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9-ING-41 in Patients With Advanced Cancers

Active: Yes
Cancer Type: Bladder Cancer
Bone Tumor
Brain & Spinal Cord Tumor
Breast Cancer
Non-Hodgkin Lymphoma
Ovarian Cancer
Pancreatic Cancer
NCT ID: NCT03678883
Trial Phases: Phase I
Phase II
Protocol IDs: 1801 (primary)
Eligibility: 18 Years and older, Male and Female Study Type: Treatment
Study Sponsor: Actuate Therapeutics Inc.
NCI Full Details:


GSK-3ß 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-3ß
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-3ß 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-3a and GSK-3ß, with both shared and distinct substrates and
functional effects. GSK-3ß 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-3ß 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-?B) and c-Myc pathways as well on tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic
mechanisms. GSK-3ß helps maintain malignant cell survival and proliferation, particularly in
terms of mediating resistance to standard anti-cancer therapies, through the NF-?B pathway.
GSK-3ß 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-3ß inhibitor with broad spectrum
pre-clinical antitumor activity. It's modes of action include downregulation of NF-?B and
decreasing the expression NF-?B 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-?B is constitutively active in cancer cells and promotes anti-apoptotic molecule
expression. NF-?B 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.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.