Neoplasms

Blood and Lymph Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Nervous System Diseases

Heart and Blood Diseases

Musculoskeletal Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Leukemia

Breast Neoplasms

Adenocarcinoma

Pancreatic Neoplasms

Glioma

Osteosarcoma

Sarcoma

Carcinoma, Renal Cell

Neoplasm Metastasis

Lung Neoplasms

Lymphoma

Hematologic Neoplasms

Ataxia

Cerebellar Ataxia

Leukemia, T-Cell

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Telangiectasis

Bone Neoplasms

Kidney Neoplasms

Ataxia Telangiectasia

Colorectal Neoplasms

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Breast Diseases

Skin Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Hematologic Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Bone Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pancreatic Cancer

Renal Cell Carcinoma

Soft Tissue Sarcoma

Lymphosarcoma

Acute Graft Versus Host Disease

Leukemia, T-cell, Chronic

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Irinotecan

Doxorubicin

Liposomal doxorubicin

Lomustine

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Topoisomerase I Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Drugs: Gemcitabine - 21 day cycle. 9-ING-41

Drugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.

Drugs: Paclitaxel. Carboplatin. 9-ING-41.

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

9-ING-41

Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle

Gemcitabine - 21 day cycle

Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.

Doxorubicin.

Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

Carboplatin.

Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle

Nab paclitaxel.

Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.

Paclitaxel.

Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle

Gemcitabine - 28 day cycle

Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

* Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.
* Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.
* Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

9-ING-41 in Patients With Advanced Cancers

Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors

The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 4.03 will be conduced at each protocol-specified timepoint.

To determine the 1-year survival rate of patients treated on the 9-ING-41 schedule chosen from the run-in stage of the study compared to the control arm

Actuate Therapeutics Inc.

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