Vicky Rowlands
A5044158671- Advanced Breast Cancer Therapies
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Renal cell carcinoma treatment
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
AstraZeneca (United Kingdom)
2017-2021
AstraZeneca (United States)
2020
Abstract Purpose: This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives were to investigate safety, tolerability, and pharmacokinetics define recommended dosing schedule, evaluate preliminary clinical activity. Experimental Design: Patients aged ≥18 years World Health Organization (WHO) performance status 0 1. Dose escalation conducted...
Abstract Liquid biopsies offer the potential to monitor cancer response and resistance therapeutics in near real-time. However, plasma cell free DNA (cfDNA) level can be low fraction of circulating tumour (ctDNA) bearing a mutation – lower still. Detection tumour-derived mutations ctDNA is thus challenging requires highly sensitive specific assays. Droplet digital PCR (ddPCR) technique that enables exquisitely detection quantification DNA/RNA markers from very limiting clinical samples,...
Abstract Purpose: The activating mutation AKT1E17K occurs in approximately 7% of estrogen receptor–positive (ER+) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability and activity capivasertib, an oral AKT inhibitor, as monotherapy or combined with fulvestrant expansion cohorts patients AKT1E17K-mutant ER+ MBC. Patients Methods: mutation, detected by local (next-generation sequencing) central (plasma-based BEAMing) testing,...
Abstract Purpose: Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations the ligand-binding domain of gene (ESR1LBDm). ESR1 mutational mediated may be overcome by selective degraders (SERD). During first-in-human study oral SERD AZD9496, early changes circulating tumor cells (CTCs) DNA (ctDNA) were explored as potential noninvasive tools, alongside paired biopsies,...
Nearly all estrogen receptor (ER)‐positive (POS) metastatic breast cancers become refractory to endocrine (ET) and other therapies, leading lethal disease presumably due evolving genomic alterations. Timely monitoring of the molecular events associated with response/progression by serial tissue biopsies is logistically difficult. Use liquid biopsies, including circulating tumor cells (CTC) DNA (ctDNA), might provide highly informative, yet easily obtainable, evidence for better precision...
<p>Supplementary Figure 2. PFS Association With {greater than or equal to}50% Decrease from Baseline in AKT1E17K at Cycle 2 Day 1 ctDNA</p>
<p>Supplementary Figure 3. AKT1E17K Allele Frequency (AF) Distribution and Median AF for patients with available ctDNA NGS data</p>
<p>Supplementary Figure 1. Participant Flow Diagram</p>
<p>Supplementary tables</p>
<p>Supplementary methods and results Supplementary Figure 1. Study 1 (NCT01226316) design 2. Dose escalation DLTs in Part A, with MTDs of the continuous, 4/7, 2/7 schedules being 320, 480, 640 mg bid, respectively 3. Exploratory mutation analyses (ddPCR) archival tissue plasma (ctDNA) samples from a breast cancer patient who had progressive disease as best response (Cb cohort) 4. A) Tumour growth inhibition preclinical tumor xenograft models (BT474c, HGC-27, HCC1954 786.0) treated...
<p>Supplementary Figure 2. PFS Association With {greater than or equal to}50% Decrease from Baseline in AKT1E17K at Cycle 2 Day 1 ctDNA</p>
<p>Supplementary tables</p>
<p>Supplementary Figure 3. AKT1E17K Allele Frequency (AF) Distribution and Median AF for patients with available ctDNA NGS data</p>
<p>Supplementary Figure 1. Participant Flow Diagram</p>
<div>Abstract<p><b>Purpose:</b> This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives were to investigate safety, tolerability, and pharmacokinetics define recommended dosing schedule, evaluate preliminary clinical activity.</p><p><b>Experimental Design:</b> Patients aged ≥18 years World...
<div>AbstractPurpose:<p>Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations the ligand-binding domain of gene (<i>ESR1<sub>LBD</sub>m</i>). <i>ESR1</i> mutational mediated may be overcome by selective degraders (SERD). During first-in-human study oral SERD AZD9496, early changes circulating tumor cells (CTCs) DNA...
<div>AbstractPurpose:<p>The activating mutation <i>AKT1</i><sup>E17K</sup> occurs in approximately 7% of estrogen receptor–positive (ER<sup>+</sup>) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability and activity capivasertib, an oral AKT inhibitor, as monotherapy or combined with fulvestrant expansion cohorts patients <i>AKT1</i><sup>E17K</sup>-mutant...
<div>Abstract<p><b>Purpose:</b> This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives were to investigate safety, tolerability, and pharmacokinetics define recommended dosing schedule, evaluate preliminary clinical activity.</p><p><b>Experimental Design:</b> Patients aged ≥18 years World...
<div>AbstractPurpose:<p>The activating mutation <i>AKT1</i><sup>E17K</sup> occurs in approximately 7% of estrogen receptor–positive (ER<sup>+</sup>) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability and activity capivasertib, an oral AKT inhibitor, as monotherapy or combined with fulvestrant expansion cohorts patients <i>AKT1</i><sup>E17K</sup>-mutant...
<div>AbstractPurpose:<p>Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations the ligand-binding domain of gene (<i>ESR1<sub>LBD</sub>m</i>). <i>ESR1</i> mutational mediated may be overcome by selective degraders (SERD). During first-in-human study oral SERD AZD9496, early changes circulating tumor cells (CTCs) DNA...
<p>Supplementary methods and results Supplementary Figure 1. Study 1 (NCT01226316) design 2. Dose escalation DLTs in Part A, with MTDs of the continuous, 4/7, 2/7 schedules being 320, 480, 640 mg bid, respectively 3. Exploratory mutation analyses (ddPCR) archival tissue plasma (ctDNA) samples from a breast cancer patient who had progressive disease as best response (Cb cohort) 4. A) Tumour growth inhibition preclinical tumor xenograft models (BT474c, HGC-27, HCC1954 786.0) treated...