On March 6, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN), a global biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold announced on December 27, 2016 on phase 1 trials of vadastuximab talirine (SGN-CD33A; 33A) in acute myeloid leukemia (AML) (Press release, Seattle Genetics, MAR 6, 2017, View Source [SID1234518019]).

“The clinical hold on our early-stage vadastuximab talirine clinical trials has been resolved through a comprehensive analysis of the clinical data from over 300 patients treated to date, evaluation by an independent committee of clinical experts, collaborative interactions with the FDA, and protocol amendments designed to further enhance patient safety,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “We will resume two phase 1 trials in AML and plan to initiate a randomized phase 2 trial during 2017 evaluating vadastuximab talirine in combination with standard of care chemotherapy in frontline, younger AML patients. In addition, we are continuing to enroll our ongoing phase 3 randomized CASCADE trial in frontline older AML patients and our phase 1/2 trial in frontline high-risk myelodysplastic syndrome (MDS).”

Seattle Genetics will resume two phase 1 trials of vadastuximab talirine. The first is combination treatment with standard of care, or 7+3, chemotherapy in newly diagnosed younger AML patients and the second is monotherapy and combination treatment with hypomethylating agents in both newly diagnosed and relapsed AML patients. Seattle Genetics will not resume the phase 1/2 trial of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant AML patients given the challenges of developing therapies in this specific setting. The company’s randomized global phase 3 CASCADE trial in frontline older AML and phase 1/2 trial in frontline MDS were not placed on clinical hold and have continued to enroll patients. Planned studies include a randomized phase 2 trial of vadastuximab talirine in combination with 7+3 chemotherapy in frontline younger AML patients. Going forward, additional risk mitigation measures will be implemented in all vadastuximab talirine studies, including revised eligibility criteria and stopping rules for veno-occlusive disease (VOD).

About Vadastuximab Talirine
Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ proprietary ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its potent cell-killing PBD agent upon internalization into CD33-expressing cells.
Vadastuximab talirine was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.

On March 6, 2017 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform, reported that a set of ex vivo and in vivo data informing the trial design of a first-in-patient clinical trial for PRS-343, a first-in-class 4-1BB/HER2 bispecific, will be presented in a poster session at the 2017 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) to be held in Washington D.C., April 1 – 5, 2017 (Press release, Pieris Pharmaceuticals, MAR 6, 2017, View Source [SID1234518017]). PRS-343 binds to 4-1BB (CD137) on T cells and HER2 on tumor cells, producing tumor-targeted immune activation.

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Further details include:

Poster Number : 16

Title : Preclinical toxicology and pharmacology for the 4-1BB/HER2 bispecific PRS-343: A first-in-class costimulatory T cell engager.

Date and Time : Tuesday April 4, 2017, 8:00 AM – 12:00 PM

Location : Walter E. Washington Convention Center, Halls A-C, Poster Section 27
About PRS-343:
PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes (TILs), and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

On March 6, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported updated results from the ongoing, Phase 2 trial of tipifarnib, a selective inhibitor of farnesyl transferase, and additional preclinical data in HRAS mutant squamous cell carcinomas of the head and neck (SCCHN) (Press release, Kura Oncology, MAR 6, 2017, View Source [SID1234518010]). The data were presented today at the 15th International Congress on Targeted Anticancer Therapies (TAT 2017) in Paris, France.

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This update on the patients in the first stage of the second cohort of the Phase 2 clinical trial in HRAS mutant tumors reported that, as of February 28, 2017, the two patients with HRAS mutant SCCHN with objective responses remain on study and are currently at treatment cycle 19 and cycle 12. Among the five patients with HRAS mutant salivary gland cancer, although no objective responses were observed, three patients experienced disease stabilization and were on study for 9, 10 and 14 cycles. In addition, tipifarnib was generally well tolerated with adverse events consistent with its known safety profile.

"The durability of the responses we have observed with tipifarnib is compelling considering the setting of relapsed and/or refractory SCCHN," said Alan L. Ho, M.D., Ph.D., a medical oncologist at Memorial Sloan Kettering Cancer Center and a lead investigator on the study. "These data reinforce the relevance of testing for HRAS mutations in these patients."

"We are very encouraged by the durable responses we have observed in patients with relapsed and/or refractory HRAS mutant SCCHN who are treated with tipifarnib," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "The two patients with partial responses have now been on treatment with tipifarnib for more than 16 months and 10 months, respectively. Recruitment of patients with SCCHN has become more challenging in the United States with the approval of immune therapy agents. To facilitate enrollment in the second stage of our trial we are adding additional clinical sites in Western Europe and Asia, and are working with third party laboratories to facilitate HRAS screening. We anticipate that additional results from this ongoing Phase 2 trial of tipifarnib in HRAS mutant SCCHN will be available during the second half of 2017."

Dr. Ho’s slide presentation will be available at View Source

On March 6, 2017 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that Phase 1 clinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), were presented during a plenary session at the 15th International Congress on Targeted Anticancer Therapies (TAT 2017) taking place in Paris, France, March 6 – 8 (Press release, Infinity Pharmaceuticals, MAR 6, 2017, View Source [SID1234518009]). A Phase 1 clinical study is ongoing to explore the safety and activity of IPI-549 both as a monotherapy and in combination with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors. IPI-549 is believed to be the only selective PI3K-gamma inhibitor in clinical development.

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"The TAT congress has become a leading conference for Phase 1 clinical studies in oncology, so it is an honor to be invited to participate in a plenary session to discuss our progress with IPI-549 at this year’s congress," commented Claudio Dansky Ullmann, M.D., senior vice president, clinical development at Infinity.

Today’s presentation at TAT 2017 included updated Phase 1 data from 12 patients enrolled in the monotherapy dose-escalation phase of the ongoing study. The presentation, "A Phase 1/1b, First-in-Human Study of IPI-549, a PI3K-Gamma Inhibitor and Myeloid Targeting Agent, as Monotherapy and in Combination with Nivolumab in Patients with Advanced Solid Tumors," was given by Anthony Tolcher, M.D., FRCP(C), clinical director at South Texas Accelerated Research Therapeutics, an investigator for the Phase 1 study and the recipient of the TAT 2016 Honorary Award Invited Lecture.

"Based on the experience of patients in my clinic, I am encouraged about the potential of IPI-549, and the data to date suggest that the safety, pharmacokinetics and pharmacodynamics of monotherapy treatment appear favorable," stated Dr. Tolcher. "IPI-549 holds the promise of offering a unique approach for enhancing the body’s anti-tumor immune response, and I look forward to continuing to participate in this Phase 1 clinical study."

Additionally, IPI-549 was discussed today during the TAT 2017 Honorary Award Invited Lecture, "Immunologic Checkpoint Blockade: Exploring Combinations and Mechanisms," which was given by Jedd Wolchok, M.D., Ph.D., Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK), as well as Associate Director of the Ludwig Center for Cancer Immunotherapy and Director of the Parker Institute for Cancer Immunotherapy, both at MSK. Dr. Wolchok serves as the lead investigator for the Phase 1 clinical study of IPI-549. He is also an author on the recently published Nature paper which described that the presence of suppressive myeloid cells is critical in tumor resistance to checkpoint inhibitors and targeting PI3K-gamma in these cells with IPI-549 is able to help overcome this resistance.1

"This is an exciting time in the field of immuno-oncology. New immunotherapies, such as checkpoint inhibitors, underscore the progress we have made in the treatment of various cancers. Even so, we are always exploring new avenues of investigation that we hope will benefit even more patients," stated Dr. Wolchok. "IPI-549 is one of the newer and potentially promising immunotherapies in clinical development. Our research suggests IPI-549 could offer a unique way to both enhance the activity of checkpoint inhibition in sensitive tumors, as well as to overcome tumor resistance to checkpoint inhibition."

IPI-549 Poster Presentation at Upcoming AACR (Free AACR Whitepaper) Annual Meeting 2017
Last week, Infinity announced that updated Phase 1 data for IPI-549 will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 taking place in Washington, D.C. April 1 – 5. Details of the presentation are as follows:
Poster presentation time: Tuesday, April 4, 2017, 8:00 a.m. – 12:00 p.m. ET
Title: IPI-549-01 – A Phase 1/1b, First-in-Human Study of IPI-549, a PI3K-Gamma Inhibitor, as Monotherapy and in Combination with Nivolumab in Patients with Advanced Solid Tumors
Abstract number: CT089
Lead author: Jedd Wolchok, M.D., Ph.D., Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK), as well as Associate Director of the Ludwig Center for Cancer Immunotherapy and Director of the Parker Institute for Cancer Immunotherapy, both at MSK
Location: Convention Center, Halls A-C, Poster Section 33

Due to AACR (Free AACR Whitepaper) embargo policies, the data presented today at TAT 2017 will be made available during the AACR (Free AACR Whitepaper) Annual Meeting 2017.

About the IPI-549 and the Ongoing Phase 1 Study
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical tumor models.1,2 As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in patients with advanced solid tumors.3 The study includes monotherapy and combination dose-escalation phases, in addition to a monotherapy expansion cohort and combination expansion cohorts. Overall, the study is expected to enroll approximately 175 patients.

The expansion cohorts evaluating IPI-549 plus Opdivo will include patients with non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN). There is a great need for additional treatment options for the growing number of patients living with these types of cancers, which account for more than 17 percent of all new cancer cases in the U.S.4,5 Additionally, patients enrolled in the combination expansion cohorts represent a difficult-to-treat population, as they must have demonstrated initial resistance or subsequently develop resistance to a PD-1 or PD-L1 therapy immediately prior to enrolling in the study.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.