Truqap (capivasertib)

Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL-1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset.

Notably, the oncogenic effects of GJB6 ablation could be pharmacologically reversed by the AKT inhibitor capivasertib, suggesting a potential therapeutic strategy for GJB6-deficient ESCC patients. Collectively, our findings establish GJB6 as both a critical suppressor and a clinically actionable prognostic biomarker, highlighting the potential of drug repurposing approaches for ESCC treatment.

P1, N=54, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: May 2026 --> Mar 2028

Studies on capivasertib as monotherapy or in combination with fulvestrant, paclitaxel, or olaparib were included. Capivasertib constitutes a clinically validated therapeutic approach for the inhibition of AKT signaling in breast cancer. Its efficacy is most evident when combined with endocrine therapy; however, optimization of patient selection and rational combination strategies remains necessary to overcome resistance associated with mTORC1 activation and signaling redundancy.

These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/mTNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy. Addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit. PD-L1 expression was associated with enhanced antitumor activity across all arms.

These results suggest potential utility for IHC in determining tumor PTEN status in breast cancer and raise the possibility of IHC identifying additional patients who could benefit from treatment with capivasertib and fulvestrant.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P2, N=423, Completed, University of Birmingham | Active, not recruiting --> Completed

Recently, the oral, selective AKT kinase inhibitor capivasertib has been approved for the treatment of estrogen receptor-positive/human HER2-growth factor receptor-2 advanced BC with alterations in PIK3CA/AKT1/PTEN, in combination with fulvestrant after progression on endocrine therapy. We performed a narrative review to recapitulate the available evidence about capivasertib in the management of advanced hormone receptor-positive, HER2-negative breast cancer, focusing on studies that address preclinical rationale, pharmacology, and clinically relevant problems.

This study investigates the synergistic effects of capivasertib, an Akt pathway inhibitor, in combination with B-Raf inhibitors (vemurafenib and encorafenib) in B-Raf-mutated melanoma models. Systemic toxicity analyses revealed no significant changes in body weight or serum markers of pancreatic, kidney, or liver function. These findings establish capivasertib and B-Raf inhibitor combinations as a safe and effective strategy for overcoming resistance B-Raf-mutated melanoma, providing new insights into the potential of dual pathway targeting.

Despite clinical benefits, capivasertib plus fulvestrant was not cost effective at current price from a U.S. payer's perspective. The cost of capivasertib per 4 weeks would be required to decrease by ∼80% from $28,332 to $5,598 (about $87 per 200 mg) to meet the WTP threshold of $150,000.

For patients with high FLT1 expression, a combination therapy targeting this network-screened via molecular docking and dynamics simulations-may improve prognosis. This includes FLT1 inhibitors (Sorafenib, Regorafenib, Lenvatinib), supplemented by AKT1 inhibitors (Capivasertib) and VEGFA inhibitors (Bevacizumab) to suppress FLT1-associated malignant cell populations.