On October 2, 2017 SELLAS Life Sciences Group, Ltd. (SELLAS), a development-stage biopharmaceutical company focused on novel cancer immunotherapies for a broad range of cancer indications, reported entry into a Clinical Trial Collaboration and Supply Agreement for the conduct of a combination clinical trial targeting multiple cancer types with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada) (Press release, Galena Biopharma, OCT 2, 2017, View Source [SID1234520742]). SELLAS’ Wilms tumor-1 (WT1)-targeting peptide immunotherapeutic agent, galinpepimut-S, will be administered in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase 1/2 trial enrolling patients in five cancer indications, including both hematologic malignancies and solid tumors.

The purpose of the trials is to determine if the administration of galinpepimut-S in combination with KEYTRUDA has the potential to demonstrate clinical activity in the presence of macroscopic disease, where monotherapy with either agent would have a more limited effect. The rationale for the study is based upon the presumed immunobiologic and pharmacodynamic synergy between the two agents, whereby the negative influence of tumor microenvironment factors on the immune response is mitigated by PD-1 inhibition (by KEYTRUDA) thus allowing the patients’ own immune cells to invade and destroy cancerous growth deposits specifically sensitized against WT1 (by galinpepimut-S).

Angelos Stergiou, MD, ScD h.c., Vice Chairman and Chief Executive Officer of SELLAS, stated, “SELLAS is enthused to embark upon this trial with MSD as we look to expand the utility of galinpepimut-S in combination with other agents. The KEYTRUDA/galinpepimut-S active immunotherapy combination is positioned to exploit the unique features of each of these two agents through potential synergistic immune-based mechanisms of antitumor action. If positive, this clinical effort will allow us to evaluate indications whereby galinpepimut-S and KEYTRUDA could be further studied in combination, providing the basis for a potentially promising cancer immunotherapy approach in the future.”

The Phase 1/2 trial will utilize a combination of galinpepimut-S plus KEYTRUDA in patients with WT1-positive relapsed or refractory tumors. Specifically, the study is expected to explore the following cancer indications: colorectal (arm enriched in but not exclusive to patients with microsatellite instability-low [MSI-L]), ovarian, small cell lung, triple-negative breast, and AML. This study will assess the efficacy and safety of the combination, comparing overall response rates (ORRs) and immune response markers achieved with the combination versus prespecified rates based on those seen with KEYTRUDA alone in comparable patient populations. The trial is anticipated to begin in the first half of 2018.

Galinpepimut-S is currently expected to enter a pivotal, Phase 3 clinical trial in patients with acute myeloid leukemia (AML) and is also in various development phases in multiple myeloma (MM) and ovarian cancer, while additional indications are expected as a monotherapy or in combination with other immuno-oncology agents. Galinpepimut-S demonstrated positive Phase 2 clinical results as well as induction of strong and sustained immune responses (both CD4+ and CD8+) against the WT1 antigen in AML and malignant pleural mesothelioma in 2016 and MM in 2017, while being able to access a broad range of human leukocyte antigen (HLA) types; tolerability has been good across indications to date.

The Clinical Trial and Collaboration Supply Agreement is between Sellas Life Sciences Group Ltd. and MSD through a subsidiary. Additional details of the collaboration were not disclosed.

On October 2, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported that it received approval from the New York State (NYS) Clinical Laboratory Evaluation Program (CLEP) for its FoundationACT blood-based circulating tumor DNA (ctDNA) assay (Press release, Foundation Medicine, OCT 2, 2017, View Source [SID1234520741]). The CLEP regulates and seeks to ensure the accuracy and reliability of test results in clinical laboratories located in or accepting specimens from NYS. With the approval of FoundationACT, the company’s suite of comprehensive genomic profiling products is available to oncologists and patients in all 50 states.

The FoundationACT assay is designed to identify clinically-relevant genomic alterations driving the growth of a patient’s cancer. This liquid biopsy assay can help physicians identify treatment options by providing clinically actionable information about potential targeted therapies and/or available clinical trials from only a blood sample. FoundationACT is analytically validated to detect genomic alterations in more than 60 of the most clinically-relevant cancer genes in solid tumors.

“We believe New York state conducts one of the most rigorous assessments of laboratory developed tests in the nation, and its approval of FoundationACT speaks to the quality and reliability of our assay,” stated Jeffrey S. Ross, M.D., medical director for Foundation Medicine. “We’re delighted to begin offering FoundationACT to physicians and their patients in the State of New York, and most importantly, to advance access and improve treatment options for individuals living with cancer.”

On October 02, 2017 Endocyte, Inc. (NASDAQ Global Market:ECYT), a biopharmaceutical company developing targeted therapeutics for personalized cancer treatment, reported the completion of an exclusive worldwide license of PSMA-617 from ABX GmbH. Endocyte intends to move quickly into Phase 3 development of 177Lu-PSMA-617, a radioligand therapeutic (RLT) that targets the prostate-specific membrane antigen (PSMA), present in approximately 80% of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Endocyte, OCT 2, 2017, View Source [SID1234520740]).

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177Lu-PSMA-617 delivers the short-range beta-emitting radioactive isotope lutetium (177Lu) selectively to tumor cells while by-passing non-PSMA-expressing healthy cells with encouraging efficacy and safety results. As highlighted in roughly 20 peer reviewed publications of studies in the post-chemotherapy compassionate use setting, 177 Lu-PSMA-617 has consistently demonstrated a PSA response (defined as greater than 50% decline from baseline) in 40% to 60% of patients, and a RECIST response rate in soft tissue disease of between 40% and 50%.

“This transaction is transformational to Endocyte, accelerating our path to commercialization. 177Lu-PSMA-617 has the potential to be the first-in-class RLT to address both bone and soft tissue disease, and it is profoundly important to the many patients suffering from mCRPC,” said Mike Sherman, president and CEO of Endocyte. “Our experience with PSMA targeting and companion imaging development, in addition to our relationships with distinguished prostate cancer investigators from around the world, uniquely position Endocyte to lead this therapy to registration. We intend to seek regulatory approval to initiate a Phase 3 registration trial of 177Lu-PSMA-617 in early 2018. By focusing the company’s resources on the execution of this program, we project trial completion as early as 2020.”

Mr. Sherman continued, “Endocyte remains strongly committed to careful expense management and maintaining a strong balance sheet. With the exception of a very targeted effort to generate proof-of-concept data for our CAR T-cell program, we will focus our resources on the development of 177Lu-PSMA-617. We will explore out-licensing opportunities for all other development programs.”

“Despite advances in the last decade that slow the progression of prostate cancer, once metastasized it is nearly always lethal, leading to 300,000 worldwide deaths annually. 177Lu-PSMA-617 has demonstrated the most compelling activity of any drug currently in development for these post-chemotherapy patients,” said Alison Armour, chief medical officer.

PSMA-617 was developed at DKFZ (German Cancer Research Center) and University Hospital Heidelberg and exclusively licensed to ABX GmbH in Germany for early clinical development. As a result of the enthusiasm of physician investigators and patients, the investigational therapy has been evaluated in hundreds of patients through both compassionate use studies and prospective trials.

“The data generated thus far have created significant enthusiasm for 177Lu-PSMA-617. PSMA is a promising target in prostate cancer and radioligand therapy may be the best application for this target,” said Michael Morris, MD, associate professor, Genitourinary Oncology, Memorial Sloan Kettering Cancer Center. “Particularly where disease has become resistant to current therapies, there is a tremendous need for new approaches and I look forward to working with Endocyte to investigate this innovative, first-in-class therapy for prostate cancer patients.”

Clinical Data Presented at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper)

Dr. Michael Hofman of the Peter MacCallum Cancer Center in Melbourne, Australia presented the results of an open-label, single-arm, non-randomized pilot study of 177 Lu-PSMA-617 in September 2017, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. Thirty mCRPC patients were treated with up to four cycles of 4-8 GBq. Primary endpoints included safety and efficacy as defined by PSA response, quality of life, and imaging response.

The results showed a remarkable 57% PSA response rate ( > 50% reduction) and 71% interim response rate in soft tissue lesions (as measured by RECIST criteria) in patients who had previously failed such conventional therapies as docetaxel, cabazitaxel, enzalutamide and abiraterone. Median overall survival was 12.7 months. The drug was well-tolerated, with a low rate of adverse effects and no renal toxicity. Significantly improved quality of life scores and reduction in pain scores were recorded in 37% and 43% of patients, respectively. This trial has subsequently been expanded to 50 subjects from the original 30, with updated results expected to be presented in 2018.

On October 2, 2017 Atossa Genetics (NASDAQ:ATOS), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods for breast cancer and other breast conditions, reported a new program using Chimeric Antigen Receptor Therapy, or CAR-T (Press release, Atossa Genetics, OCT 2, 2017, View Source [SID1234520739]). Atossa plans to use its proprietary intraductal microcatheter technology to deliver CAR-T cells into the ducts of the breast for the potential targeted treatment of breast cancer.

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Atossa’s novel approach uses its proprietary intraductal microcatheter technology for the potential transpapillary, or “TRAP,” delivery of T-cells that have been genetically modified to attack breast cancer cells. Atossa believes this method has several potential advantages: reduced toxicity by limiting systemic exposure of the T-cells; improved efficacy by placing the T-cells in direct contact with the target ductal epithelial cells that are undergoing malignant transformation; and, lymphatic migration of the CAR-T cells along the same path taken by migrating cancer cells, potentially extending their cytotoxic actions into the regional lymph system, which could limit tumor cell dissemination. Atossa’s approach is in the research and development phase and has not been approved by the FDA or any other regulatory body. Pre-clinical studies, and clinical studies demonstrating safety and efficacy among other things, and regulatory approvals will be required before commercialization.

“We have been encouraged by the promise that CAR-T has shown in other forms of cancer, which is usually delivered systemically. We believe that our proprietary TRAP technology could provide a potentially safer yet effective method to deliver CAR-T,” stated Steven Quay, MD, PhD, Atossa CEO. “We believe that TRAP CAR-T, as we are calling this novel approach to adaptive T-cell therapy in breast cancer, will provide another approach to breast cancer, and that it may be particularly well-suited for the deadlier forms of breast cancer such as ‘triple negative.’ Now that we have developed a foundational intellectual property position with respect to TRAP CAR-T, we intend to continue research and development through partnership with leading investigators, institutions, and organizations around the world, bringing Atossa’s technology and expertise in TRAP delivery together with experts in cancer immunology and T-cell biology. Multiple studies in both animals and humans have shown that a number of therapeutics can be delivered by the TRAP, intraductal route,” Dr. Quay added.

About TRAP CAR-T

The transpapillary (TRAP) delivery of therapeutics in breast cancer clinical trials have demonstrated “that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity” (Zhang B, et al. Chin J Cancer Res. 2014 Oct;26(5):579-87; www.ncbi.nlm.nih.gov/pubmed/25400424).

T cells are removed from a patient and modified so that they express receptors specific to the patient’s particular breast cancer. The T cells, which can then recognize and kill the cancer cells, are reintroduced into the patient using a microcatheter into the natural ducts of the breast.

Chimeric antigen receptors (or, “CARs” and also known as chimeric immunoreceptors, chimeric T cell receptors, artificial T cell receptors or CAR-T) are engineered receptors, which graft an arbitrary specificity onto an immune effector cell (T cell). Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T cell, with transfer of their coding sequence facilitated by retroviral vectors. The receptors are called chimeric because they are composed of parts from different sources.

CAR-T technology has been the subject of much attention recently as pioneer CAR-T company Kite Pharma recently announced its acquisition by Gilead, and the FDA has recently approved Novartis’s Kymriah for treatment of B-cell Acute Lymphoblastic Leukemia.