Truqap (capivasertib)

P1/2, N=149, Active, not recruiting, Velindre NHS Trust | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2023 --> Dec 2025

P1, N=35, Not yet recruiting, AstraZeneca

The interleukin (IL)-33/thymic stromal lymphopoietin (TSLP)/IL-7-induced growth of group 2 innate lymphoid cells (ILC2) in vitro was resistant to dexamethasone (DEX), but suppressed by everolimus, an mTOR inhibitor, in a concentration-dependent manner...The combination of the pan-class I phosphatidylinositide-3 kinase inhibitor, buparlisib and the pan-Akt inhibitor, capivasertib also attenuated the resistance of IL-33/TSLP/IL-7-exposed ILC2s to DEX...This study demonstrates that activation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (mTOR) pathway induces steroid resistance in group 2 innate lymphoid cells. Targeting mTOR with everolimus restores steroid sensitivity, highlighting mTOR inhibition as a promising pharmacotherapy for steroid-resistant asthma.

P=N/A, N=130, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

We performed a pharmacovigilance disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) to evaluate stomatitis reports for alpelisib, capivasertib, everolimus, and palbociclib... These results support the use of the SAMT as an efficient screening tool. Furthermore, these findings underscore the need for optimized stomatitis detection and continued monitoring, particularly for PI3K and mTOR inhibitors, in both clinical trials and postmarketing surveillance.

Co-administering fibroblast BJ-hTERT cell supernatants with BYL719, JNJ-42756493, and PD-0332991 had an inhibitory effect on their effects on viability and confluence in some cell lines. This was never the case with cisplatin, and very rarely the case with docetaxel or AZD-5363.

P3, N=818, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2024 --> Jun 2026

Molecular docking revealed that R274H, in kinase domain, disrupts key hydrogen bonds with THR292 and GLU279, leading to more flexible binding pocket and significantly reduced binding affinity for Capivasertib and Ipatasertib. These findings suggest that these mutations may contribute to inhibitor resistance by weakening inhibitor interactions and destabilizing the protein-inhibitor complex. This study underscores the importance of genetic screening in optimizing cancer treatment and highlights the need for mutation-specific therapeutic strategies targeting AKT2.

Importantly, combined treatment with the FDA-approved AKT inhibitor capivasertib and the Src inhibitor dasatinib synergistically induced apoptosis and suppressed the tumor cell growth in various PTEN-deficient cell lines as well as in three-dimensional cultures of endometrial cancer patient-derived xenograft models. Specifically, Src-mediated upregulation of EphA2 in PTEN-deficient cells highlights a therapeutic vulnerability that can be exploited by combined AKT and Src inhibition. This approach addresses the resistance associated with AKT inhibition alone and enhances therapeutic efficacy in PTEN-deficient cancers, supporting its potential application in targeted combination therapies.

Capivasertib plus abiraterone improves rPFS versus placebo plus abiraterone in PTEN-deficient mHSPC, on a background of ADT, with a 7.5-month improvement in median rPFS. AE profile was consistent with that of the individual agents. Patients with PTEN-deficient mHSPC benefit from dual blockade of the PI3K/AKT and AR pathways with capivasertib plus abiraterone.

This case underscores the importance of real-time glucose monitoring and individualized glycemic management during capivasertib therapy, particularly in patients with metabolic risk factors. Early detection and tailored intervention may help prevent severe hyperglycemic complications and facilitate the safe continuation of treatment.

Genetic manipulation of PLAC8 through overexpression and knockdown unequivocally established its prometastatic function in CRC, with no significant effects on proliferation, oxaliplatin resistance, or colony formation. Pharmacological modulation of AKT signaling using specific activators (SC79) and inhibitors (Capivasertib) confirmed that PLAC8 drives EMT through AKT pathway activation, resulting in increased expression of EMT-related proteins, such as N-cadherin and Snail, thereby enhancing cell migration and invasion...CCL28-mediated promotion of PLAC8 via the JAK/STAT3 signaling pathway, led to EMT in colorectal cancer cells, which played a key role in the transition from inflammation to cancer. PLAC8 served as an independent risk factor for colorectal cancer prognosis.