On November 4, 2015 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that Janssen Biotech, Inc. has dosed the first patient in a clinical trial evaluating subcutaneous (SC) delivery of daratumumab with Halozyme’s proprietary ENHANZE technology in multiple myeloma (Press release, Halozyme, NOV 4, 2015, View Source [SID:1234507946]).

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Daratumumab is an investigational human monoclonal antibody that targets CD38 on the surface of multiple myeloma cells and is in clinical development by Janssen using the intravenous route of administration. Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. Multiple myeloma is the third most common blood cancer in the United States (U.S.), following only leukemia and lymphoma. In the U.S., approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in 2015. Globally, it is estimated that 114,251 people will be diagnosed and 80,019 will die from the disease.

The Janssen Phase 1b clinical trial will evaluate the safety, pharmacokinetics and antitumor activity of a daratumumab by the subcutaneous route of administration in approximately 128 patients with relapsed or refractory multiple myeloma.

"We believe the transition from an IV to subcutaneous formulation has the potential to provide benefits to patients and health care professionals, including reduced administration time," said Dr. Helen Torley, president and CEO of Halozyme. "We are pleased to partner with Janssen to bring these potential benefits to multiple myeloma patients through the development of daratumumab using our proprietary rHuPH20 platform."

Halozyme’s ENHANZE technology is based on a proprietary recombinant human enzyme rHuPH20 that targets hyaluronan, a glycosaminoglycan, which is a chain of natural sugars found throughout the body and as a component of the extracellular matrix, to aid in the dispersion and absorption of other injected therapeutic drugs.

Halozyme Collaboration with Janssen Biotech, Inc.

In December 2014, Halozyme and Janssen entered into a collaboration and license agreement. Under the terms of the agreement, Halozyme has granted to Janssen a worldwide license to develop and commercialize products for up to five targets, combining rHuPH20 with Janssen’s proprietary compounds. CD38, which is targeted by daratumumab, is the first of these five targets. Halozyme received an initial payment of $15 million, and is eligible to receive additional payments upon Janssen’s achievement of specified development, regulatory and sales-based milestones, totaling up to $566 million. Halozyme is also entitled to royalty payments based on net sales of products using the ENHANZE technology. Under the collaboration, Janssen will also obtain access to Halozyme’s expertise in developing and applying rHuPH20 to Janssen targets and will obtain a worldwide, exclusive license to develop and commercialize product combinations of rHuPH20 and Janssen target compounds resulting from the collaboration.

About ENHANZE

ENHANZE is Halozyme’s proprietary drug delivery platform based on the Company’s patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections.

On November 4, 2015 Merck and Pfizer reported the initiation of an international Phase III study of the investigational cancer immunotherapy avelumab* in a treatment naive advanced NSCLC setting (Press release, Merck KGaA, NOV 4, 2015, View Source [SID:1234507936]). The study, JAVELIN Lung 100, is designed to assess the safety and efficacy of avelumab, compared with platinum-based doublet chemotherapy in patients with late-stage NSCLC who have not previously received any treatment for their systemic lung cancer. Avelumab (previously known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody that potentially uses the body’s own immune system to fight cancer.

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The Phase III study is an open-label, multicenter, randomized clinical trial, in which patients with recurrent or Stage IV PD-L1+ NSCLC will receive either avelumab or the investigator’s choice of platinum-based chemotherapy, depending on the patient’s histology (either squamous or non-squamous), as first-line treatment. Patients will be pre-screened for PD-L1+ status using an immunohistochemistry-based companion diagnostic test.

The study expects to enroll approximately 420 patients across more than 240 sites in Africa, America (North and South), Asia and Europe. Clinical trials in North America on behalf of Merck will be conducted by EMD Serono, the company’s US and Canadian biopharmaceutical business.

"Through this Phase III trial, we hope to gain a better understanding of avelumab as a potential first-line treatment for non-small cell lung cancer – a prevalent and devastating disease," said Dr. Luciano Rossetti, Head of Global Research & Development at Merck’s biopharma business. "We are working to help patients with this challenging cancer and will continue to develop our NSCLC program by evaluating avelumab as a potential monotherapy and in combination with our extensive portfolios of approved and investigational oncology therapies."

The primary endpoint of the study is progression-free survival in patients with PD-L1+ tumors. Secondary endpoints include progression-free survival in patients with strongly PD-L1 positive (PD-L1++) tumors, overall survival, objective response rate, quality of life, tolerability and safety in patients treated with avelumab versus investigator-choice chemotherapy. This is the second randomized Phase III study of avelumab in NSCLC initiated in just over six months; the first study was initiated in April 2015 and is evaluating avelumab in patients whose disease has progressed after receiving a platinum-containing doublet chemotherapy compared with docetaxel.

"There is great promise for the use of immunotherapy in the treatment of non-small cell lung cancer and this new trial underscores our continuing commitment to investigating potential immune-based treatment options for this devastating disease," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology. "The clinical development program for avelumab continues to accelerate, and the initiation of this Phase III study represents another important achievement in 2015 for the alliance between Merck and Pfizer."

The clinical development program for avelumab now includes more than 1,400 patients who have been treated across more than 15 tumor types, including breast cancer, gastric/gastro-esophageal (GEJ) cancers, head and neck cancer, Merkel cell carcinoma, melanoma, NSCLC, ovarian cancer, renal cell carcinoma and urothelial (e.g., bladder) cancer.

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

References
1. American Cancer Society (2015). Global Facts & Figures Third Edition. Available from: www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf. Accessed October 2015.
2. American Cancer Society (2015). Lung Cancer (Non-Small Cell) [Fact sheet]. Available from: www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf. Accessed October 2015.
3. Mayo Clinic (2015). Cancer survival rate: what it means for your prognosis: View Source Accessed October 2015.

About Non-Small Cell Lung Cancer
Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women,1 responsible for more deaths than colon, breast and prostate cancer combined2. NSCLC is the most common type of lung cancer, accounting for 85 to 90 percent of all lung cancers2. The five-year survival rate for people diagnosed with late-stage lung cancer that has spread (metastasized) to other areas of the body is 4 percent.3

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