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8-K – Current report

On July 21, 2014, Advaxis, Inc. ("Advaxis") and MedImmune, LLC ("MedImmune"), the global biologics research and development arm of AstraZeneca, entered into a Clinical Trial Collaboration Agreement (the "Agreement") pursuant to which the parties intend to initiate Phase I and Phase II clinical trials in the United States to evaluate the safety and efficacy of MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with Advaxis’s investigational Lm-LLO cancer immunotherapy, ADXS-HPV, as a combination treatment for patients with advanced, recurrent or refractory human papillomavirus (HPV) associated cervical cancer and HPV-associated head and neck cancer (Filing 8-K , Advaxis, JUL 24, 2014, View Source [SID:1234500643]). A joint steering committee, to be composed of equal numbers of Advaxis and MedImmune representatives, will be responsible for various matters associated with the clinical trials, including approving protocols for the trials, as well as reviewing and monitoring the progress of the trials.

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MedImmune will be responsible for providing MEDI4736 for the clinical trials at no cost. Advaxis will be the sponsor of the clinical trials and be responsible for the submission of all regulatory filings to support the trials, the negotiation and execution of the clinical trial agreements associated with each study site, and the packaging and labelling of the Advaxis and MedImmune product candidates to be used in the clinical trials and the costs associated therewith.

For a period beginning upon the completion of the clinical trials and the receipt by MedImmune of the last final report for the trials and ending one hundred twenty (120) days thereafter (unless extended), MedImmune will be granted first right to negotiate in good faith in an attempt to enter into an agreement with Advaxis with respect to the development, regulatory approval and commercialization of ADXS-HPV and MEDI4736 to be used in combination with each other for the treatment or prevention of cancer. Neither party is obligated to enter into such an agreement. In the event the parties do not enter an agreement and Advaxis obtains regulatory approval for ADXS-HPV in combination with any PD-1 antibody or PD-L1 antibody, Advaxis shall pay MedImmune a royalty obligation and one-time payment.

All intellectual property rights made, conceived or generated through the clinical trials that relate solely to a MedImmune development product shall be owned solely by MedImmune. All intellectual property rights made, conceived or generated through the clinical trials that relate solely to an Advaxis development product shall be owned solely by Advaxis. All intellectual property rights made, conceived or generated through the clinical trials that relate to the combination of one or more MedImmune development product and one or more Advaxis development product shall be jointly owned by MedImmune and Advaxis; provided, however that in the event the parties do not enter into a clinical development and commercialization agreement, Advaxis will not exploit, commercialize or license the joint inventions, except for the performance of its obligations under the Agreement. MedImmune has the sole right to prosecute and enforce all patents and other intellectual property rights covering all joint inventions and all associated costs will be shared by the parties.

The Agreement shall remain in effect until the earlier of (i) permitted termination, (ii) the parties entering into a clinical development and commercialization agreement or expiration of the negotiation period (unless extended), except with respect to rights that survive termination. Either party may terminate the Agreement upon thirty (30) days written notice upon material breach of the other party, unless the breach is cured in such period or reasonable actions to cure the breach are initiated and pursued (if the breach is not capable of being cured during the 30-day notice period). In addition, either party may terminate the Agreement immediately if the party determines in good faith that the trials may unreasonably affect the safety of trial subjects.

Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Announce Strategic Immuno-Oncology Collaboration in Japan, South Korea and Taiwan

On July 23, 2014 Bristol-Myers Squibb and Ono Pharmaceutical signed a strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens to help address the unmet medical needs of patients with cancer in Japan, South Korea and Taiwan (Press release Bristol-Myers Squibb, JUL 23, 2014, View Source [SID:1234500645]). As part of the agreement, Bristol-Myers Squibb and Ono will jointly develop and commercialize Opdivo (nivolumab) and Yervoy (ipilimumab) across a broad range of tumor types.

Opdivo is a PD-1 immune checkpoint inhibitor approved in Japan for the treatment of patients with unresectable melanoma, making it the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world, and is being developed in multiple tumor types in more than 35 clinical trials. Yervoy, a CTLA-4 immune checkpoint inhibitor, is approved in Taiwan for the treatment of patients with advanced melanoma who have received prior therapy, and is in late-stage development as a potential treatment option for melanoma, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in Japan. The agreement includes three additional early-stage clinical immuno-oncology assets from Bristol-Myers Squibb: lirilumab, an antibody that blocks the KIR receptor on natural killer cells, urelumab, an agonist of the CD137 co-stimulatory receptor, and BMS-986016, a LAG3 immune checkpoint inhibitor.

Bristol-Myers Squibb and Ono will jointly pursue development of monotherapy and combination regimens, with Opdivo as the foundational therapy in Japan, South Korea and Taiwan, and leverage global clinical trials by including patients from the three countries.

“Bristol-Myers Squibb’s collaboration with Ono supports our goal to maximize the full potential of our immuno-oncology portfolio for patients worldwide,” said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. “This collaboration combines our leadership in immuno-oncology with both companies’ experience and capabilities in Asia, and strengthens our long-standing relationship with Ono.”

“Our collaboration with Bristol-Myers Squibb strengthens our ability to further enhance the potential of Opdivo, for which Ono recently received manufacturing and marketing approval in Japan as the first PD-1 inhibitor approved anywhere in the world,” said Gyo Sagara, President, Representative Director and CEO, Ono. “By pursuing the study of investigational combination regimens of immunotherapies with Bristol-Myers Squibb, we hope to bring a range of new therapeutic options to cancer patients.”

Under the terms of the agreement, Bristol-Myers Squibb and Ono will jointly develop and commercialize all collaboration products in Japan, South Korea and Taiwan. Development costs and commercial profits will be shared equally when Opdivo is used in combination with any Bristol-Myers Squibb compound (Yervoy, lirilumab, urelumab, BMS-986016). For a Bristol-Myers Squibb compound used as monotherapy, or two Bristol-Myers Squibb compounds used in a combination regimen, Bristol-Myers Squibb will fund the substantial majority of development costs and receive the substantial majority of commercial profits. When Opdivo is used as a single agent, Ono will fund the substantial majority of development costs and receive the substantial majority of commercial profits.

Prior to this announcement, Ono held exclusive rights to develop and commercialize Opdivo in Japan, South Korea and Taiwan while Bristol-Myers Squibb held such rights in the rest of the world, along with sole rights to develop and commercialize Yervoy, lirilumab, urelumab, and BMS-986016 worldwide. The trade name Opdivo has been proposed in the U.S. and other countries, but remains subject to health authority approval.

U.S. Food and Drug Administration Approves Gilead’s Zydelig® (idelalisib) for Relapsed Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma

On July 23, 2014 Gilead Sciences reported that the U.S. Food and Drug Administration (FDA) has approved Zydelig (idelalisib) 150 mg tablets for the treatment of three B-cell blood cancers (Press release Gilead Sciences, JUL 23, 2014, View Source [SID:1234500638]). Zydelig is indicated in combination with rituximab for patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy and as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. Accelerated approval was granted for FL and SLL based on overall response rate. Zydelig is a first-in-class inhibitor of PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells.

“Zydelig is a much needed new treatment option for appropriate patients with CLL and these indolent lymphomas who have experienced relapses and have limited, if any, treatment options,” said Bruce Cheson, MD, Professor of Medicine, Head of Hematology and Director of Hematology Research at Lombardi Comprehensive Cancer Center at Georgetown University, and a principal investigator on the Zydelig pivotal Phase 3 trial in CLL. “In clinical studies among patients with relapsed CLL, FL and SLL, Zydelig produced strong responses, including a significant improvement in progression-free survival in CLL. I believe it helps fill a significant unmet need for these patients.”

Over 200,000 Americans are living with CLL, FL or SLL, slow-growing incurable blood cancers that can lead to life-threatening complications such as anemia, serious infection and bone marrow failure requiring treatment. Relapse commonly occurs after initial chemoimmunotherapy and many patients with relapsed CLL, FL or SLL are unable to tolerate chemotherapy, which may limit their treatment options.

“Gilead is committed to the development of novel cancer therapies and we are proud to have this opportunity to make a difference in the lives of people living with these cancers,” said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. “We extend our thanks to the many physicians and patients who participated in Zydelig clinical trials, and are now focused on making this medicine available to patients as expeditiously as possible.”

The product’s approval in CLL is supported primarily by data from a randomized, placebo-controlled Phase 3 trial (Study 116) of Zydelig plus rituximab in 220 patients with relapsed CLL who were not able to tolerate standard chemotherapy. Study 116 was stopped early in October 2013 by an independent Data Monitoring Committee due to a highly statistically significant benefit in progression-free survival (PFS) in the Zydelig arm as compared to those receiving rituximab alone (hazard ratio = 0.18 (95 percent CI: 0.10, 0.32), p<0.0001). Median PFS was not reached in the Zydelig plus rituximab arm (95 percent CI: 10.7 months, NR) and was 5.5 months in the placebo plus rituximab arm (95 percent CI: 3.8, 7.1). The FDA granted Zydelig a Breakthrough Therapy designation for relapsed CLL, a designation granted to drug candidates that may offer major advances in treatment over existing options. Zydelig’s accelerated approval in FL and SLL, two types of indolent non-Hodgkin lymphoma, is supported by data from a single-arm Phase 2 study (Study 101-09) of Zydelig monotherapy in patients refractory to rituximab and alkylating-agent-containing chemotherapy (FL: n=72; SLL: n=26). In the study, Zydelig achieved an overall response rate of 54 percent (range: 42-66 percent) and 58 percent (range: 37-77 percent), respectively, in FL and SLL patients. Of the responses seen in FL patients, 8 percent (n=6) were complete responses; all 15 responses in SLL patients were partial responses. The median duration of response was 11.9 months in SLL patients (range: 0.0, 14.7 months) and median duration of response was not reached in FL patients (range: 0.0, 14.8 months). Improvement in patient survival or disease related symptoms has not been established in these indications. Results of Study 116 and Study 101-09 were published in The New England Journal of Medicine in March 2014.

MonoSol Rx Enters Into Exclusive Licensing Agreement with Galena Biopharma for Zuplenz® Oral Soluble Film

On July 22, 2014 MonoSol Rx, the developer of PharmFilm drug delivery technology, reported that it has licensed Zuplenz (ondansetron) to Galena Biopharma, a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major unmet medical needs to advance cancer care (Press release, MonoSol Rx, JUL 22, 2014, View Source [SID:1234508915]). Zuplenz is an oral soluble film (OSF) for the prevention of chemotherapy-induced, radiotherapy-induced, and postoperative nausea and vomiting.

The licensing agreement includes an undisclosed upfront payment from Galena, as well as double digit royalty payments from sales of Zuplenz. Zuplenz is the first oral soluble lingual film product approved by the U.S. Food and Drug Administration (FDA) as a prescription medication, based on MonoSol Rx’s proprietary PharmFilm technology.

Keith J. Kendall, Co-President and Chief Operating Officer of MonoSol Rx, remarked, "Partnering with Galena Biopharma to provide Zuplenz to patients in need further reinforces MonoSol Rx’s position as a leader in the oral soluble film pharmaceutical market. Through this partnership, we hope to empower supportive care providers with a more comfortable, easier-to-use formulation of ondansetron that addresses a significant unmet medical need, particularly among cancer patients. With the increased availability of Zuplenz, clinicians will be able to improve the level of care they provide by utilizing our innovative drug delivery technology to eliminate swallowing issues and discomfort associated with chemotherapy, radiotherapy, and surgery."

"We are pleased to be working with MonoSol Rx to offer Zuplenz to patients in need," said Mark J. Ahn, Ph.D., President and Chief Executive Officer of Galena Biopharma. "MonoSol Rx’s oral film delivery technology represents a substantive advancement in terms of ease of use and compliance for supportive care patients, where difficulty swallowing can be a major issue. Providing patients with an alternative solution for nausea and vomiting has long been a concept that oncologists and the general surgeon and oncology nurse communities have sought, and that we are eager to deploy."

Zuplenz is a unique formulation of ondansetron using MonoSol Rx’s proprietary PharmFilm technology, co-developed with partner APR Applied Pharma Research s.a. of Switzerland. It is based on a novel and proprietary oral drug delivery technology platform and consists of a polymeric OSF containing ondansetron. Once placed in the mouth, it dissolves in a few seconds, allowing the medication to be absorbed and delivered without water.

OBI Pharma Announces Completion of Patient Enrollment in Phase 2/Phase 3 Clinical Trial of OBI-822 Active Immunotherapy for Metastatic Breast Cancer

On July 22, 2014 OBI Pharma reported hat it has completed patient enrollment in its Phase 2/3 clinical trial evaluating the safety and efficacy of its lead compound, OBI-822, an active immunotherapy for the treatment of metastatic breast cancer (Press release OBI Pharma, JUL 22, 2014, View Source;fn=news_content&no=11 [SID:1234501492]).

"Completing enrollment in the Phase 2/3 clinical trial is a major milestone in the development of OBI-822", said Michael N. Chang, Ph.D., Chairman of the Board of OBI. "Our next target is a global phase 3 trial – now that there is a current IND with the US FDA and an IND application already submitted in China. We look forward to the results of this trial being confirmed once the course of treatment is completed in all enrolled patients early next year."

"The cancer active immunotherapy, OBI-822 guides the immune system to attack breast cancer cells, with minimal side effects, [as observed in the OBI’s Phase 1 and Phase 2/3 clinical trials]" said Amy Huang, General Manager of OBI. "OBI-822’s anti-cancer potential goes beyond breast cancer. All tumor cells expressing Globo series glycan (Globo H, SSEA-3 and SSEA-4) are possible treatment targets for OBI-822. According to the latest research findings reported by Taiwan’s Academia Sinica, the Globo H vaccine can potentially treat up to 16 different types of cancer. In fact, OBI Pharma and Mackay Memorial Hospital jointly initiated a Phase 2 ovarian cancer trial in November 2013 which is currently on-going."

Earlier clinical results
Phase 1 studies of the OBI-822/OBI-821 combination conducted at MSKCC induced both IgM and IgG responses demonstrating that Globo H-specific antibodies can effectively induce complement-mediated cytotoxicity as well as antibody-dependent cytotoxicity. The most commonly observed side effects in the Phase I clinical studies of metastatic breast and prostate cancers were mild local skin reactions and minor flu-like symptoms.

Clinical Study Design
The Phase 2/3 randomized controlled trial (RCT) was initiated in December, 2010 with an enrollment target of 342 subjects. The study enrolled female subjects with metastatic breast cancer who achieved stable disease (SD), partial response (PR), or complete response (CR) after at least 1 regimen of anticancer therapy. Subjects were randomized to receive either active treatment (OPT‐822/OPT‐821) plus cyclophosphamide or control (PBS) plus cyclophosphamide in a 2:1 allocation.