Genmab Announces New Phase III Combination Study of Daratumumab in Frontline Multiple Myeloma

On November 10, 2014 Genmab reported that the French Intergroup of Myeloma (IFM) in collaboration with Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Biotech, Inc. (Janssen) plans to start an additional Phase III study of daratumumab in frontline multiple myeloma (Press release Genmab, NOV 10, 2014, View Source [SID:1234500941]). The study (MMY3006) will compare daratumumab in combination with bortezomib, thalidomide and dexamethasone (VTD) to bortezomib, thalidomide and dexamethasone alone as front line treatment for patients who are candidates for stem cell transplantation (SCT). The study is planned to start in Q2 2015. The first Phase III study in front line multiple myeloma was announced in July and is expected to start towards the end of this year, with the two other Phase III front line studies to start next year. In total today’s news is the fifth daratumumab Phase III study to be announced.

“The daratumumab development plan is progressing at a very fast pace and we are very pleased to announce yet another Phase III study. The expansive development program covers different stages of multiple myeloma, and this will be the third Phase III study to enroll patients newly diagnosed with the disease,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

(Filing, 20-F, Rosetta Genomics, NOV 9, 2014, View Source [SID:1234505276])

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Scientific Data on PYK2 Inhibition by VS-4718 in Multiple Myeloma Published in the Journal Blood

On November 7, 2014 Verastem reported that a paper, titled "PYK2 Promotes Tumor Progression in Multiple Myeloma," has been published in Blood (2014 Oct 23;124(17):2675-86), a peer-reviewed medical journal published by the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release Verastem, NOV 7, 2014, View Source;p=RssLanding&cat=news&id=1987281 [SID:1234500939]).

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"These data demonstrate that PYK2 is a promising therapeutic target in multiple myeloma," said Jonathan Pachter, Ph.D., Verastem Head of Research. "These results build upon prior scientific findings demonstrating the activity of dual FAK/PYK2 inhibitors across multiple types of cancer and support the ongoing clinical development of VS-4718."

The paper describes the finding that patients with multiple myeloma have a higher expression of proline-rich tyrosine kinase 2 (PYK2), a member of the focal adhesion kinase (FAK) family, compared to healthy individuals, and that PYK2 plays a tumor-promoting role in myeloma progression. The FAK family is composed of just two members, FAK and PYK2, which are highly homologous. In the published study, it was demonstrated that inhibition of PYK2 led to reduction of myeloma tumor growth in vivo as well as decreased cell proliferation, cell cycle progression, and adhesion ability in vitro. In contrast, overexpression of PYK2 was shown to promote the malignant phenotype, as evidenced by enhanced tumor growth and reduced survival. The paper further describes how administration of Verastem’s FAK/PYK2 inhibitor, VS-4718, effectively inhibited myeloma cell growth in both in vitro and in vivo models.

"In addition to this work recently published by our collaborators at the Dana Farber Cancer Institute, we have been conducting further research and collaborating with scientific leaders to understand the potential of cancer stem cell inhibitors in hematological malignancies", continued Dr. Pachter. "We believe that inhibitors of FAK and PYK2, such as VS-4718, may be useful in the treatment of many types of cancer, particularly where there is minimal residual disease with enrichment of cancer stem cells following chemotherapy. We and our collaborators will be presenting additional research at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) in December."

"VS-4718 is currently being evaluated in a Phase 1 dose escalation clinical trial in patients with advanced solid tumors," said Robert Forrester, President and Chief Executive Officer of Verastem. "A new Phase 1 trial of VS-4718 in hematological malignancies is currently planned to begin in the first quarter of 2015."

(Press release, CanTx, NOV 6, 2014, View Source [SID:1234505853])

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MacroGenics Announces Pre-clinical Data to be Presented at ASH 2014 Annual Meeting

On November 6, 2014 MacroGenics reported that pre-clinical data on MGD011, a humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART) protein, will be highlighted in a poster presentation at the 56th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), to be held December 6-9, 2014 in San Francisco, CA (Press release MacroGenics, NOV 6, 2014, View Source [SID:1234501246]).

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MGD011 is designed to redirect T-cells to eliminate CD19-expressing cells found in many hematological malignancies and has been engineered to address half-life challenges posed by other programs targeting CD19 and CD3. Moreover, MGD011 and other DART molecules are manufactured using a conventional antibody platform without the complexity of having to genetically modify T cells from individual patients as required by approaches such as chimeric antigen receptor (CAR) T cells. MGD011 has a modified Fc domain, which allows for extended pharmacokinetic properties and convenient dosing at a once-a-week or longer interval. It is one of two new oncology-based DART candidates for which MacroGenics intends to initiate clinical studies in 2015.

"This represents another important milestone for our DART platform," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "CD19-targeted therapies have generated much excitement, and, based on our pre-clinical data, we believe that MGD011 has great potential in the treatment of patients with certain types of hematological malignancies. We look forward to initiating clinical development in 2015."