The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

6 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • PD-L2 (Programmed Cell Death 1 Ligand 2)

PD-L1 expression

Mekinist (trametinib) • ipatasertib (RG7440)

UmbrellaMAX: A Rollover Study for Participants Previously Enrolled in a Genentech and/or F. Hoffman-La Roche Sponsored Study (clinicaltrials.gov)

P3, N=100, Recruiting, Hoffmann-La Roche | N=60 --> 100

1 month ago

Enrollment change

Avastin (bevacizumab) • Rozlytrek (entrectinib) • ipatasertib (RG7440) • divarasib (RG6330) • Itovebi (inavolisib) • tiragolumab (RG6058)

Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With PTEN/AKT Mutations, A ComboMATCH Treatment Trial (clinicaltrials.gov)

P2, N=33, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

1 month ago

Trial suspension

AKT2 (V-akt murine thymoma viral oncogene homolog 2)

AKT1 mutation

paclitaxel • ipatasertib (RG7440)

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov)

P1/2, N=316, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2027 --> May 2029 | Trial primary completion date: Nov 2027 --> May 2029

1 month ago

Trial completion date • Trial primary completion date

ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)

HER-2 positive • ER positive

Herceptin (trastuzumab) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • everolimus • Verzenio (abemaciclib) • Kisqali (ribociclib) • ipatasertib (RG7440) • Itovebi (inavolisib) • giredestrant (RG6171) • Pegasys (pegylated interferon α -2a) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) • samuraciclib (CT7001)

2ms

MYBL2 regulates the expression of CENPF in lung adenocarcinoma and promotes tumor development and metastasis through AKT pathway activation. (PubMed, Eur J Med Res)

The expression of MYBL2 and CENPF in lung adenocarcinoma increases with LUAD progression. MYBL2 regulates the expression of CENPF in LUAD, and the elevated CENPF promotes the proliferation and migration of LUAD cells. Both MYBL2 and CENPF regulate the proliferation and migration of LUAD through AKT pathway activation.

2 months ago

Journal

MYBL2 (MYB Proto-Oncogene Like 2) • CENPF (Centromere Protein F)

ipatasertib (RG7440)

2ms

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)

P1/2, N=314, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

2 months ago

Trial completion

PD-L1 (Programmed death ligand 1)

PD-L1 expression

Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • Repatha (evolocumab) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)

2ms

Addition of ipatasertib to dual anti-HER2 maintenance therapy in HER2-positive metastatic breast tumors with PIK3CA mutations: the phase 1b SOLTI-1507 IPATHER trial. (PubMed, Clin Cancer Res)

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

2 months ago

P1 data • Journal

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HER-2 positive • PIK3CA mutation

Herceptin (trastuzumab) • Perjeta (pertuzumab) • ipatasertib (RG7440)

2ms

Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)

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

2 months ago

Enrollment change • Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PD-L1 expression • PIK3CA mutation

VENTANA PD-L1 (SP142) Assay

Avastin (bevacizumab) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • letrozole • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • atirmociclib (PF-07220060) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)

3ms

Enhanced expression of CXCL1 in renal cell carcinoma facilitates tumor cell malignancy via PI3K/AKT-dependent mechanisms. (PubMed, Oncol Lett)

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.

3 months ago

Journal • IO biomarker

MSI (Microsatellite instability) • CD4 (CD4 Molecule) • BAX (BCL2-associated X protein) • CXCL1 (Chemokine (C-X-C motif) ligand 1)

ipatasertib (RG7440)

3ms

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)

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

3 months ago

Trial completion date

PD-L1 (Programmed death ligand 1)

PD-L1 expression

3ms

Computational evaluation of AKT2 mutations reveals R274H and R467W as potential drivers of protein instability and inhibitor resistance in cancer therapy. (PubMed, PLoS One)

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.

3 months ago

Journal

AKT2 (V-akt murine thymoma viral oncogene homolog 2)

Truqap (capivasertib) • ipatasertib (RG7440)

3ms

Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With PTEN/AKT Mutations, A ComboMATCH Treatment Trial (clinicaltrials.gov)

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

3 months ago

Enrollment open

AKT2 (V-akt murine thymoma viral oncogene homolog 2)

AKT1 mutation

paclitaxel • ipatasertib (RG7440)