Lacey Padrón
A5009517654- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Neuroendocrine Tumor Research Advances
- Radiopharmaceutical Chemistry and Applications
Parker Institute for Cancer Immunotherapy
2022-2024
Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating efficacy nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) gemcitabine/nab-paclitaxel (chemotherapy) in patients first-line metastatic PDAC ( NCT03214250 ). In 105 analyzed efficacy, primary endpoint 1-year overall survival (OS) was met...
Abstract While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA and have not been examined. Here we investigate KRAS (ctKRAS) associations overall progression-free (OS/PFS) first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) patients receiving chemoimmunotherapy (“PRINCE”, NCT03214250), an independent cohort standard care (SOC) chemotherapy. For PRINCE, higher baseline plasma...
Abstract Targeting the right patient population with any given therapeutic agent largely remains an unsolved problem, and successes in pre-clinical models often do not translate into positive outcomes for patients. Recent advances multi-omics spatial profiling have highlighted diversity of tumor microenvironment compositions architectures across Our deepened understanding human disease also further demonstrates that handful used a large proportion studies seldom recapitulate biology are...
Abstract Background: Understanding cellular behavior within the context of tumor-immune microenvironment is essential to developing next-generation cancer therapies and advancing precision medicine. The inherent challenges this problem reflect complexity human biology - patient tissue heterogeneity, a multitude interacting signaling pathways, dynamic short- long-range interactions between tumor immune system, intrinsic limitations measurement techniques. Machine Learning foundation models...
Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these carry the risk immune-related adverse events (irAEs), which can diminish overall benefit ICI treatment. While associations between irAE development and survival been increasingly documented, there is a need for further understanding connections large prospective real-world cohorts. The Resistance Drivers Immuno-Oncology Patients Interrogated by Harmonized Molecular Datasets...
Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response ICI. Patients grouped based on tumoral levels: those <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) ≥15% (CD8-high) monotherapy. 79 (72 CD8-low 7 CD8-high) treated. The disease...
4137 Background: Metastatic pancreatic adenocarcinoma (mPDAC) is largely refractory to treatment, including immunotherapy. However, recent developments in chemoimmunotherapy combinations show promise. Herein, we report results from the first 2 cohorts of REVOLUTION, an ongoing, adaptive platform study designed assess safety and antitumor activity novel patients (pts) with untreated mPDAC. Methods: REVOLUTION (NCT04787991) open-label, non-randomized, exploratory trial. Pts were assigned by...
<h3>Background</h3> Tertiary Lymphoid Structures (TLS) are aggregates of immune cells that form at sites chronic inflammation. Presence tumor-associated TLS has recently been shown to associate with checkpoint inhibitor response independent known biomarkers. This makes induction a promising mechanism for novel immunotherapy target discovery. However, the gold standard detection method by pathologists is both time and labor intensive, limiting biology research scale. Recent advances in AI...
<h3>Background</h3> Although immune checkpoint inhibitors (ICI) are efficacious in some patients with cancer, many do not benefit. Identifying pre- and on-treatment biomarkers correlating clinical outcomes is essential for better treatment strategies. High recruitment of CD8+ T cells into the tumor associated improved following ICI therapy. We report orthogonal biomarker results from AMADEUS study, an all-comer solid tumors trial, which were treated nivolumab (NIVO) or without ipilimumab...
<h3>Background</h3> Checkpoint immunotherapies (CPI) have resulted in long lasting responses subsets of cancer patients. Despite this, come with the risk immune-related adverse events (irAEs) which can limit overall benefit CPI. Associations response, such as correlation between development irAE and better survival (OS), are well characterized clinical trials but less understood standard care settings wide varieties patient profiles. Thus, real-world evidence cohorts integral to bridging gap...
4010 Background: Preclinical and small clinical studies of chemoimmunotherapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) point to a yet unrealized potential clinically significant immune activation. In our phase II study the CD40 agonist antibody sotigalimab (sotiga) and/or nivolumab (nivo) with gemcitabine nab-paclitaxel (chemo), we observed promising improvements in overall survival (OS) 105 patients newly diagnosed mPDAC (NCT03214250); primary endpoint 1-year OS rate was...
<h3>Background</h3> Immune checkpoint therapy has not provided meaningful clinical benefit in patients with metastatic castration resistant prostate cancer (mCRPC). Biomarker-rich trials offer the opportunity to identify molecular targets of response and resistance potentially inform patient selection novel combinations future that improve anti-tumor responses mCRPC. <h3>Methods</h3> Two cohorts biomarker-rich PORTER platform trial tested a backbone combination CDX-301 [FLT3L] nivolumab....
<h3>Background</h3> Immune checkpoint therapy has failed to demonstrate a survival benefit for patients with metastatic castration resistant prostate cancer (mCRPC). New immunotherapy combination strategies are required improve clinical outcomes in heavily-pretreated mCRPC patients. <h3>Methods</h3> This open-label exploratory platform trial tested the safety and activity of combinations mCRPC. Three cohorts were enrolled A) bempegaldesleukin/nivolumab, B) stereotactic body radiation...
<h3>Background</h3> Metastatic pancreatic adenocarcinoma (mPDAC) remains notoriously treatment-refractory, particularly to immunotherapy; however, recent promise has been demonstrated with chemoimmunotherapy combinations.<sup>1,2</sup> REVOLUTION is an adaptive platform trial, designed further these advancements by assessing the safety and antitumor activity of parallel, novel combinations in patients untreated mPDAC. Coupled deep immune biomarker profiling, this approach will enable rapid...