On October 25, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and QuantumLeap Healthcare Collaborative reported that a new treatment arm of the I-SPY2 TRIAL will include patritumab, an investigational anti-HER3 monoclonal antibody (Press release, Daiichi Sankyo, OCT 24, 2016, View Source [SID1234515984]).

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The I-SPY 2 TRIAL, sponsored by QuantumLeap Healthcare Collaborative (QLHC), is a standing phase 2 randomized, controlled, multicenter study with an innovative adaptive design aimed to rapidly screen and identify promising new treatments in specific subgroups of women with newly-diagnosed, locally-advanced breast cancer (Stage II/III). Patritumab in combination with standard trastuzumab (anti-HER2 monoclonal antibody) and paclitaxel (chemotherapy) treatment will be compared to standard therapy alone in the new treatment arm. Women with HER2+ breast cancer will be randomized to one of the treatment arms and receive treatment for 12 weeks prior to undergoing surgery to remove the breast tumor.

"The evaluation of patritumab in I-SPY 2 will inform our understanding of how agents with unique mechanisms of action, like HER3 inhibition, can combine with proven HER2 antagonists," said Melissa C. Paoloni, DVM, DACVIM-O, Executive Director of Clinical Activities, QuantumLeap Healthcare Collaborative, Sponsor of the I-SPY 2 TRIAL. "The results will help enhance the understanding of the treatment for patients with HER2-positive disease."

"Research suggests that the combination of a HER3 inhibitor with other inhibitors of HER family receptors may be a promising approach in treating breast cancer," said Dale E. Shuster, PhD, Executive Director, Clinical Development, Oncology, Daiichi Sankyo. "We are excited about the inclusion of patritumab in I-SPY 2 as this study is a prime example of how a unique scientific collaboration can aid in the evaluation of promising investigational agents for patients with unmet needs."

About I-SPY 2 Trial
The I-SPY 2 TRIAL (NCT01042379) (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) employs a unique adaptive trial design to match experimental therapies with patients, while testing whether adding investigational drugs to standard chemotherapy is better than standard chemotherapy alone in the neoadjuvant setting (prior to surgery).

The innovative adaptive design utilizes biological markers (biomarkers) from each woman to assign her to a particular investigational drug. The trial learns as it goes, as each patient’s response to a particular drug informs how the next patient will be assigned to a treatment arm. Drugs with a strong efficacy threshold for a particular patient group may "graduate" to a more focused phase 3 drug registration trial, while drugs found to be ineffective or with significant side effects are dropped from the trial quickly. This high efficacy bar (85% likelihood of success in a 300-person phase 3 trial) and rapid evaluation allow the trial to identify the right drug for the right patient in the most expeditious fashion.

The trial is conducted by a consortium that brings together the Food and Drug Administration (FDA), National Cancer Institute (NCI), pharmaceutical and biotech companies, leading academic medical centers, and patient advocates under its umbrella.

About Patritumab
Patritumab is an investigational fully human monoclonal antibody that inhibits HER3, a unique
member of the HER family that is abnormally activated in several types of cancer.1,2 To stimulate growth of a cancer cell, the HER3 receptor binds (dimerizes) with another HER family receptor such as EGFR or HER2. 1, 2 Preclinical evidence suggests that the combination of a HER3 inhibitor with other inhibitors of HER family receptors may be a promising therapeutic approach in treating certain cancers.2 In addition to inclusion in the I-SPY 2 TRIAL, a phase 2 study evaluating patritumab in previously-untreated recurrent or metastatic head and neck cancer is ongoing and enrolling patients.

About QuantumLeap Healthcare Collaborative
QuantumLeap Healthcare Collaborative, a non-profit foundation, was established in 2005 as a collaboration between medical researchers at University of California at San Francisco, and Silicon Valley entrepreneurs. QuantumLeap’s mission is to accelerate transfer of high-impact research in clinical processes and systems technology into widespread adoption so that patients and physicians can benefit from the research as soon as practicable. QuantumLeap provides operational, financial and regulatory oversight to I-SPY 2 and is also the sponsor of its companion phase 3 confirmatory trial, I-SPY 3. For more information, visit: View Source

On October 24, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that it has received notice from the U.S. Food and Drug Administration (FDA) that trials with investigational agents based on its LADD (Listeria-based immunotherapy construct) platform have been placed on partial clinical hold to pause new patient enrollment (Press release, Aduro BioTech, OCT 24, 2016, View Source [SID1234515981]). Patients currently receiving a LADD-based agent (except one currently identified patient, due to the presence of a pacemaker) are continuing to receive treatment, with several of these patients having been on study drug for six months or longer. The partial hold was initiated following notification to the FDA that a blood culture sample from an indwelling port of a metastatic pancreatic cancer patient who presented with gastrointestinal symptoms tested positive for Listeria, which is suspected to be CRS-207. The patient was administered intravenous antibiotics, subsequent blood cultures tested negative for Listeria, and the patient was reported to be doing well.

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Aduro is working with the FDA to lift the partial hold so as to resume new patient enrollment in its LADD clinical trials. The company is revising study protocols in accordance with feedback from the agency, including the modification of antibiotic administration following treatment, extended patient surveillance, and, as a pre-emptive measure, exclusion of patients who are on or will receive certain immune-suppressive treatments or who have certain prosthetic devices. Aduro will be providing proposed revisions to the protocols, patient consent forms, and investigator brochures to the agency later this week.

This partial hold does not impact any ongoing development of Aduro’s two other distinct platform technologies, STING pathway activators and B-select monoclonal antibodies.

On October 24, 2016 Agilent Technologies Inc. (NYSE: A) reported that its Dako PD-L1 IHC 22C3 pharmDx now has an expanded label approved by the U.S. Food and Drug Administration for use in determining PD-L1 expression status to inform treatment in metastatic non-small cell lung cancer (NSCLC) with KEYTRUDA (pembrolizumab) (Press release, Agilent, OCT 24, 2016, http://www.agilent.com/about/newsroom/presrel/2016/24oct-ca16033.html [SID1234515979]). This expanded intended use now allows the PD-L1 IHC 22C3 pharmDx test to detect PD-L1 expression in a broader range of patients — those with a PD-L1 tumor proportion score (TPS) of 1 percent or more.

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The FDA also announced on October 24 that KEYTRUDA is now approved for the first-line treatment of metastatic NSCLC patients whose tumors express high levels of PD-L1 (TPS of 50 percent or more) or for previously treated metastatic NSCLC patients whose tumors express PD-L1 (TPS of 1 percent or more).

This updated approval of PD-L1 IHC 22C3 pharmDx means that the assay can be used to identify previously untreated patients with metastatic NSCLC expressing high levels of PD-L1 for treatment with KEYTRUDA. Prior to this, chemotherapy was the standard first-line treatment for most NSCLC patients. The labeling update also means that more patients in the second-line or later treatment setting — including patients with levels of PD-L1 expression of 1 percent or more — can also be identified for treatment with KEYTRUDA.

"This expanded intended use for our FDA-approved PD-L1 IHC 22C3 pharmDx assay is a step towards providing first-line metastatic NSCLC patients with immunotherapy as an option. PD-L1 IHC 22C3 pharmDx allows pathologists to confidently determine, and report PD-L1 expression status for a patient’s tumor. This critical diagnostic information informs oncologists’ treatment decisions around KEYTRUDA," said Jacob Thaysen, president of Agilent’s Diagnostics and Genomics Group. "Pathologists recognize the need for approved and validated tests, and our companion diagnostic gives them a highly accurate tool to inform oncologists on PD-L1 expression."

"PD-L1 is an important biomarker for use in identifying those patients with metastatic non-small cell lung cancer who are most likely to benefit from treatment with KEYTRUDA," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "With the approval of both the medicine and companion diagnostic to include first-line evaluation and treatment, and the broadening of the Dako PD-L1 IHC 22C3 pharmDx label in the second-line and later treatment setting, we now have the opportunity to help many more patients with this devastating disease."

Lung cancer is the leading cause of cancer-related death worldwide, and NSCLC accounts for 80 percent of all lung cancers.

PD-L1 IHC 22C3 pharmDx was developed in partnership with Merck & Co., Inc. (known as MSD outside the U.S. and Canada), maker of the anti-PD-1 therapy, KEYTRUDA.

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.