cell-based therapies that condition a patient's T cells to recognize a specific cancer.

In terms of combination oncology drugs, the IMS study points out that a large number of combinations will launch over the next six years with an inflection point in the 2020-2021 time frame, when 15 oncology combination are expected to launch in 2020 and 34 in 2021 and beyond. Roche is developing the largest number of combinations, and most manufacturers have multiple combinations in their pipelines. Most combinations include agents from two or more manufacturers although Roche, Bristol-Myers Squibb, AstraZeneca, and Janssen are studying combinations of a new molecular entity and an existing agent that are both made by a single manufacturer. Additionally, therapeutic effectiveness in multiple genetic subpopulations is being improved through the use of real-world evidence from deep biomarker data linked to treatment information. Molecular diagnostics are transforming drug development and patient selection, but only one-third of new oncology drugs have an identified biomarker at the time of launch, according to the IMS study.

Overall, oncology pipelines have produced 45 new drugs for more than 53 uses from 2010 to 2014, according to the IMS study. In 2014, there were 10 new oncology drugs launched globally, including five biologics: two new immunotherapies; two checkpoint inhibitors (Bristol-Myers Squibb's nivolumab and Merck & Co.'s pembrolizumab); a bi-specific T-cell engager (a new class of drug) as represented by Amgen's blinotumomab; Eli Lilly's ramucirumab; and Janssen's siltuximab.

Key company highlights
AstraZeneca. AstraZeneca and MedImmune, the company's global biologics research and development arm, presented encouraging results from their combination-focused immuno-oncology portfolio at the recent ASCO annual meeting. AstraZeneca's key drug candidate is MEDI4736, an anti-programmed cell death ligand 1 (PD-L1) mAb being studied as a monotherapy and in combination with other immuno-oncology and small-molecule therapies across different tumor types and tumor biology. MEDI4736 is being studied with another mAb, tremelimumab, in both PD-L1 positive and PD-L1 negative advanced non-small cell lung cancer (NSCLC) patients (Phase I). Other data at ASCO underpinned the potential for MEDI4736 in combination with other immuno-oncology and small molecules in melanoma and lung cancer. The company presented data on the use of MEDI4736 in combination with the following: Novartis' BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in patients with advanced melanoma; Iressa (gefitinib), AstraZeneca's epidermal growth factor receptor (EGFR) mutation-positive tyrosine kinase inhibitor (TKI) in advanced NSCLC; and AZD9291, AZD6094, or selumetinib in EGFR-mutant lung cancer patients who have progressed following therapy with an EGFR-TKI. AstraZeneca is also developing aPD-L1 companion diagnostic test with Ventana Medical Systems and MedImmune as a biomarker to predict response to MEDI4736. By 2020, the company is aiming to bring six new cancer medicines to market.

Also in 2015, AstraZeneca and Eli Lilly and Company have formed a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with Eli Lilly's Cyramza (ramucirumab), a vascular endothelial growth factor (VEGF) VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumors.

Earlier this year, AstraZeneca formed an exclusive $450 million collaboration agreement with Celgene Corporation, for the development and commercialization of AstraZeneca's investigational immunotherapy, MEDI4736. , MEDI4736 will be assessed both as monotherapy and in combination with other AstraZeneca and Celgene potential and existing cancer medicines. Over time, the collaboration could expand to include other assetsUnder the terms of the agreement, Celgene will make an upfront payment of $450 million to AstraZeneca in relation to MEDI4736. Celgene will lead on development across all clinical trials within the collaboration and will take on all research and development costs until the end of 2016, after which they will take on 75% of these costs. Celgene will also be responsible for global commercialization of approved treatments. AstraZeneca will continue to manufacture and book all sales of MEDI4736 and will pay a royalty to Celgene on worldwide sales in hematological indications. The royalty rate will start at 70% and will decrease to approximately half of the sales of MEDI4736 in haematological indications over a period of four years. The collaboration, which is subject to closing and antitrust review, is expected to become effective in the second quarter of 2015.

Also, AstraZeneca partnered in November 2014 with Pharmacyclics, Inc. (which recently acquired by AbbVie) and Janssen Research & Development, LLC , have entered into a clinical trial collaboration to evaluate the efficacy and safety of AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with Imbruvica (ibrutinib), an oral Bruton's tyrosine kinase inhibitor, co-developed by Pharmacyclics and Janssen and commercialized outside the US by Janssen affiliates. The study will assess the combination as a treatment for patients with hematological cancers, including diffuse large B-cell lymphoma and follicular lymphoma, which are investigational uses for both compounds.

Commenting on the company's immuno-oncology combination data presented at ASCO, AstraZeneca Chief Executive Officer, Pascal Soriot, said in a company release: "Immuno-oncology has continued to take center stage at ASCO this year, as we see more evidence of the significance of this approach for patients. At AstraZeneca, we have been clear in our belief that combinations hold the key to transforming clinical practice for the patients not benefiting from the currently available immunotherapies. The data presented on the combination of MEDI4736 and tremelimumab are truly exciting. As the frontrunner combination of two immuno-oncology molecules in non-small cell lung cancer, it is demonstrating promising clinical activity, in particular in the majority of patients who have low or no PD-L1 expression. With our longstanding expertise in developing highly effective small molecule medicines, including Lynparza and AZD9291, we are now also seeing the potential of combining these targeted medicines with immuno-oncology molecules to deliver efficacious and durable treatment to patients."

Bristol-Myers Squibb. Bristol-Myers Squibb's Opdivo, which was approved in 2014 to treat melanoma, is being studied for other tumor types. At the ASCO meeting, the company reported positive Phase III data for advanced squamous non-small cell lung cancer. The company also reported positive Phase III results for Opdivo in combination with the company's other immunocology drug, Yervoy for treating advanced melanoma, and positive Phase I/II data for Opdivo in hepatocellular carcinoma, a form of liver cancer. Earlier this month, Bristol-Myers Squibb reported that the US Food and Drug Administration accepted for filing and review Bristol-Myers Squibb's supplemental biologics license application (sBLA) for Opdivo (nivolumab) + Yervoy (ipilimumab) regimen in patients with previously untreated advanced melanoma. The FDA also granted priority review for this application. The projected FDA action date is September 30, 2015.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that has received approval from the FDA as a monotherapy in two cancer indications. In the US, Opdivo is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 5, 2015, Opdivo received FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials, as monotherapy or in combination with other therapies in which more than 7,000 patients have been enrolled worldwide.

Merck & Co. In line with the ASCO annual meeting, Merck & Co. Inc. announced that the US FDA has accepted for review its sBLA for the company's anti-PD-1 therapy, Keytruda (pembrolizumab), a humanized mAb that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose disease has progressed on or after platinum-containing chemotherapy and an FDA-approved therapy for EGFR or ALK genomic tumor aberrations, if present. The FDA granted priority review with a PDUFA, or target action, date of October 2, 2015; the sBLA will be reviewed under the FDA's Accelerated Approval program. As previously announced, a premarket approval application (PMA) was submitted by Dako North America, Inc., an Agilent Technologies Company, for an immunohistochemistry companion diagnostic test that detects PD-L1 expression, PD-L1 IHC 22C3 PharmDx.

Keytruda is now approved in the United States for treating unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor. Merck is advancing a broad clinical development program for Keytruda with more than 100 clinical trials across more than 30 tumor types and enrolling more than 16,000 patients, both as a monotherapy and in combination with other therapies. In line with the annual meeting of ASCO, Merck also announced additional partnerships for its immuno-therapy pipeline. The pacts involve the clinical development of Keytruda in additional cancer types.

In the first deal, Merck and Amgen expanded their collaboration to evaluate the efficacy and safety of talimogene laherparepvec, Amgen's investigational oncolytic immunotherapy, in combination with Merck's Keytruda in a Phase I trial for treating metastatic squamous cell carcinoma of the head and neck. In addition, the companies announced that a global, randomized Phase III trial evaluating the combination in patients with regionally or distantly metastatic melanoma is being initiated. As previously announced, the compounds are being studied in a Phase I trial in this patient population. Both immunotherapies are designed to modulate the immune system. Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response against cancer cells. Keytruda is a mAb that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

Merck also announced a collaboration with Tesaro Inc., an oncology-focused biopharmaceutical company,  to evaluate the combination of Tesaro's niraparib plus Merck's anti-PD1 therapy, Keytruda (pembrolizumab), in a Phase I/II clinical trial. The trial is planned to evaluate the preliminary safety and efficacy of niraparib plus Keytruda in patients with triple negative breast cancer or ovarian cancer. This trial will be conducted by Tesaro and Merck, through a subsidiary, and is expected to begin by the end of 2015.

Niraparib, an oral, selective inhibitor of PARP-1 and PARP-2. PARP, or poly (ADP-ribose) polymerase, is a DNA repair protein that restores single strand DNA breaks. By inhibiting PARP, certain cancer cells may be rendered unable to repair DNA damage, which can lead to cell death. A Phase 1/2 monotherapy study of niraparib was completed in patients with advanced solid tumors. Two Phase III trials are currently ongoing to evaluate a single oral dose of niraparib as a maintenance therapy for patients with ovarian cancer and as a treatment for patients with BRCA-positive breast cancer. A Phase II study designed to evaluate niraparib as a treatment for patients with ovarian cancer who have received prior therapies is also ongoing.

Merck & Co. Inc. and NanoString Technologies, Inc., a provider of life science tools for translational research and molecular diagnostic products, have formed a clinical research collaboration to develop an assay that will optimize immune-related gene expression signatures and evaluate the potential to predict benefit from Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), in multiple tumor types. The collaboration will use NanoString's nCounter Analysis System to optimize gene expression signatures as part of the clinical development program for Keytruda.

Merck & Co. Inc. and Dynavax Technologies Corporation also formed two clinical trial collaboration agreements to investigate the potential synergistic effect of combining immunotherapies from both companies' pipelines: Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), and its investigational anti-interleukin-10 (anti-IL-10) immunomodulator, MK-1966, with Dynavax's investigational toll-like receptor 9 (TLR9) agonist, SD-101.

SD-101, KEYTRUDA, and MK-1966 are immunotherapies designed to enhance the body's own defenses in fighting cancer. SD-101 is designed to mediate anti-tumor effects by triggering both innate and adaptive immune responses, including the induction of high levels of Type 1 interferon to stimulate recruitment of T-cells. Keytruda is a humanized  mAb that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. MK-1966 is an investigational anti-IL-10 immunomodulator designed to neutralize the immune-suppressive environment for tumors. The collaboration includes multiple studies that will evaluate the safety and efficacy of combining SD-101 with Keytruda in patients with advanced melanoma; this Phase I1b/II, multicenter, open-label study is expected to be initiated in the second half of 2015. Other studies will evaluate the safety and efficacy of combining SD-101 with MK-1966 in patients with solid or hematological malignancies; this Phase 1 study is expected to be initiated in the second half of 2015.

SD-101 is a proprietary, second-generation, TLR9 agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase I/II oncology studies to assess its preliminary safety and activity.

MK-1966, an investigational anti-interleukin-10 (anti-IL-10) immunomodulator, is designed to neutralize the immune-suppressive environment for tumors. MK-1966 blocks the activity of IL-10 which is known to down modulate the immune activation that is needed to kill tumor cells in the tumor microenvironment. These effects include decrease in cytokine production, upregulation of T regulatory cell activity and downregulation of antigen presenting cell activity. Based on preclinical data, co-administration of an anti-IL-10 with a TLR9 agonist may provide clinical benefit in the treatment of certain cancers.

Merck is advancing a broad and fast-growing clinical development program for Keytruda with more than 100 clinical trials across more than 30 tumor types and enrolling more than 16,000 patients, both as a monotherapy and in combination with other therapies.

Novartis. Novartis added to its oncology portfolio with the acquisition of GlaxoSmithKline's (GSK) oncology business as part of a three-part acquisition between the two companies, which further included the formation of a consumer healthcare joint venture and Novartis' divestment of its vaccine (excluding flu) vaccine business to GSK. Novartis highlighted and plans to highlight the strength of its expanded oncology portfolio in 21 medicines and 11 investigational compounds across more than 185 data presentations at the recent ASCO annual meeting and at the upcoming Congress of the European Hematology Association (EHA), which will be held June 11-14. Data will demonstrate advances in research in a variety of cancer types, including melanoma, lung, breast, kidney and blood cancers. Key data presentations show potential benefit of identifying tumor-specific biomarkers and combination treatment strategies for several commercial small molecules: Tafinlar (dabrafenib) and Mekinist (trametinib) for BRAF V600E mutated metastatic non-small cell lung cancer; Zykadia (ceritinib): in ALK+ NSCLC; and Afinitor (everolimus) for metastatic renal cell carcinoma and HER2+ breast cancer. On the biologics side, key pipeline candidates evolve around the development of chimeric antigen receptor T cell (CAR T) therapies in a variety of cancers including lymphoma, multiple myeloma, and pancreatic cancer.

Earlier this year, Novartis formed a major multiyear alliance with Aduro Biotech that is focused on the discovery and development of small-molecule cancer immunotherapies targeting the STING (Stimulator of Interferon Genes) pathway and has launched a new immuno-oncology research group led by cancer vaccine expert Glenn Dranoff, MD. Under its deal with Aduro, Novartis made an upfront payment of $200 million to Aduro and an initial equity investment in the company for $25 million, with a commitment for another $25 million equity investment at a future date. Aduro will lead commercialization activities and book sales in the US, with Novartis leading commercialization and recognizing sales in the rest of the world. The companies will share in profits in the US, Japan, and major European countries. Novartis will pay Aduro a royalty for sales in the rest of the world.STING is a signaling pathway that when activated is known to initiate broad innate and adaptive immune responses in tumors. Aduro's small-molecule cyclic dinucleotides (CDN's) have proven to generate an immune response in preclinical models that specifically attacks tumor cells. The addition of STING agonists adds to Novartis' portfolio of immunotherapies that includes chimeric antigen receptor T-cell (CART) technology and checkpoint inhibitors. Currently the CART program, CTL019, is in Phase II clinical trials and checkpoint inhibitors targeting PD1, LAG3, and TIM3 are expected to enter the clinic in mid-2015.

Pfizer. On the small-molecule side at the annual meeting of ASCO, Pfizer Inc. reported positive results for its breast cancer drug, Ibrance (palbociclib), in combination with fulvestrant in extending progression-free survival (PFS) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer whose disease has progressed during or after endocrine therapy. Ibrance (palbociclib) is an oral inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 CDKs 4 and 6 are key regulators of the cell cycle that trigger cellular progression. Ibrance is indicated in the US for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

In the area of immuno-oncology, earlier this year, Merck KGaA and Pfizer initiated a Phase III clinical trial for the companies' investigational cancer immunotherapy, avelumab, to treat non-small cell lung cancer. The drug is part of the immunotherapy alliance that Pfizer and Merck KGaA formed in November 2014. Avelumab 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 engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity. In November, 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab. The clinical trial will study avelumab, compared with docetaxel, in patients with Stage IIIb/IV non-small cell lung cancer who have experienced disease progression after receiving a prior platinum-containing doublet therapy. The immuno-oncology alliance between the companies will jointly develop and commercialize avelumab and advance Pfizer's PD-1 antibody. The companies will collaborate on up to 20 high priority immuno-oncology clinical development programs, including combination trials, many of which are expected to commence in 2015.

In 2014, Pfizer Inc. and Cellectis, a French company specializing in immunotherapy, formed a global strategic collaboration to develop chimeric antigen receptor T-cell (CAR-T) immunotherapies in the field of oncology directed at select targets. Cellectis' CAR-T platform technology provides a proprietary, allogeneic approach (using engineered T-cells from a single donor for use in multiple patients) to developing CAR-T therapies that is distinct from other autologous approaches (engineering a patient's own T-cells to target tumor cells). Under the agreement, Pfizer has exclusive rights to pursue development and commercialization of CAR-T therapies, in the field of oncology, directed at a total of 15 targets selected by Pfizer. Both companies will work together on preclinical research, and Pfizer will be responsible for the development and potential commercialization of any CAR-T therapies for the Pfizer-selected targets. In addition, the agreement provides for a total of 12 targets selected by Cellectis. Both companies will work together on preclinical research on four Cellectis-selected targets, and Cellectis will work independently on eight additional targets. Cellectis will be responsible for clinical development and commercialization of CAR-T therapeutics for the Cellectis-selected targets. Pfizer has right of first refusal to the four Cellectis-selected targets. Cellectis will receive an upfront payment of $80 million, as well as funding for research and development costs associated with Pfizer-selected targets and the four Cellectis-selected targets within the collaboration. Cellectis is eligible to receive development, regulatory and commercial milestone payments of up to $185 million per Pfizer product. Cellectis is also eligible to receive tiered royalties on net sales of any products that are commercialized by Pfizer.

Roche. Roche's oncology drugs are among company's top-selling drugs with three anti-cancer biologics representing the company's top-selling drugs in 2014: MabThera/Rituxan (rituximab), 2014 sales of CHF 6.9 billion ($7.39 billion); Avastin (bevacizumab) with sales of CHF 6.417 billion ($6.87 billion); and Herceptin (trastuzumab), with sales of CHF 6.275 billion ($6.719 billion). In 2014, he company's pharmaceutical sales were driven by growth of medicines for HER2-positive breast cancer (+ 20%), as well as the cancer drug Avastin (bevacizumab) (+ 6%). New products, Perjeta (pertuzumab) and the antibody drug conjugate, Kadcyla (trastuzumab emtansine), both for treating HER2-positive breast cancer, although having modest sales, made a contribution to growth in 2014. At the recent ASCO meeting, Roche highlighted positive date for its biologic anti-cancer drug, Gazyva/Gazyvaro (obinutuzumab) plus bendamustine followed by Gazyva/Gazyvaro alone for treating indolent non-Hodgkin's lymphoma. Roche also highlighted progress among several small-molecule drug candidate, including the MEK inhibitor cobimetinib in combination with Roche's Zelboraf (vemurafenib) for treating previously untreated BRAF V600 mutation-positive advanced melanoma.

At the annual ASCO meeting, Roche reported positive results that Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) and docetaxel chemotherapy given prior to surgery reduced the risk of disease getting worse and increased the time people lived without their cancer returning compared to Herceptin and chemotherapy in people with HER2-positive early-stage breast cancer (eBC). In 2013, the the FDA granted approval of the Perjeta regimen for neoadjuvant treatment in people with high-risk, HER2-positive eBC. Roche recently submitted a marketing authorization application to the European Medicines Agency (EMA) for the Perjeta regimen as a neoadjuvant treatment for people with HER2-positive eBC.

In the area of immune-oncology, earlier this month, Amgen and Roche formed a collaboration on a Phase Ib study to evaluate the safety and efficacy of talimogene laherparepvec, Amgen's investigational oncolytic immunotherapy, in combination with Roche's investigational anti-PDL1 therapy, atezolizumab (also known as MPDL3280A), in patients with triple-negative breast cancer and colorectal cancer with liver metastases.

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells. Atezolizumab is an investigational monoclonal antibody designed to interfere with the PD-L1 protein. The rationale for combining these two investigational agents is to activate an anti-tumor immune response with talimogene laherparepvec and to block inhibitory T cell checkpoints with atezolizumab, to potentially increase the anti-tumor activity relative to each agent alone.

Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

Atezolizumab is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.