Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)

IPATunity150: A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov)

P3, N=20, Terminated, Hoffmann-La Roche | Completed --> Terminated; The decision to not open the Phase III portion was based on a strategic sponsor decision and not driven by any safety concerns.

1 month ago

Trial termination • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

HER-2 negative

Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)

2ms

MyTACTIC: A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response (clinicaltrials.gov)

P2, N=252, Completed, Genentech, Inc. | Active, not recruiting --> Completed

2 months ago

Trial completion • Tumor mutational burden • Metastases

Tecentriq (atezolizumab) • Rozlytrek (entrectinib) • paclitaxel • docetaxel • Alecensa (alectinib) • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • capecitabine • Gavreto (pralsetinib) • Tukysa (tucatinib) • ipatasertib (RG7440) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) • tiragolumab (RG6058)

2ms

IPATential150: Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer (clinicaltrials.gov)

P3, N=1101, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2023 --> Apr 2024

2 months ago

Trial completion date • Metastases

PTEN (Phosphatase and tensin homolog)

abiraterone acetate • ipatasertib (RG7440) • prednisone

2ms

Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation. (PubMed, Sci Signal)

A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068...Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling.

2 months ago

Journal

MAPK8 (Mitogen-activated protein kinase 8)

ipatasertib (RG7440)

2ms

Prostate Cancer Biomarker Enrichment and Treatment Selection (clinicaltrials.gov)

P2, N=200, Active, not recruiting, Canadian Cancer Trials Group | Recruiting --> Active, not recruiting | N=600 --> 200

2 months ago

Enrollment closed • Enrollment change

carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab) • adavosertib (AZD1775) • Orpathys (savolitinib) • ipatasertib (RG7440) • Nubeqa (darolutamide) • ocifisertib (CFI-400945)

2ms

NRG-GY028: Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers (clinicaltrials.gov)

P1/2, N=96, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

2 months ago

Enrollment open • Metastases

AKT1S1 (AKT1 Substrate 1)

ipatasertib (RG7440) • megestrol

3ms

Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Treating Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)

P1/2, N=28, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2023

3 months ago

Trial completion • Trial completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)

HER-2 negative

Tecentriq (atezolizumab) • carboplatin • paclitaxel • capecitabine • ipatasertib (RG7440)

3ms

Prostate Cancer Biomarker Enrichment and Treatment Selection (clinicaltrials.gov)

P2, N=600, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

3 months ago

Trial completion date • Trial primary completion date

carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab) • adavosertib (AZD1775) • Orpathys (savolitinib) • ipatasertib (RG7440) • Nubeqa (darolutamide) • ocifisertib (CFI-400945)

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=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026

3 months ago

Enrollment change • Trial completion date • Trial primary completion date • Metastases

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) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)

3ms

AFT-50 EndoMAP: A phase Ib/II multi-cohortÂ study of targeted agents for patients with recurrent or persistent endometrial cancer (SGO 2024)

Approximately, 30% of recurrent EC pts fall into this category.Â Pairing ICI with targeted therapies carries the potential to elicit prolonged anti-tumor effects.Â Atezolizumab (Atezo) is a humanized monoclonalÂ PD-L1 inhibitor that has demonstrated monotherapy antitumor activity with an acceptable safety profile in relapsed recurrent EC...In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) â‰¥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), and Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB). The Atezo+bevacizumab (biomarker unmatched) arm is closed to enrollment...Pts will receive Atezo in addition to the targeted agent (at the study approved dosing schedule) until progression,Â unacceptable toxicity, pt or physician decision to withdraw from the study, death, or study termination.Â Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole.Â The primary endpoint for Cohort A is confirmed overall response rate (ORR)Â for each cohort, and for Cohort B is progression free survival at 6 months...As a platform study, additional arms may be added, as supported by evolving understanding of EC and molecular targets. EndoMAP is actively enrolling at 18 sites in the US with a target of 25 sites nationwide.

3 months ago

P1/2 data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

MSI-H/dMMR • HER-2 amplification • HER-2 mutation

FoundationOne® CDx

Avastin (bevacizumab) • Tecentriq (atezolizumab) • Kadcyla (ado-trastuzumab emtansine) • Talzenna (talazoparib) • letrozole • ipatasertib (RG7440) • inavolisib (GDC-0077) • tiragolumab (RG6058)

4ms

Discovery of novel Akt1 inhibitors by an ensemble-based virtual screening method, molecular dynamics simulation, and in vitro biological activity testing. (PubMed, Mol Divers)

The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

4 months ago

Preclinical • Journal

AKT1 (V-akt murine thymoma viral oncogene homolog 1)

AKT1 overexpression

ipatasertib (RG7440)

5ms

First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results. (PubMed, Clin Cancer Res)

In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.

5 months ago

Journal • PD(L)-1 Biomarker • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CCND3 (Cyclin D3)

Tecentriq (atezolizumab) • albumin-bound paclitaxel • ipatasertib (RG7440)

5ms

Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer. (PubMed, Cancers (Basel))

Inhibition of the AKT/mTOR pathway by ipatasertib effectively increased the anti-tumor activity of oleic acid in endometrial cancer cells. Oleic acid treatment (10 mg/kg, daily, oral) for four weeks significantly inhibited tumor growth by 52.1% in the LKB1p53 mice. Our findings demonstrated that oleic acid exhibited anti-tumorigenic activities, dependent on the PTEN/AKT/mTOR signaling pathway, in endometrial cancer.

5 months ago

Journal

PTEN (Phosphatase and tensin homolog)

ipatasertib (RG7440)

6ms

Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers (clinicaltrials.gov)

P1/2, N=96, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

6 months ago

Trial suspension • Metastases

AKT1S1 (AKT1 Substrate 1)

ipatasertib (RG7440) • megestrol

6ms

PATHFINDER: Ipatasertib Plus Non-Taxane Chemotherapy for Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)

P2, N=54, Completed, MedSIR | Active, not recruiting --> Completed | Phase classification: P2a --> P2

6 months ago

Trial completion • Phase classification • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)

ER expression

carboplatin • gemcitabine • capecitabine • Halaven (eribulin mesylate) • ipatasertib (RG7440)

6ms

Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers (clinicaltrials.gov)

P1/2, N=96, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

6 months ago

Phase classification • Metastases

AKT1S1 (AKT1 Substrate 1)

ipatasertib (RG7440) • megestrol

6ms

Ipat-Lung: Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy (clinicaltrials.gov)

P2, N=60, Recruiting, Jun Zhang, MD, PhD | Trial primary completion date: Aug 2023 --> Aug 2024

6 months ago

Trial primary completion date • Combination therapy • Metastases

docetaxel • ipatasertib (RG7440)

6ms

FAIM: Fulvestrant, Ipatasertib and CDK4/6 Inhibition in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression (clinicaltrials.gov)

P2, N=324, Recruiting, Royal Marsden NHS Foundation Trust | Trial completion date: Aug 2024 --> Sep 2026 | Trial primary completion date: Aug 2023 --> Sep 2026

6 months ago

Trial completion date • Trial primary completion date • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

HER-2 positive • ER positive • HER-2 negative • PIK3CA mutation • HER-2 mutation • ER positive + HER-2 negative • CDK4 mutation

Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • ipatasertib (RG7440) • Pegasys (pegylated interferon α -2a)

7ms

A Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer (mCRPC). (clinicaltrials.gov)

P1, N=6, Terminated, Hoffmann-La Roche | Completed --> Terminated; Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.

7 months ago

Trial termination • Combination therapy • Metastases

Tecentriq (atezolizumab) • docetaxel • ipatasertib (RG7440)

7ms

P3, N=20, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

7 months ago

Trial completion • Metastases

HER-2 negative

Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)

7ms

The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy (clinicaltrials.gov)

P2; Trial completion date: Aug 2024 --> Jun 2025 | Trial primary completion date: Apr 2024 --> Dec 2024

7 months ago

Trial completion date • Trial primary completion date • Tumor mutational burden

PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene)

FoundationOne® CDx • FoundationOne® Liquid CDx

Opdivo (nivolumab) • Tecentriq (atezolizumab) • erlotinib • Yervoy (ipilimumab) • Ibrance (palbociclib) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • everolimus • lapatinib • Alecensa (alectinib) • Perjeta (pertuzumab) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Talzenna (talazoparib) • Piqray (alpelisib) • Retevmo (selpercatinib) • Alunbrig (brigatinib) • Gavreto (pralsetinib) • Pemazyre (pemigatinib) • ipatasertib (RG7440) • Tepmetko (tepotinib) • itacitinib (INCB039110)

7ms

B Targeted Therapy Matched To Genomic Alterations (Brafv600E, Ntrk, Fgfr, Ros1, Pik3Ca, Pten) In Patients With Recurrent Idh Wildtype Glioblastoma: A Real-Life Cohort Analysis From Veneto Institute Of Oncology, Padua (Italy) (EANO 2023)

All patients received radiotherapy and temozolomide as first-line therapy...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)... Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.

7 months ago

Clinical • PD(L)-1 Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ROS1 fusion • FGFR1 fusion • IDH wild-type • NTRK1 mutation • PIK3CA mutation + PTEN mutation • NTRK3 mutation

FoundationOne® CDx

Mekinist (trametinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • temozolomide • Piqray (alpelisib) • Balversa (erdafitinib) • ipatasertib (RG7440)

7ms

Testing the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer (clinicaltrials.gov)

P1, N=24, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

7 months ago

Enrollment open

HRD (Homologous Recombination Deficiency)

HRD

carboplatin • paclitaxel • ipatasertib (RG7440)

8ms

MORPHEUSt: A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)

P1/2, N=138, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

8 months ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative

Avastin (bevacizumab) • Tecentriq (atezolizumab) • tamoxifen • Verzenio (abemaciclib) • fulvestrant • ipatasertib (RG7440) • exemestane • Jingzhuda (entinostat)

8ms

BOUQUET: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)

P2, N=550, Recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> May 2028

8 months ago

Trial primary completion date

ER (Estrogen receptor)

8ms

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; Active, not recruiting --> Recruiting

8 months ago

Enrollment open • Metastases

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) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)

8ms

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

P2, N=33, Recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2023 --> Dec 2023

8 months ago

Trial initiation date • Metastases

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

AKT1 mutation

paclitaxel • ipatasertib (RG7440)

8ms

The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells. (PubMed, Nat Cancer)

MDSC infiltration and tumor growth were dampened in prostate cancer treated with the MNK1/2 inhibitor eFT508 and/or the AKT inhibitor ipatasertib, either alone or in combination with a clinically available MDSC-targeting immunotherapy. This work provides a therapeutic strategy that combines translation inhibition with available immunotherapies to restore immune surveillance in prostate cancer.

8 months ago

Journal • IO biomarker

SPP1 (Secreted Phosphoprotein 1)

ipatasertib (RG7440) • tomivosertib (eFT508)

9ms

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=470, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Nov 2026 | Trial primary completion date: Apr 2024 --> Aug 2025

9 months ago

Trial completion date • Trial primary completion date • Metastases

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)

9ms

Ipatasertib exhibits anti‑tumorigenic effects and enhances sensitivity to paclitaxel in endometrial cancer in vitro and in vivo. (PubMed, Int J Oncol)

The combination of IPAT and PTX resulted in increased expression of phosphorylated‑H2AX and KIF14, markers of DNA damage and microtubule dysfunction respectively, as compared with IPAT alone, PTX alone or placebo‑treated mice. The results of the present study provide a biological rationale to evaluate IPAT and the combination of IPAT and PTX in future clinical trials for endometrial cancer.

9 months ago

Preclinical • Journal

CASP3 (Caspase 3)

paclitaxel • ipatasertib (RG7440)

9ms

Interim analysis (IA) of the giredestrant (G) + ipatasertib (IPAT) arm in MORPHEUS Breast Cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with oestrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC) (ESMO 2023)

Table: 395P Conclusions Encouraging activity was seen with G + IPAT in pts with disease progression on 1–2 lines of ET (including a CDK4/6i), especially in pts with AKT signalling alterations. G + IPAT was well tolerated, with no unexpected safety signals.

9 months ago

Clinical • P1/2 data • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)

ER positive • HER-2 negative • ER mutation • ESR1 mutation

ipatasertib (RG7440) • giredestrant (GDC-9545)

9ms

Ipatasertib and atezolizumab in cancers with increased PI3K-AKT pathway activity: First results from the CRAFT trial (ESMO 2023)

Conclusions Ipatasertib and atezolizumab were ineffective in this patient population with PI3K-AKT-altered tumors. More stringent molecular selection criteria and an addition trial arm were implemented (arm 5).

9 months ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)

BRAF V600E • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • BRAF V600 • PTEN deletion • ALK rearrangement • BRAF V600K • AKT1 E17K • AKT1 mutation • ALK rearrangement + PIK3CA mutation

Tecentriq (atezolizumab) • ipatasertib (RG7440)

9ms

Target therapy matched to genomic alterations in patients with recurrent IDH wildtype glioblastoma: A real-life cohort analysis from Veneto Institute of Oncology, Padua (Italy) (ESMO 2023)

All pts received radiotherapy and temozolomide as first-line...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), vebreltinib (2 pts), capmatinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)...We had a dramatic response to a MET inhibitor. Deeper explorations are needed in targeting FGFR e ROS1.

9 months ago

Clinical • PD(L)-1 Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)

BRAF V600E • PIK3CA mutation • BRAF V600 • MET amplification • FGFR1 amplification • ROS1 fusion • FGFR1 fusion • IDH wild-type • PIK3CA mutation + PTEN mutation • MET fusion • NTRK fusion

10ms

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis. (PubMed, Front Oncol)

The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays...AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.

10 months ago

Preclinical • Journal

AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PBX1 (PBX Homeobox 1)

ipatasertib (RG7440)

10ms

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

P2, N=33, Recruiting, National Cancer Institute (NCI) | Initiation date: Mar 2023 --> Sep 2023

10 months ago

Trial initiation date • Metastases

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

AKT1 mutation

paclitaxel • ipatasertib (RG7440)

10ms

NCI-2021-13902: Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov)

P2, N=52, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

10 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

PD-L1 (Programmed death ligand 1)

Keytruda (pembrolizumab) • ipatasertib (RG7440)

10ms

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)

P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting

10 months ago

Enrollment open

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation

Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)

11ms

A phase Ib, open-label study evaluating the safety and efficacy of ipatasertib plus rucaparib in patients with metastatic castration-resistant prostate cancer. (PubMed, Clin Cancer Res)

Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC.

11 months ago

Journal • PARP Biomarker • Metastases

Rubraca (rucaparib) • ipatasertib (RG7440)