Truqap (capivasertib) / Otsuka, AstraZeneca - LARVOL DELTA

Analysis of Two Oncological Drugs Futibatinib and Capivasertib via Ion-Pairing With Eosin Y as a Spectrofluorimetric and Spectrophotometric Probe. (PubMed, Luminescence) - "In the concentration range of 1.0-10.0 and 2.0-10.0 μg mL-1, Beer's law was followed. The four approaches were applied to the analysis of dosage forms with a high percent recovery successfully, and they were assessed in compliance with ICH guidelines."

Journal

CAPItrue: Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients (clinicaltrials.gov) - P3 | N=560 | Recruiting | Sponsor: AstraZeneca

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Enhancing targeted therapy by combining PI3K and AKT inhibitors with or without cisplatin or vincristine in medulloblastoma cell lines in vitro. (PubMed, Biomed Pharmacother) - "This study provides pre-clinical evidence that AKT inhibitors combined with PI3K inhibitors, cisplatin, or vincristine exhibit additive/synergistic anti-MB activity, and lower doses could be used. The latter also applied to one MB line grown as spheroids, further supporting their future potential use."

Journal • Preclinical • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • FGFR

Ba/F3 AKT engineering cell lines, a powerful platform for novel drug discovery (EORTC-NCI-AACR 2024) - "The failures of AKT inhibitors LY2780301 and Bayer's BAY1125976 demonstrate that there are significant challenges and complexities in developing AKT pathway inhibitors. Currently, the most advanced AKT inhibitor in the world is capivasertib from AstraZeneca , capivasertib is primarily used in HR+ breast cancer and triple-negative breast cancer.Our team has generated 23 Ba/F3-AKT engineered cell lines, which are useful models for in vitro and in vivo drug discovery, including nearly all clinically significant mutations, such as the common AKT1/2-E17K mutations and the rare L52R, Q79K, and D323H mutations.The Ba/F3-AKT engineered cell line can be used to develop and evaluate next-generation AKT inhibitors, as well as to explore newly acquired AKT resistance mutations."

Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT2 • PIK3CA • PTEN

Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models (EORTC-NCI-AACR 2024) - "Capivasertib, a pan-AKT inhibitor, was recently approved in combination with fulvestrant for patients with hormone receptor positive locally advanced or metastatic breast cancer whose tumors harbor at least one PIK3CA/AKT1/PTEN-mutation. The combination of palazestrant, a complete estrogen receptor antagonist, and capivasertib, an AKT inhibitor, demonstrated synergy in preclinical ER+/HER2- breast cancer models. These data indicate that combining palazestrant and capivasertib is a promising therapeutic strategy to overcome acquired resistance."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • mTOR • PIK3CA • PTEN

Response to precision-guided treatments in patient-derived models of metastatic breast cancer (EORTC-NCI-AACR 2024) - "In ER+ models, response to FDA-approved targeted therapies was found in AKT1 and PIK3CA mutated models, treated by capivasertib and alpelisib combined with endocrine therapies, respectively...Three PDXs with cross-resistance to different standard of care treatments and mutations of the HRAS or BRAF genes or NF1 deletion, showed strong response to the MEK inhibitor trametinib, approved for BRAF-mutated melanoma and lung cancers. Our results demonstrate anti-tumor activity of different treatments not approved for BC, including a MEK inhibitor in PDXs with alterations of genes of the MAPK signaling pathway and a dual PI3K/mTOR inhibitor in TNBC models with alterations of genes in the PI3K/mTOR/AKT signaling pathway. PDX models can enhance the efficacy of precision medicine for MBC cancer patients."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • BRAF • BRCA1 • BRCA2 • ER • FGFR2 • HER-2 • HRAS • MAP3K1 • NF1 • PALB2 • PIK3CA • PTEN

Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial. (PubMed, Breast Cancer) - "Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen."

Journal • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

CAPItello-280: Study of Capivasertib + Docetaxel vs Placebo + Docetaxel as Treatment for Metastatic Castration Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P3 | N=1017 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

An Uncommon Case of Metastatic Breast Cancer to the Esophagus Causing Pseudoachalasia (ACG 2024) - "Case Description/ A A 65-year-old female with recurrent ER/PR+ stage II (T2N0) breast cancer on anastrozole and palbociclib presented with dysphagia to solids and liquids along with nausea and vomiting...The patient subsequently received palliative esophageal radiation therapy along with initiation of capivasertib and fulvestrant...Figure: EUS notable for circumferential esophageal wall thickening to 7mm. Enlarged lymph node at 25 cm from incisors (red arrow) measured at 18.6 x 6.6mm status post fine needle biopsy"

Clinical • Metastases • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Rare Diseases • Solid Tumor • GATA3 • GCDFP-15 • Mammaglobin

SS01 : Navigating current and emerging therapies for breast cancer (KSMO 2024) - "The second lecture will feature a direct account from the developer on the journey of developing the targeted drug, Capivasertib. Finally, the third lecture will delve deeply into strategies for overcoming drug resistance in breast cancer."

Breast Cancer • Oncology • Solid Tumor

Capivasertib in combination with fulvestrant in locally advanced or metastatic RH+ HER2- breast cancer with PIK3CA, AKT1 or PTEN alteration, after first-line hormonal therapy (PubMed, Bull Cancer) - No abstract available

Combination therapy • Journal • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

Discovery and development of capivasertib: A journey in targeted cancer therapy with an enabling role for biomarkers in the pharmacological audit trail (KSMO 2024) - No abstract available

Biomarker • Oncology

Capivasertib. (PubMed, Hosp Pharm) - "Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433."

Journal • Oncology

Capivasertib Plus Fulvestrant vs. Fulvestrant in Primary High-risk Lobular Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: German Breast Group

New P2 trial • Breast Cancer • Oncology • Solid Tumor

Real-world analysis on molecular targeted therapy recommendations and attainment rates in cancer gene panel testing for metastatic breast cancer (ESMO 2024) - "Luminal patients with PIK3CA-AKT1-PTEN alteration(s), a candidate for the AKT inhibitor capivasertib, were detected in 51% of cases (426/840)...Pembrolizumab was the most common (30 cases), followed by mTOR inhibitor (17 cases), and anti-HER2 therapy for non-HER2 subtype (10 cases)... This study clarified the real-world situation of cancer gene panel testing for mBC in Japan. Many targeted therapies are recommended, and it is important to appropriately utilize them. In addition, with the advent of new molecular targeting agents, the role of cancer gene panel testing in mBC will become increasingly important."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • PIK3CA • PTEN

Potent combination benefit of the AKT inhibitor capivasertib and the BCL-2 inhibitor venetoclax in diffuse large B cell lymphoma. (PubMed, Leukemia) - "The addition of the rituximab further deepened the durability of capivasertib and venetoclax responses in a RCHOP refractory DLBCL in vivo models. These findings provide preclinical evidence for the rational treatment combination of AKT and BCL-2 inhibitors using capivasertib and venetoclax respectively alongside anti-CD20 antibody supplementation for treatment of patients with DLBCL."

IO biomarker • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PIK3CA

CaptAin: Effect of Capivasertib on ctDNA in ER Positive Breast Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Imperial College London

Circulating tumor DNA • New P2 trial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Miniaturized protein profiling permits targeted signaling pathway analysis in individual circulating tumor cells to improve personalized treatment. (PubMed, J Transl Med) - "The ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research."

Circulating tumor cells • Journal • Tumor cell • Breast Cancer • Oncology • Solid Tumor • AKT1 • CTCs

A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas (clinicaltrials.gov) - P2 | N=124 | Recruiting | Sponsor: Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 ➔ Jan 2028 | Trial primary completion date: Oct 2024 ➔ Jan 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor • AKT1 • CCND1 • CCND2 • CCND3 • CCNE1 • CDK4 • CDK6 • CDKN2A • NF2 • PIK3CA • PTCH1 • PTEN • SMO

A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer. (PubMed, Future Oncol) - P3 | "The CAPItello-291 study is still ongoing, and more results are expected to be released in the future. Results from the CAPItello-291 study showed that capivasertib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival in participants with HR-positive/ HER2-negative advanced breast cancer whose cancer had grown or spread despite hormone therapy (with/without a CDK4/6 inhibitor).Clinical Trial Registration: NCT04305496 (CAPItello-291) (ClinicalTrials.gov)."

Journal • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

Concordance of PI3K-AKT pathway alterations between tumor and ctDNA in metastatic breast cancer (ESMO 2024) - "Considering the recent approval of capivasertib for HR+/HER2- metastatic breast cancer (MBC) harboring PI3K-AKT pathway alts based on tissue NGS, we assessed the concordance of tissue and ctDNA NGS for PIK3CA, AKT1, PTEN as well as ESR1. We identified 367 HR+/HER2- MBC pts treated at MSK with tissue NGS by MSK-IMPACT within 60 days of ctDNA NGS by either Guardant360 or MSK-ACCESS, without intervening therapy... Tissue-ctDNA concordance for the detection of any oncogenic alteration was high for PIK3CA, AKT1, moderate for ESR1, and low for PTEN. More alts were detected in ctDNA for ESR1 and in tissue for PTEN, reflecting acquired ESR1 alts after estrogen deprivation and the current lack of ctDNA assay PTEN copy number loss detection. Additional correlative analyses (e.g."

Circulating tumor DNA • Discordant • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

Elacestrant combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC): Preliminary data from ELEVATE, a phase Ib/II, open-label, umbrella study (ESMO 2024) - P1/2 | "To address other resistance mechanisms, ELEVATE (NCT05563220) evaluates elacestrant in combination with everolimus, alpelisib, capivasertib, palbociclib, ribociclib, or abemaciclib. Eligible pts have ER+, HER2− mBC. Elacestrant has the potential to become the ET backbone with targeted therapies, enabling all-oral combinations. Phase 2 for elacestrant + abemaciclib and elacestrant + everolimus are currently enrolling."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • mTOR

Exploring the benefit of combining paclitaxel with capivasertib treatment in PI3K/AKT/PTEN-altered and non-altered TNBC preclinical models (ESMO 2024) - P2, P3 | "Pre-clinical investigations indicate that paclitaxel can activate PI3K/AKT signaling in TNBC cells and that combining capivasertib with paclitaxel treatment inhibits pathway activation resulting in pathway inhibition with decreased cell proliferation and increased cell death. This effect is apparent in cells that are both PIK3CA, AKT1 or PTEN altered and in non-altered cells."

Preclinical • Oncology • Triple Negative Breast Cancer • EIF4EBP1 • PIK3CA • PTEN

Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer (mTNBC): The CAPItello-290 phase III trial (ESMO 2024) - P3 | "First-line C+P for mTNBC did not meet the predefined threshold for improving OS vs Pbo+P in either the overall population or in pts with PIK3CA/AKT1/PTEN-altered tumours. PFS numerically favoured C+P vs Pbo+P. The safety profile of C+P was broadly consistent with the known profiles of C and P."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • PIK3CA • PTEN

Potent combination benefit of the AKT inhibitor capivasertib and the BCL-2 inhibitor venetoclax in diffuse large B cell lymphoma (Leukemia, Nature) - "Capivasertib and venetoclax rapidly induced caspase and PARP cleavage in GCB-DLBCL PTEN wildtype cell lines and those harbouring PTEN mutations or reduced PTEN protein, driving prolonged tumour growth inhibition in DLBCL cell line and patient derived xenograft lymphoma models. The addition of the rituximab further deepened the durability of capivasertib and venetoclax responses in a RCHOP refractory DLBCL in vivo models."

Preclinical • Diffuse Large B Cell Lymphoma