This $567,059 Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) supports research at the University of Texas MD Anderson Cancer Center to investigate the use of the CDK4/6 inhibitor abemaciclib, alone or in combination with circular RNA (circRNA) silencing, to enhance anti-tumor immune responses in soft-tissue sarcomas. The research aims to elucidate the interplay between abemaciclib, circRNAs, and immune responses in sarcoma, with a focus on how...
This $253,273 Project Grant, awarded by the National Cancer Institute (NCI) under the Cancer Research Manpower (CFDA 93.398) program, will fund research to validate circulating tumor DNA (ctDNA) as a clinically informative biomarker for adolescent and young adult (AYA) patients with sarcomas. The primary objectives are to: 1) Determine ctDNA-based prognostic thresholds for risk of relapse in fusion-negative sarcomas at baseline; 2) Determine ctDNA-based prognostic thresholds for risk of...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $994,859 to Cytoagents Inc. to develop the compound CTO1681 for preventing and treating cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T-cell therapy. CRS is a serious and potentially life-threatening adverse event that can occur with CAR T-cell treatments for hematologic malignancies. The funding will support a Phase 1b clinical trial to assess the...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), provides $1,427,270.00 to Syntrix Biosystems Inc. to conduct a dose expansion study of SX-682 alone and in combination with decitabine in patients with myelodysplastic syndromes (MDS). MDS is a pre-leukemic syndrome to acute myeloid leukemia (AML), and current treatment options have suboptimal response rates and limited durability. The study aims to advance the...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $593,028 to the Beckman Research Institute of the City of Hope to conduct research on the role of IL-6/STAT3 signaling in CIC-DUX4 fusion sarcoma metastasis and immunosuppression. The research aims to determine if targeting IL-6/STAT3 signaling can effectively block CIC-DUX4 fusion oncoprotein-driven tumor growth, metastasis, and immunosuppression in this aggressive and understudied...
This $400,000 Project Grant awarded by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) supports the development and testing of a novel nanoparticle formulation of the mediator kinase inhibitor SNX631-6 for the treatment of peritoneal ovarian cancer metastases. The goal is to optimize the nanoparticle delivery system to improve the pharmacokinetics and efficacy of this targeted cancer therapy when administered intraperitoneally, compared to oral administration. The...
This $514,405 Project Grant awarded by the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) supports research conducted by Sanford Research, a non-profit biomedical research organization, to investigate the mechanisms underlying the role of cancer-dependent skeletal pathways in the development and progression of osteosarcoma. The research aims to: 1) Elucidate the role of cancer-dependent skeletal genes and pathways in osteoblast-specific p53 and Rb loss-of-function models,...
This $546,625 federal Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) aims to develop a new immunochemotherapy approach for the treatment of metastatic colorectal cancer (mCRC). The key products and services to be delivered under this 5-year award include: Developing and characterizing a novel nanoparticle carrier system that can co-deliver small interfering RNA (siRNA) targeting the IRHOM1 protein and a chemotherapeutic agent...
This $800,000 Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) aims to develop a longer-acting version of the novel anti-cancer biologic drug L-asparaginase (EBD-300). The goal is to expand the use of this enzyme therapy beyond its current application in pediatric acute lymphoblastic leukemia (ALL) to also treat adult ALL patients and other cancer types. The awarded work will engineer and evaluate EBD-300 variants with improved in vivo persistence,...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $402,600.00 to the Sloan-Kettering Institute for Cancer Research to develop novel chimeric antigen receptor (CAR) T-cell therapies targeting the U5 snRNP200 protein for the treatment of acute myeloid leukemia (AML). The key objectives are to: Test the efficacy and safety of the U5 snRNP200-targeted CAR T-cells, including engineered versions that secrete IL-18, in preclinical AML models....
ASSESSING THE SAFETY AND EFFICACY OF SQ3370 IN A PHASE 1B DOSE-EXPANSION COHORT AT THE RECOMMENDED PHASE 2 DOSE IN PATIENTS WITH ADVANCED SARCOMA - ABSTRACT IN 2018, THE GLOBAL INCIDENCE OF NEW CANCER DIAGNOSES WAS ESTIMATED AT OVER 18 MILLION CASES, AND CANCER- RELATED DEATHS WERE ESTIMATED AT OVER 9.6 MILLION. OF THESE CASES, THE VAST MAJORITY WERE SOLID TUMORS, ACCOUNTING FOR MORE THAN 16 MILLION NEW CASES AND 8 MILLION CANCER DEATHS. THIS INCLUDES SOFT TISSUE SARCOMA (STS), A HETEROGENEOUS GROUP OF AGGRESSIVE MALIGNANT TUMORS THAT HAVE A POOR 5-YEAR SURVIVAL RATE OF ONLY 65%. IN THE U.S., AN ESTIMATED 13,000 PEOPLE WILL BE DIAGNOSED WITH STS IN 2020, AND MORE THAN 5,000 WILL DIE OF THE DISEASE. FOR PATIENTS DIAGNOSED WITH STS, TREATMENT OFTEN INVOLVES CHEMOTHERAPY WITH A CYTOTOXIC AGENT SUCH AS DOXORUBICIN (DOX), AN ANTHRACYCLINE THAT HAS BEEN USED TO INDUCE TUMOR REGRESSION IN A VARIETY OF NEOPLASTIC CONDITIONS. DOX IS ALSO KNOWN TO INDUCE IMMUNOGENIC CELL DEATH AND ENHANCE TUMOR RESPONSIVENESS TO IMMUNE CHECKPOINT BLOCKADE THERAPIES. UNFORTUNATELY, THE EXTENDED USE OF DOX IN PATIENTS IS LIMITED BY SEVERE TOXIC SIDE EFFECTS-MOST NOTABLY IRREVERSIBLE CARDIOTOXICITY AND BONE MARROW SUPPRESSION- WHICH CAN BE LIFE THREATENING. THEREFORE, THERE IS AN IMMEDIATE NEED FOR NEW METHODS TO REDUCE THE SYSTEMIC TOXICITY AND OFF-TARGET EFFECTS OF DOX WHILE MAINTAINING ITS ANTITUMOR EFFICACY SHASQI HAS DEVELOPED SQ3370, A NOVEL DRUG PRODUCT THAT WILL IMPROVE THE TREATMENT OF PATIENTS WITH INJECTABLE SOLID TUMORS UNDERGOING DOXORUBICIN (DOX)-BASED CHEMOTHERAPY. PRECLINICAL STUDIES DONE TO-DATE HAVE SHOWN THAT SQ3370 RESULTS IN SIGNIFICANT INHIBITION OF TUMOR GROWTH (BOTH INJECTED AND NON-INJECTED TUMORS), IMMUNE ACTIVATION, PROLONGED SURVIVAL, AND PROTECTION AGAINST TUMOR RECHALLENGE, WHILE EXHIBITING REDUCED SYSTEMIC SIDE EFFECTS COMPARED TO CONVENTIONAL DOX. EXTENSIVE PRECLINICAL DATA WITH SQ3370 HAS LED TO AN OPEN INVESTIGATIONAL NEW DRUG (IND) APPLICATION WITH THE U.S. FOOD AND DRUG ADMINISTRATION (FDA). A PHASE 1, FIRST- IN-HUMAN, DOSE-ESCALATION STUDY IS CURRENTLY ENROLLING TO EVALUATE THE SAFETY/TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF SQ3370 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS. THIS DIRECT TO PHASE II APPLICATION SEEKS TO EXPAND THIS TRIAL ONCE THE RECOMMENDED PHASE 2 DOSE (RP2D) HAS BEEN REACHED BY ADDING A DOSE EXPANSION COHORT OF 30 PATIENTS WITH SOFT-TISSUE SARCOMA USING A SIMON TWO-STAGE DESIGN. THE AIMS OF THIS PROJECT ARE TO ASSESS 1) SAFETY/TOLERABILITY AND 2) EFFICACY OF SQ3370 IN THIS COHORT TO DETERMINE IF THE STUDY SHOULD PROCEED TO A PHASE 2 CLINICAL TRIAL. THESE AIMS WILL ACCELERATE DEVELOPMENT OF SQ3370, A NOVEL THERAPY THAT PROMISES TO ULTIMATELY RESULT IN IMPROVED TREATMENT AND OUTCOMES FOR MILLIONS OF PATIENTS WITH SOLID TUMORS.