ipatasertib (RG7440)

These results support ipatasertib plus HP as a safe and promising maintenance strategy for HER2-positive breast tumors harboring PIK3CAmut.

P1/2, N=792, Recruiting, Hoffmann-La Roche | N=580 --> 792 | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: May 2028 --> Sep 2030

Finally, the AKT-specific inhibitor GDC-0068 was shown to reverse the promoting effects of CXCL1 on the malignant behaviors of RCC cells. Taken together, the findings of the present study have shown that CXCL1 exhibits high expression patterns in RCC tissues and may serve diverse functions in facilitating various aspects of RCC advancement.

P1/2, N=314, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2026 --> Nov 2025

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.

P2, N=33, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting

This study indicated a DDI between ipatasertib and palbociclib, leading to increased ipatasertib exposure. The combination regimen of ipatasertib 300 mg with palbociclib and fulvestrant had a notable and manageable safety profile, that is generally consistent with the known risks of each individual study drugs in patients with HR + HER2-breast cancer.

Sapanisertib plus fulvestrant provided the greatest PFS benefit (HR 0.34, 95% CI 0.14-0.82) but had a high discontinuation rate (>15%). Among the approved therapies, ribociclib plus ET (HR 0.57, 95% CI 0.39-0.84), capivasertib plus fulvestrant (HR 0.62, 95% CI 0.51-0.75), and elacestrant (HR 0.70, 95% CI 0.55-0.89) demonstrated superior efficacy...Ipatasertib and alpelisib showed the greatest benefits in patients with PI3K/PTEN/AKT alterations. Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan and sacituzumab govitecan, outperformed standard chemotherapy, albeit with higher toxicity...Grant Assignment Decree No. 1369 adopted on 01.09.2023 by the Italian Ministry of University and Research (MUR).

P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=77, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Dec 2024 --> Jul 2026

P2, N=33, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

Vertical inhibition of the RAS/MEK/ERK pathway by targeting SHP2 or SOS1 and the downstream kinases MEK (trametinib) or ERK (temuterkib) was highly effective. Inhibition of upstream tyrosine receptor kinases with nintedanib in combination with batoprotafib or BI-3406 was also effective, and in combination with sotorasib, demonstrated synergy in spheroids harboring KRAS G12C. Dual inhibition of the RAS/MEK/ERK and PI3K/AKT/mTOR pathways by batoprotafib or sotorasib with either the mTORC1/2 inhibitor sapanisertib or the AKT inhibitor ipatasertib demonstrated combination activity, primarily in spheroids harboring KRAS G12C. The BCL-2 inhibitor venetoclax in combination with sotorasib, batoprotafib or BI-3406 resulted in additive and synergistic cytotoxicity. Lastly, concurrent inhibition of the KRAS pathway with sotorasib and batoprotafib demonstrated combination activity in spheroids containing KRAS G12C.