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 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 Genprex, Inc. (NASDAQ: GNPX), a clinical stage gene therapy company, reported an update on development of its lead drug candidate, Oncoprex immunogene therapy, in combination with immunotherapy for the treatment of non-small cell lung cancer (NSCLC) (Press release, Genprex, JUL 1, 2019, View Source [SID1234537346]).

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In July 2018, the company entered a Sponsored Research Agreement with The University of Texas MD Anderson Cancer Center ("MD Anderson") to fund a research study entitled, "A Novel Therapeutic Approach for the Treatment of Cancer Using a Combination of the Multifactorial Tumor Suppressor Gene TUSC2 and Immunotherapy." The TUSC2 gene is the active agent in Genprex’s Oncoprex immunogene therapy. The study was budgeted to cost $2.03 million.

The study aimed to develop a novel therapeutic approach for the treatment of cancer using a combination of the tumor suppressor gene TUSC2 and immunotherapy, including immune checkpoint inhibitors and anti-PD1 and/or anti-CTLA-4 antibodies. A specific objective of the study was to validate therapeutic efficacy of the TUSC2 and immune checkpoint blockade combination in humanized cancer mouse models. This milestone was completed with positive results presented in a poster by Genprex’s collaborators from MD Anderson at the American Association of Cancer Research Meeting in April 2019, which is available on the company’s website.

Research under the Sponsored Research Agreement is continuing. Further aims of the research include evaluating TUSC2 in combination with immunostimulatory adjuvants and targeted small molecule drugs. Additional goals of the study also include identification of biomarkers that predict response to TUSC2-immunotherapy combinations

Based on data from this study and data from prior clinical and pre-clinical studies, Genprex is working with its Scientific Advisory Board and outside consultants to design a clinical trial for the study of Oncoprex in combination with a checkpoint inhibitor for treatment of non-small cell lung cancer, with the goal of being in a position to enroll patients in the first quarter of 2020.

"Recent studies have shown that less than half of cancer patients qualify for approved immunotherapies based on the patient’s PD-1 or PD-L1 protein expression level," said Julien Pham, President and Chief Operating Officer of Genprex. "Current immunotherapy treatment is only benefitting a small number of cancer patients. We are working to fill this gap by combining our lead drug candidate with approved immunotherapies to give patients more treatment options. The preclinical studies have shown encouraging data that this combination could be a viable treatment option for late-stage non-small cell lung cancer."

On July 1, 2019 Synergys Biotherapeutics, a preclinical stage biotherapeutics company developing Vasculogenic Mimicry (VM)-blocking antibody fusion drugs for cancer treatment reported the granting of its second Phase 1 Small Business Innovation Research (SBIR) award by the National Cancer Institute (NCI) (Press release, Synergys Biotherapeutics, JUL 1, 2019, View Source [SID1234537345]). This award will support the development for ovarian cancer an anti-HER2 antibody fusion candidate that contains a highly anti-angiogenic dimeric mutant endostatin as its fusion partner. The uniqueness of the fusion is its ability to inhibit both vasculogenic mimicry, which is the direct formation of vascular channels by tumor cells, as well as angiogenesis, i.e. the development of new vasculature by endothelial cells. Synergys was awarded its first SBIR grant for the development of an anti-EGFR-endostatin mutant fusion that is currently being developed for the treatment of Triple Negative Breast Cancer (TNBC).

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The fusion candidates were derived from A-TAP (Antibody-Targeted Anti-vascularization Payload) system that was pioneered by Drs. Joseph Rosenblatt, M.D., Professor and Chief of the Hematology Division and Seung-Uon Shin, Ph.D., Research Associate Professor, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL. Synergys has established a long-term collaboration with Drs. Rosenblatt and Shin in developing the fusion candidates and exploring the molecular mechanism of VM inhibition in decreasing tumor burden and metastasis inhibition in cancer.

Regarding the award, Dr. Rosenblatt notes, "As a co-PI of the project, I am excited to note that our pioneering work on vasculogenic mimicry inhibition in cancer is being recognized by the SBIR review boards for its therapeutic potential, first for TNBC and now again for ovarian cancer. We look forward to continuing our collaboration with Synergys for the development of the antibody fusion molecules as new targeted therapeutics for various cancers."

Dr. Rathin Das, PhD, CEO of Synergys said, "Receiving our second SBIR award from the NCI is both validation and endorsement of the VM-blocking A-TAP platform thereby providing significant impetus for utilizing it for the development of breakthrough treatment modalities for a variety of solid cancers."

On July 1, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for neratinib in combination with capecitabine for the treatment of patients with HER2-positive metastatic breast cancer who have failed two or more prior lines of HER2-directed treatments (third-line disease) (Press release, Puma Biotechnology, JUL 1, 2019, View Source [SID1234537344]).

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Neratinib was originally approved by the U.S. Food and Drug Administration in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX tablets. In September 2018 NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and are less than one year from completion of prior adjuvant trastuzumab-based therapy.

The sNDA is supported by the results of the Phase III NALA trial, a randomized controlled trial of neratinib plus capecitabine versus Tykerb (lapatinib) plus capecitabine in patients with third-line HER2-positive metastatic breast cancer.

For the primary analysis of centrally confirmed PFS, treatment with neratinib plus capecitabine resulted in a statistically significant improvement in centrally confirmed PFS (hazard ratio=0.76, p=0.0059) compared to treatment with lapatinib plus capecitabine. Because the proportional hazard assumption did not hold, the statistical analysis plan for the NALA trial prespecified that a restricted means survival analysis at 24 months would be performed. In this prespecified analysis the mean PFS for the patients treated with neratinib plus capecitabine was 8.8 months and the mean PFS for the patients treated with lapatinib plus capecitabine was 6.6 months.

For the primary analyses of OS, neratinib plus capecitabine resulted in an improvement in OS that trended positively in favor of the neratinib plus capecitabine arm of the study (hazard ratio = 0.88, p=0.21). The median OS for the patients treated with neratinib plus capecitabine was 21.0 months and the median OS for the patients treated with lapatinib plus capecitabine was 18.7 months. In the prespecified restricted means analysis the mean OS at 48 months for the patients treated with neratinib plus capecitabine was 24.0 months and the mean OS for the patients treated with lapatinib plus capecitabine was 22.2 months.

For the secondary endpoint of time to intervention for symptomatic central nervous system disease (also referred to as brain metastases), the results of the trial showed that treatment with neratinib plus capecitabine led to an improvement over the combination of lapatinib plus capecitabine. The overall cumulative incidence for intervention for CNS metastases at 54 months was 22.8% of patients for the neratinib plus capecitabine arm and 29.2% of patients for the lapatinib plus capecitabine arm (p=0.043, descriptive). For the secondary endpoint of duration of response, neratinib plus capecitabine treatment resulted in a longer duration of response compared to lapatinib and capecitabine treatment, with a median response of 8.54 months compared to a median response of 5.55 months (HR = 0.495, p = 0.0004, descriptive).

Treatment-emergent adverse events (TEAEs) were similar between arms: TEAEs leading to neratinib/lapatinib discontinuation were lower with neratinib (10.9%) than with lapatinib (14.5%). There was a higher rate of grade 3 diarrhea with neratinib plus capecitabine compared to lapatinib plus capecitabine (24.4% vs 12.5%); however, the discontinuations due to diarrhea (neratinib plus capecitabine: 2.6%, lapatinib plus capecitabine: 2.3%) were similar in both arms.

"We are very pleased to announce this important regulatory milestone," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "Although the use of HER2 directed agents in the metastatic setting has positively impacted the treatment of the disease in the first and second line settings, patients with HER2 positive metastatic breast cancer who have progressed on two or more prior treatments continue to need additional treatment options. We look forward to working with the FDA during its review of this submission."

About NALA

The NALA trial is a randomized controlled Phase III trial of neratinib plus capecitabine versus Tykerb (lapatinib) plus capecitabine in patients with third-line HER2-positive metastatic breast cancer. The trial enrolled 621 patients who were randomized (1:1) to receive either neratinib plus capecitabine or lapatinib plus capecitabine. The trial was conducted globally at sites in North America, Europe, Asia-Pacific and South America. The co-primary endpoints of the trial are centrally confirmed progression free survival (PFS) and overall survival (OS). An alpha level of 1% was allocated to the PFS and 4% allocated to OS. The study was to be considered positive if either of the co-primary endpoints was positive. Puma reached agreement with the FDA under a Special Protocol Assessment (SPA) for the design of the Phase III clinical trial and the European Medicines Agency (EMA) also provided follow-on scientific advice (SA) consistent with that of the FDA regarding the Company’s Phase III trial design and endpoints used in the trial.