A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors

To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.

Start Date09 Sep 2021

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with IACS-6274

100 Translational Medicine associated with IACS-6274

100 Patents (Medical) associated with IACS-6274

Literatures (Medical) associated with IACS-6274

Exploration of Targeted Anti-tumor Therapy

Aspirin and the metabolic hallmark of cancer: novel therapeutic opportunities for colorectal cancer

Review

Author: Legge, Danny N. ; Hoskin, Ashley J. ; Vincent, Emma E. ; Williams, Ann C. ; Collard, Tracey J. ; Holt, Amy K.

Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has a recognized role in cancer prevention as well as evidence to support its use as an adjuvant for cancer treatment. Importantly there has been an increasing number of studies contributing to the mechanistic understanding of aspirins’ anti-tumour effects and these studies continue to inform the potential clinical use of aspirin for both the prevention and treatment of cancer. This review focuses on the emerging role of aspirin as a regulator of metabolic reprogramming, an essential “hallmark of cancer” required to support the increased demand for biosynthetic intermediates needed for sustained proliferation. Cancer cells frequently undergo metabolic rewiring driven by oncogenic pathways such as hypoxia-inducible factor (HIF), wingless-related integration site (Wnt), mammalian target of rapamycin (mTOR), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB), which supports the increased proliferative rate as tumours develop and progress. Reviewed here, cellular metabolic reprogramming has been identified as a key mechanism of action of aspirin and include the regulation of key metabolic drivers, the regulation of enzymes involved in glycolysis and glutaminolysis, and altered nutrient utilisation upon aspirin exposure. Importantly, as aspirin treatment exposes metabolic vulnerabilities in tumour cells, there is an opportunity for the use of aspirin in combination with specific metabolic inhibitors in particular, glutaminase (GLS) inhibitors currently in clinical trials such as telaglenastat (CB-839) and IACS-6274 for the treatment of colorectal and potentially other cancers. The increasing evidence that aspirin impacts metabolism in cancer cells suggests that aspirin could provide a simple, relatively safe, and cost-effective way to target this important hallmark of cancer. Excitingly, this review highlights a potential new role for aspirin in improving the efficacy of a new generation of metabolic inhibitors currently undergoing clinical investigation.

100 Deals associated with IACS-6274

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Endometrial Carcinoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Advanced Head and Neck Squamous Cell Carcinoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Clear Cell Adenocarcinoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
high grade serous adenocarcinoma of ovary	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Melanoma, Cutaneous Malignant	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Ovarian clear cell adenocarcinoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Refractory Endometrial Adenocarcinoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Refractory Melanoma	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Uterine Corpus Cancer	Phase 1	US	The University of Texas MD Anderson Cancer Center	09 Sep 2021
Advanced Malignant Solid Neoplasm	Phase 1	US	The University of Texas MD Anderson Cancer Center	28 May 2021

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