On July 1, 2019 Amphivena Therapeutics highlighted initial data from the dose-escalation portion of the First-in-Human Phase 1 trial evaluating AMV564 in patients with relapsed or refractory acute myeloid leukemia (AML, AMV564-101, NCT03144245) in an oral presentation June 15 at the 24th European Hematology Association (EHA) (Free EHA Whitepaper) meeting in Amsterdam (Abstract S877) (Press release, Amphivena Therapeutics, JUL 1, 2019, View Source [SID1234537347]). The oral presentation of data from 33 patients treated within 9 cohorts demonstrated that AMV564 is active in relapsed or refractory AML and expanded upon the data from 26 patients presented at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2018. AMV564 is a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3 resulting in T cell directed lysis of leukemic blasts and myeloid-derived suppressor cells (MDSCs) without affecting monocytes and neutrophils.

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Gail Roboz, M.D., Professor of Medicine, Director of the Leukemia Program, and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center and a Principal Investigator for the study, presented on behalf of the study team. "While this is a Phase 1 study," she said, "we believe that AMV564 has demonstrated promising monotherapy activity, including a CR, CRi and PR and evidence of durability in a high risk, older patient population on a 14-day dosing regimen. The data show that AMV564 is well-tolerated with no dose limiting toxicities through 250 mcg and only Grade 1 and Grade 2 cytokine release syndrome distinguishing the safety of AMV564 from other drugs in development for myeloid malignancies."

"AMV564 has demonstrated novel clinical activity for a T cell engager by rapidly and selectively eliminating leukemic blasts and rare immature, granulocytic and monocytic MDSCs while sparing normal CD33-expressing cells, including neutrophils and monocytes. High levels of circulating MDSCs are associated with poor prognosis for cancer patients. Our drug’s ability to selectively eliminate MDSCs rather than modulating MDSC pathways provides a unique opportunity to evaluate the role of these immune suppressive cells in cancer," said Jeanmarie Guenot, Ph.D., Amphivena Chief Executive Officer and President.

Dr. Roboz has served as a consultant for Amphivena, Celgene, Bayer, Otsuka, Pfizer, Astellas Pharmaceuticals, Argenx, Astex Pharmaceuticals, Hoffman-La Roche, Janssen, Novartis, AbbVie, Sandoz, Eisai, Jazz Pharmaceuticals, Celltrion, Orsenix and Daiichi Sankyo.

About AMV564-101

AMV564-101 is a First-in-Human dose escalation and dose expansion Phase 1 trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMV564 in patients with relapsed or refractory AML after 1-2 prior induction regimens (with a standard anthracycline-based regimen or hypomethylating agent) and no more than 2 prior salvage regimens. The Phase 1 study is currently open at Washington University School of Medicine, MD Anderson Cancer Center, NewYork-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, Fred Hutchinson Cancer Research Center, The Ohio State University Wexner Medical Center, University of Pennsylvania Medical Center, Northwestern Memorial Hospital, and The Johns Hopkins Hospital.

On July 1, 2019 Foundation Medicine, Inc. reported it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for LYNPARZA (Olaparib) for first line maintenance therapy in BRCA-mutated advanced ovarian cancer (Press release, Foundation Medicine, JUL 1, 2019, View Source [SID1234537348]). FoundationOne CDx is an FDA-approved comprehensive genomic profiling (CGP) test for all solid tumors that incorporates multiple companion diagnostics. FoundationOne CDx detects tumor BRCA1 and BRCA2 mutations including both germline (inherited) and somatic (acquired) mutations.i FoundationOne CDx may help identify more women who could benefit from Lynparza as compared to conventional testing methods that only identify germline BRCA mutations. Germline-only BRCA1/2 testing identifies approximately half of all BRCA1/2 mutations.ii,iii

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"Foundation Medicine is proud to receive FDA approval for another important companion diagnostic on FoundationOne CDx, our broad companion diagnostic test that is clinically and analytically validated for all solid tumors," stated Brian Alexander, M.D., M.P.H. Foundation Medicine’s Chief Medical Officer. "It is imperative that women with advanced ovarian cancer receive rigorous testing for BRCA1/2 mutations such as FoundationOne CDx, which includes both germline and somatic mutations, to determine if they are a candidate for PARP inhibitors."

In December of 2018, AstraZeneca (LSE/STO/NYSE: AZN) and Merck & Co., Inc. announced that the FDA approved Lynparza for use as maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to 1st-line platinum-based chemotherapy.

Foundation Medicine, AstraZeneca and Merck have an ongoing collaboration to support the development of companion diagnostics for Lynparza in prostate cancer.

About FoundationOne CDx
FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. FoundationOne CDx is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source

On June 30, 2019 LSK BioPharma (or "LSKB"), a US-based biopharmaceutical firm and Jiangsu Hengrui Medicine, Co., Ltd. (SHA:600276, or "Hengrui"), one of the largest and most innovative fully-integrated biopharmaceutical companies based in China, reported the first patient has been enrolled in a pivotal global phase 3 clinical study of PD-1 antibody camrelizumab (SHR-1210) plus rivoceranib (commonly known as apatinib) versus sorafenib as a first-line therapy in subjects with advanced hepatocellular carcinoma (HCC) (Press release, LSK BioPharma, JUN 30, 2019, View Source [SID1234537337]). Rivoceranib, a selective VEGFR-2 inhibitor commonly known as apatinib, was approved in 3rd line gastric cancer in China in December 2014. Camrelizumab is a humanized anti-PD-1 monoclonal antibody which recently received the approval in China for classic Hodgkin’s Lymphoma (cHL).

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"We are excited to study the potential synergies of rivoceranib with immunotherapy and demonstrate the benefits to HCC patients in a first line setting," said Dr. Steve Norton, Vice President of Drug Development at LSKB.

Hengrui has been conducting an open-label, single arm multicenter phase 2 study (NCT03463876) to evaluate the efficacy and safety of the combination of camrelizumab and apatinib in patients with advanced HCC in China, where Hengrui has received approval of apatinib monotherapy for advanced gastric cancer. At ASCO (Free ASCO Whitepaper) 2018, it was reported that the objective response rate (ORR) and disease control rate (DCR) were 50.0% and 85.7%, respectively, among 14 evaluated advanced HCC patients treated by camrelizumab in combination with apatinib in an open-label, phase 1 study in China (Xu et al., NCT02942329). In addition, camrelizumab and apatinib combination therapy is also being evaluated by Hengrui for multiple indications including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC) in China.

Based upon earlier studies, it is hypothesized that the combination of rivoceranib and camrelizumab may enhance the immune system, aiding the fight against cancer. In addition to the known anti-angiogenic effects of rivoceranib, it may also enhance camrelizumab’s anti-tumor activity by normalizing tumor vasculature and reversing the tumor suppressive immune microenvironment.

About Rivoceranib (Apatinib)

Rivoceranib, also known as apatinib or Aitan (brand name) in China, is the first successful small-molecule angiogenesis inhibitor in gastric cancer. Rivoceranib is investigational outside of China including in the United States; and safety and efficacy have not been established. It acts by inhibiting angiogenesis, a critical process in cancer growth and proliferation. Specifically, rivoceranib selectively inhibits VEGFR-2 which mediates the primary pathway for tumor-mediated angiogenesis.

Hengrui, who owns the China rights to rivoceranib, received the approval from China National Medical Products Administration (NMPA, formerly known as CFDA) in 2014 to market the drug under the brand name Aitan in China for advanced gastric cancer. LSKB, which holds the global rights (ex-China), has completed enrollment of a global (12 countries including US, Japan, Korea, Italy, Germany, and Russia) phase 3 clinical trial of rivoceranib in advanced or metastatic gastric cancer patients. Rivoceranib (apatinib) is currently listed in 264 clinical studies on www.clinicaltrials.gov with over 20,000 patients enrolled or planned to be enrolled in trials targeting numerous cancers including GC, colorectal cancer (CRC), HCC, NSCLC, esophageal cancer, thyroid cancer, mesothelioma, and neuroendocrine tumors. It has also shown potential to improve outcomes in combination with chemotherapeutics and immunotherapy, as well as for maintenance therapy. LSKB has received notification designating rivoceranib as an orphan medicinal product for the treatment of gastric cancer from the European Commission in the European Union, the US FDA, as well as the MFDS in South Korea.

Rivoceranib was developed by Advenchen Laboratories in Southern California under the designation YN968D1. The compound was exclusively licensed to Hengrui in China (2005) and LSKB (2007) for rest of the world.

About Camrelizumab (SHR-1210)

Camrelizumab (SHR-1210) is an investigational humanized monoclonal antibody recognizing the programmed death-1 (PD-1) receptor. Camrelizumab functions as an immune checkpoint inhibitor by specifically blocking the interaction between PD-1 and PD-L1 and reversing the immunosuppressive signal of PD-1 on the T cell. Approximately 72 clinical studies on camrelizumab in multiple indications including lung cancer, liver cancer, gastric cancer, esophageal cancer, nasopharyngeal carcinoma, lymphoma, melanoma and other advanced solid tumors are being conducted in China and Australia as monotherapy or in combination with other therapeutic agents. A marketing application for camrelizumab for relapsed/refractory classic Hodgkin’s Lymphoma was submitted by Hengrui to China NMPA, which was accepted in April 2018, and is currently under review.

On June 28, 2019 Menarini Ricerche reported the publication of the results of a non-clinical study describing the characterization of the anti-CD205 Antibody-Drug Conjugate (ADC) MEN1309/OBT076. These findings have been published by the journal Molecular Cancer Therapeutics (View Source) (Press release, Menarini, JUN 28, 2019, View Source [SID1234537332]).

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The study showed that CD205, a transmembrane glycoprotein, is robustly expressed in a variety of solid malignancies, such as pancreatic and bladder tumors, as well as triple negative breast cancer (TNBC). In these settings, MEN1309/OBT076 showed substantial in vitro antitumor activity. These results were confirmed in vivo where MEN1309/OBT076 demonstrated potent antitumor activity in TNBC, pancreatic, and bladder xenografts and patient-derived PDX models, resulting in durable responses and complete tumor regressions.

"These non-clinical data show the promising activity of MEN1309/OBT076 in solid tumors expressing CD205, thus supporting the clinical development of MEN1309, which is being evaluated in the phase I SHUTTLE study" (NCT03403725), said Monica Binaschi, PhD, Director of the Preclinical and Translational Sciences Department of Menarini Ricerche. "Moreover, these results provide a strong rationale for one of the key elements of the clinical development strategy of MEN1309/OBT076, represented by the specific targeting of patients with tumors expressing CD205 as confirmed by an appropriate assay developed in-house. The published study represents an example of fruitful scientific collaboration between academic centers of excellence in oncology research and industry, involving Joaquin Arribas and his team at the Vall D’Hebron Institute of Oncology (VHIO) in Barcelona, as well as our partner Oxford BioTherapeutics (OBT)."

About MEN1309/OBT076

MEN1309/OBT076, is an ADC comprising a fully human antibody targeting CD205, coupled to the DM4 toxin. MEN1309/OBT076 is in development for a number of CD205-driven tumors.

MEN1309/OBT076 is currently in development with a multicenter first-in-human clinical study in major European oncology centers in Italy, Spain, Belgium and UK, (NCT03403725) to evaluate the activity of the antibody in the treatment of metastatic solid cancers, including gastric cancer, triple-negative breast cancer, bladder cancer and pancreatic cancers as well as non-Hodgkin lymphoma (NHL). This clinical trial follows a precision oncology approach, key component of Menarini’s strategy, recruiting only patients positive for the expression of the therapeutic target CD205. Dose-Escalation phase I clinical trial is starting in the United States in highly experienced academic centers under the sponsorship of OBT.

On June 28, 2019 Athenex, Inc. (Nasdaq: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer, reported that the Company has strategically expanded its presence in Europe and Latin America to grow its global clinical research and development capacity (Press release, Athenex, JUN 28, 2019, View Source [SID1234573890]). The Company believes these initiatives have the potential to enhance Athenex’s capacity to conduct global clinical studies and support its regional marketing decision process. They are part of the Company’s strategy to build on its current strong presence in U.S. and Asia, and help maximize the global potential of its pipeline.

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Athenex’s oncology-focused pipeline currently has nine clinical candidates, including two drug candidates in Phase III development. In line with the Company’s goal to expand its capability and bandwidth to optimize global development and commercialization of its pipeline products, Athenex has been evaluating operational opportunities in Europe and Latin America.

As part of Athenex’s strategy to establish operations in Europe, the second largest healthcare market in the world, the Company has formed a subsidiary in the United Kingdom and established offices in Manchester. The Company is currently conducting clinical studies in the United Kingdom and intends to continue expanding its research and development capabilities in the region.

In Latin America, Athenex recently entered into a definitive agreement to acquire certain assets of CIDAL Limited in exchange for shares of Athenex common stock, subject to customary closing conditions. CIDAL is a contract research organization with headquarters in Guatemala and operations in various countries in Latin America. CIDAL has provided important CRO services and support to Athenex, including for its Phase III study of oral paclitaxel and encequidar for metastatic breast cancer. The asset purchase is expected to strengthen Athenex’s clinical research and operations capabilities and support the Company’s clinical development worldwide.

"These initiatives represent an important step in our ongoing strategic efforts to expand our clinical research and operations for global development, with the potential for increased clinical research efficiencies and cost-effectiveness" said Dr. Johnson Lau, Chairman and Chief Executive Officer of Athenex. "Our office in Manchester will enable us to evaluate the best strategy for Europe, an important market for Athenex. We have been engaging with many experienced pharma/biotech specialists who are already contributing to our research programs and look forward to working more closely with these talents. We are also delighted to extend our operations in Latin America through CIDAL, which we believe will increase our bandwidth for clinical research and regulatory development. We believe having a stronger presence in these territories will position us well to evaluate new R&D and commercialization opportunities in Europe and Latin America."