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John Strickler

Professor of Medicine
Medicine, Medical Oncology
Dept of Medicine, BOX_2823, Durham, NC 27710

Selected Publications


A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study.

Journal Article Future Oncol · March 2024 WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article describing an ongoing study called MOUNTAINEER. This article was published in The Lancet Oncology in 2023. The study included 117 adults with metastatic HER2-positive colorectal cancer. The resea ... Full text Link to item Cite

Racial and ethnic disparities in genomic testing among lung cancer patients: a systematic review.

Journal Article J Natl Cancer Inst · February 6, 2024 INTRODUCTION: Racial and ethnic disparities in genomic testing could exacerbate disparities in access to precision cancer therapies and survival-particularly in the context of lung cancer, where genomic testing has been recommended for the past decade. How ... Full text Link to item Cite

Targeting KRAS-Mutated Gastrointestinal Malignancies with Small-Molecule Inhibitors: A New Generation of Breakthrough Therapies.

Journal Article Drugs · January 2024 Kirsten rat sarcoma virus (KRAS) is one of the most important and frequently mutated oncogenes in cancer and the mutational prevalence is especially high in many gastrointestinal malignancies, including colorectal cancer and pancreatic ductal adenocarcinom ... Full text Link to item Cite

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial.

Journal Article Nat Med · January 2024 The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, a ... Full text Link to item Cite

Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma.

Journal Article J Gastrointest Cancer · December 22, 2023 BACKGROUND: Gastroesophageal cancer is a major cause of cancer-related mortality worldwide. Treatment of both early stage and advanced disease remains highly reliant on cytotoxic chemotherapy. About 4-24% of gastroesophageal cancers are microsatellite inst ... Full text Link to item Cite

Prevalence of KRAS G12C Mutation and Co-mutations and Associated Clinical Outcomes in Patients With Colorectal Cancer: A Systematic Literature Review.

Journal Article Oncologist · November 2, 2023 PURPOSE: A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of th ... Full text Link to item Cite

Identification of an optimal mutant allele frequency to detect activating KRAS, NRAS, and BRAF mutations in a commercial cell-free DNA next-generation sequencing assay in colorectal and pancreatic adenocarcinomas.

Journal Article J Gastrointest Oncol · October 31, 2023 BACKGROUND: Evaluation for activating mutations in KRAS, NRAS, and BRAF in colorectal cancer (CRC) and in KRAS in pancreatic ductal adenocarcinoma (PDAC) is essential for clinical care. Plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) allows c ... Full text Link to item Cite

Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes.

Journal Article Oncologist · October 3, 2023 BACKGROUND: HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this associ ... Full text Link to item Cite

Trends in Receipt of Adjuvant Chemotherapy and its Impact on Survival in Resected Biliary Tract Cancers.

Journal Article Ann Surg Oncol · August 2023 BACKGROUND: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and su ... Full text Link to item Cite

Hepatic artery infusion for unresectable colorectal cancer liver metastases: Palliation and conversion.

Journal Article Surgery · August 2023 Patients with unresectable colorectal liver metastases are commonly treated with systemic chemotherapy to convert their disease to an operable state. Unfortunately, many patients remain unresectable after first-line chemotherapy and resort to second- and t ... Full text Link to item Cite

Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study.

Journal Article J Natl Compr Canc Netw · August 2023 BACKGROUND: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there we ... Full text Link to item Cite

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.

Journal Article Cancer Immunol Immunother · July 2023 BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer ... Full text Link to item Cite

Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.

Journal Article Lancet Oncol · May 2023 BACKGROUND: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. METHODS: M ... Full text Link to item Cite

A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study.

Journal Article Future Oncol · March 2024 WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article describing an ongoing study called MOUNTAINEER. This article was published in The Lancet Oncology in 2023. The study included 117 adults with metastatic HER2-positive colorectal cancer. The resea ... Full text Link to item Cite

Racial and ethnic disparities in genomic testing among lung cancer patients: a systematic review.

Journal Article J Natl Cancer Inst · February 6, 2024 INTRODUCTION: Racial and ethnic disparities in genomic testing could exacerbate disparities in access to precision cancer therapies and survival-particularly in the context of lung cancer, where genomic testing has been recommended for the past decade. How ... Full text Link to item Cite

Targeting KRAS-Mutated Gastrointestinal Malignancies with Small-Molecule Inhibitors: A New Generation of Breakthrough Therapies.

Journal Article Drugs · January 2024 Kirsten rat sarcoma virus (KRAS) is one of the most important and frequently mutated oncogenes in cancer and the mutational prevalence is especially high in many gastrointestinal malignancies, including colorectal cancer and pancreatic ductal adenocarcinom ... Full text Link to item Cite

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial.

Journal Article Nat Med · January 2024 The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, a ... Full text Link to item Cite

Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma.

Journal Article J Gastrointest Cancer · December 22, 2023 BACKGROUND: Gastroesophageal cancer is a major cause of cancer-related mortality worldwide. Treatment of both early stage and advanced disease remains highly reliant on cytotoxic chemotherapy. About 4-24% of gastroesophageal cancers are microsatellite inst ... Full text Link to item Cite

Prevalence of KRAS G12C Mutation and Co-mutations and Associated Clinical Outcomes in Patients With Colorectal Cancer: A Systematic Literature Review.

Journal Article Oncologist · November 2, 2023 PURPOSE: A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of th ... Full text Link to item Cite

Identification of an optimal mutant allele frequency to detect activating KRAS, NRAS, and BRAF mutations in a commercial cell-free DNA next-generation sequencing assay in colorectal and pancreatic adenocarcinomas.

Journal Article J Gastrointest Oncol · October 31, 2023 BACKGROUND: Evaluation for activating mutations in KRAS, NRAS, and BRAF in colorectal cancer (CRC) and in KRAS in pancreatic ductal adenocarcinoma (PDAC) is essential for clinical care. Plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) allows c ... Full text Link to item Cite

Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes.

Journal Article Oncologist · October 3, 2023 BACKGROUND: HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this associ ... Full text Link to item Cite

Trends in Receipt of Adjuvant Chemotherapy and its Impact on Survival in Resected Biliary Tract Cancers.

Journal Article Ann Surg Oncol · August 2023 BACKGROUND: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and su ... Full text Link to item Cite

Hepatic artery infusion for unresectable colorectal cancer liver metastases: Palliation and conversion.

Journal Article Surgery · August 2023 Patients with unresectable colorectal liver metastases are commonly treated with systemic chemotherapy to convert their disease to an operable state. Unfortunately, many patients remain unresectable after first-line chemotherapy and resort to second- and t ... Full text Link to item Cite

Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study.

Journal Article J Natl Compr Canc Netw · August 2023 BACKGROUND: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there we ... Full text Link to item Cite

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.

Journal Article Cancer Immunol Immunother · July 2023 BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer ... Full text Link to item Cite

Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.

Journal Article Lancet Oncol · May 2023 BACKGROUND: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. METHODS: M ... Full text Link to item Cite

Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer.

Journal Article J Clin Oncol · February 10, 2023 PURPOSE: Overexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-dr ... Full text Link to item Cite

Treatment of Metastatic Colorectal Cancer: ASCO Guideline.

Journal Article J Clin Oncol · January 20, 2023 PURPOSE: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Fi ... Full text Link to item Cite

Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board.

Journal Article Oncologist · January 18, 2023 OBJECTIVE: The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance betwe ... Full text Open Access Link to item Cite

Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer.

Journal Article N Engl J Med · January 5, 2023 BACKGROUND: KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C-mutated pancreatic cancer are unknown. METHODS: We conducte ... Full text Link to item Cite

Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T m ... Full text Link to item Cite

Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue.

Journal Article Case Rep Oncol · 2023 "Liquid biopsy" is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal can ... Full text Link to item Cite

Hepatic Artery Infusion Pumps: A Surgical Toolkit for Intraoperative Decision-Making and Management of Hepatic Artery Infusion-Specific Complications.

Journal Article Ann Surg · December 1, 2022 BACKGROUND: Hepatic artery infusion (HAI) is a liver-directed therapy that delivers high-dose chemotherapy to the liver through the hepatic arterial system for colorectal liver metastases and intrahepatic cholangiocarcinoma. Utilization of HAI is rapidly e ... Full text Link to item Cite

Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis.

Journal Article Sci Rep · November 9, 2022 Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I ... Full text Link to item Cite

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study.

Journal Article Future Oncol · September 2022 Aim: This phase II study investigated safety and efficacy of dilpacimab or bevacizumab plus FOLFIRI in patients with previously treated metastatic colorectal cancer (mCRC). Materials & methods: Overall, 66 patients were treated (n = 34 dilpacimab + FOLFIRI ... Full text Link to item Cite

BRAF-Mutated Advanced Colorectal Cancer: A Rapidly Changing Therapeutic Landscape.

Journal Article J Clin Oncol · August 20, 2022 BRAF-mutated advanced colorectal cancer is a relatively small but critical subset of this tumor type on the basis of prognostic and predictive implications. BRAF alterations in colorectal cancer are classified into three functional categories on the basis ... Full text Link to item Cite

A narrative review of the evolving role of immunotherapy in the management of esophageal and gastric cancer.

Journal Article J Gastrointest Oncol · August 2022 BACKGROUND AND OBJECTIVE: Despite recent advances in the multidisciplinary management of esophagogastric cancer, overall prognosis remains poor. There is a need for improved treatment options, along with predictive biomarkers that improve therapeutic decis ... Full text Link to item Cite

Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer: A Review.

Journal Article JAMA Oncol · May 1, 2022 IMPORTANCE: Amplification of ERBB2 (formerly referred to as HER2) is present in nearly 3% of patients with metastatic colorectal cancer overall and 5% of patients with KRAS and NRAS wild-type tumors. Despite the availability of several ERBB2-targeted thera ... Full text Link to item Cite

A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.

Journal Article Clin Cancer Res · March 1, 2022 PURPOSE: TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) is a co-inhibitory receptor of T-cell and natural killer cell activity. Targeting TIGIT with or without PD-1/PD-L1 checkpoint inhibition ma ... Full text Link to item Cite

Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers.

Journal Article Cancer Chemother Pharmacol · March 2022 PURPOSE: Acquired resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC) remains a hurdle for effective treatment. MET amplification has been indicated as a driver of acquired resistance. Clinical activity has been demonstrated for the combin ... Full text Link to item Cite

Phase 1b/2, open-label, dose-escalation and expansion trial of tucatinib in combination with trastuzumab with and without oxaliplatin-based chemotherapy or pembrolizumab in patients with unresectable or metastatic HER2+ gastrointestinal cancers (trial in progress).

Conference Journal of Clinical Oncology · February 1, 2022 TPS376 Background: Human epidermal growth factor receptor 2 ( HER2) gene amplification or protein overexpression (HER2+) occurs in many gastrointestinal (GI) cancers; thus, there is interest in evaluating HER2-targeted therapies ... Full text Cite

REVERCEII (ACCRU-GI-1809): A randomized phase II study of regorafenib followed by anti-EGFR monoclonal antibody therapy versus the reverse sequencing for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irinotecan.

Conference Journal of Clinical Oncology · February 1, 2022 TPS213 Background: Regorafenib (R) is an oral multikinase inhibitor that blocks several protein kinases involved in angiogenesis and oncogenesis; it has a survival benefit in refractory metastatic colorectal cancer (mCRC). The cu ... Full text Cite

A phase 1b study of sotorasib, a specific and irreversible KRASG12C inhibitor, in combination with other anticancer therapies in advanced colorectal cancer (CRC) and other solid tumors (CodeBreaK 101).

Conference Journal of Clinical Oncology · February 1, 2022 TPS214 Background: Approximately 3% of patients (pts) with CRC have the oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation. Sotorasib, a small molecule that specifically and irreversibly inhibits the KRAS ... Full text Cite

Perioperative and oncologic outcomes of hepatic artery infusion pump therapy at an expanding HAI program.

Conference Journal of Clinical Oncology · February 1, 2022 120 Background: Hepatic artery infusion (HAI) is a liver directed therapy to treat unresectable or resected colorectal liver metastases (CRLM) and unresectable intrahepatic cholangiocarcinoma (ICC). Historically, HAI has only bee ... Full text Cite

MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in progress.

Conference Journal of Clinical Oncology · February 1, 2022 TPS371 Background: Tucatinib (TUC), a highly selective HER2-directed tyrosine kinase inhibitor (TKI) approved in multiple regions for HER2+ metastatic breast cancer, is being developed as a novel therapy for patients (pts) with G ... Full text Cite

Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.

Journal Article Lancet Oncol · January 2022 BACKGROUND: Sotorasib, a specific, irreversible KRASG12C protein inhibitor, has shown monotherapy clinical activity in KRASG12C-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and ... Full text Link to item Cite

Genomic and Precision Medicine: Oncology, Third Edition

Book · January 1, 2022 Genomic and Precision Medicine: Oncology, Third Edition focuses on the applications of genome discovery as research points to personalized cancer therapies. Each chapter is organized to cover the application of genomics and personalized medicine tools and ... Full text Cite

Introduction and overview of cancer precision medicine

Chapter · January 1, 2022 While cancer causes premature death in millions of persons around the globe yearly, in the last few years incredible advances have been made in our understanding of molecular drivers of cancers. Cancer treatment programs have benefited significantly from t ... Full text Cite

Preface

Book · January 1, 2022 Full text Cite

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Journal Article Clin Lung Cancer · November 2021 INTRODUCTION: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab ac ... Full text Link to item Cite

First-In-Human, First-In-Class, Phase I Trial of the Fucosylation Inhibitor SGN-2FF in Patients with Advanced Solid Tumors.

Journal Article The oncologist · November 2021 Lessons learnedInhibition of glycoprotein fucosylation, as monotherapy and in combination with immune checkpoint blockade, is a promising therapeutic strategy for treating a broad range of cancers. In this first-in-human, first-in-class, phase I s ... Full text Cite

Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non-Small Cell Lung Carcinoma.

Journal Article Clin Cancer Res · November 1, 2021 PURPOSE: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate. Here, we present safety and efficacy data from a phase I/Ib study of Teliso-V monotherapy evaluated in once every 2 weeks/once every 3 weeks schedules in patients ... Full text Link to item Cite

Safety, Efficacy, and Biomarker Results from a Phase Ib Study of the Anti-DKK1 Antibody DKN-01 in Combination with Pembrolizumab in Advanced Esophagogastric Cancers.

Journal Article Mol Cancer Ther · November 2021 Therapeutic combinations targeting innate and adaptive immunity and predictive biomarkers of response in esophagogastric cancer (EGC) are needed. We assessed safety and clinical utility of DKN-01 (a novel DKK1-neutralizing IgG4 antibody) combined with pemb ... Full text Link to item Cite

393 A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers

Conference Journal for ImmunoTherapy of Cancer · November 2021 BackgroundSBT6050 is a novel therapeutic comprising a selective small molecule toll-like receptor 8 (TLR8) agonist linked to the HER2-directed monoclonal antibody pertuzumab, allowing for combination with trastuzu ... Full text Cite

Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors.

Journal Article Mol Cancer Ther · October 2021 Dilpacimab (formerly ABT-165), a novel dual-variable domain immunoglobulin, targets both delta-like ligand 4 (DLL4) and VEGF pathways. Here, we present safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data from a phase I study ( ... Full text Link to item Cite

Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer.

Journal Article Oncology (Williston Park, N.Y.) · October 2021 Metastatic colorectal cancer (mCRC) is the second most common cause of cancer-related death worldwide. In the mid-1980s, the median overall survival (OS) for patients with mCRC ranged from 10 to 12 months from the time of initial diagnosis. In more recent ... Full text Cite

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.

Journal Article Oncologist · June 2021 LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or ... Full text Link to item Cite

Trial in progress: A phase 1b study of sotorasib, a specific and irreversible KRASG12C inhibitor, as monotherapy in non-small cell lung cancer (NSCLC) with brain metastasis and in combination with other anticancer therapies in advanced solid tumors (CodeBreaK 101).

Conference Journal of Clinical Oncology · May 20, 2021 TPS2669 Background: Kirsten rat sarcoma viral oncogene homolog ( KRAS) p.G12C mutation is an oncogenic driver mutation in several solid tumors. Sotorasib is a specific, irreversible, small molecule inhibitor of KRASG12C ... Full text Cite

Assessment of HER2 (ERBB2) amplification (HER2amp) using blood-based circulating tumor DNA (ctDNA) next generation sequencing (NGS) and correlation with tissue-based testing in metastatic colorectal cancer (mCRC).

Conference Journal of Clinical Oncology · May 20, 2021 3589 Background: HER2 amplified mCRC has emerged as a unique clinical subset, characterized by resistance to anti-EGFR therapy and response to anti-HER2 strategies. Accurate identification and quantification of HER2amp has predic ... Full text Cite

Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC).

Conference Journal of Clinical Oncology · May 20, 2021 9047 Background: Upregulation of CD73 in multiple cancers increases adenosine production, leading to local immunosuppression. Oleclumab, a human IgG1λ mAb, inhibits CD73 function and may increase antitumor immunity. Initial data ... Full text Cite

Serial circulating tumor DNA (ctDNA) monitoring in metastatic colorectal cancer (mCRC) reveals dynamic profile of actionable alterations.

Conference Journal of Clinical Oncology · May 20, 2021 3572 Background: Serial ctDNA can measure dynamic changes in disease burden over time, however utility of serial profiling to detect changes in actionable alterations remains unclear. Methods: We evaluated 501 patients with ≥3 se ... Full text Cite

Preliminary clinical and biologic results of GB1275, a first-in-class oral CD11b modulator, alone and with pembrolizumab, in advanced solid tumors (KEYNOTE A36).

Conference Journal of Clinical Oncology · May 20, 2021 2505 Background: GB1275 is a first-in-class, oral CD11b modulator that reduced myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs), repolarized M2 immunosuppressive TAMs to an M1 phenotype, resulting ... Full text Cite

Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.

Journal Article Cell Rep · May 4, 2021 While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway is associated with diminished T cell infiltration; however, activating ... Full text Open Access Link to item Cite

Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better?

Journal Article Clin Cancer Res · March 1, 2021 Immune checkpoint inhibitors, including antibodies that block programmed cell death protein-1 (PD-1) and PD-L1, have transformed the management of many cancers. However, the majority of patients have primary or acquired resistance to these immunotherapies. ... Full text Link to item Cite

Targeting MET Amplification with Crizotinib in a Case of Sinonasal Undifferentiated Carcinoma.

Journal Article Cancer Invest · March 2021 Comprehensive molecular testing of individual tumors has led to the identification of novel molecularly defined cancer therapies and treatment indications. Given low frequencies of many molecular alterations, efficacy of therapies used to target them are o ... Full text Link to item Cite

Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer.

Journal Article Annu Rev Med · January 27, 2021 Patient-specific biomarkers form the foundation of precision medicine strategies. To realize the promise of precision medicine in patients with colorectal cancer (CRC), access to cost-effective, convenient, and safe assays is critical. Improvements in diag ... Full text Link to item Cite

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

Conference Journal of Clinical Oncology · January 20, 2021 228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination ... Full text Cite

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

Conference Journal of Clinical Oncology · January 20, 2021 TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. B ... Full text Cite

MOUNTAINEER:open-label, phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress).

Conference Journal of Clinical Oncology · January 20, 2021 TPS153 Background: The clinical benefit of approved therapies in patients (pts) with metastatic colorectal cancer (mCRC) who progress on first- and second-line chemotherapy (FOLFOX and FOLFIRI) is limited. In pts with chemotherap ... Full text Cite

MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress.

Conference Journal of Clinical Oncology · January 20, 2021 TPS252 Background: Tucatinib (TUC), a highly selective HER2-directed TKI recently approved for HER2+ metastatic breast cancer (MBC), is being developed as a novel therapy for patients (pts) with metastatic colorectal cancer (mCRC ... Full text Cite

Real-world genomic and treatment landscape in advanced colorectal cancer identifies treatment differences pre- and post-ctDNA genomic profiling.

Conference Journal of Clinical Oncology · January 20, 2021 39 Background: Clinical insights gained from real-world data have led to numerous advances in oncology including new and expanded drug approvals and an understanding of real-world clinical utilization. In this precision oncology ... Full text Cite

Impact of Postoperative Chemotherapy on the Survival of Patients with High-Grade Gastroenteropancreatic Neuroendocrine Carcinoma.

Journal Article Ann Surg Oncol · January 2021 BACKGROUND: This study aimed to determine whether postoperative chemotherapy is associated with a survival benefit for patients with poorly differentiated neuroendocrine carcinoma (NEC) of the stomach, small bowel, or pancreas. METHODS: Patients were ident ... Full text Link to item Cite

Results and Clinical Utilization of Foundation Medicine Molecular Tumor Profiling in Uterine and Ovarian Cancers.

Journal Article Target Oncol · January 2021 BACKGROUND: Recent advances in next-generation sequencing have allowed for an increase in molecular tumor profiling. OBJECTIVE: We sought to assess the actionability and clinical utilization of molecular tumor profiling results obtained via Foundation Medi ... Full text Link to item Cite

A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.

Journal Article AME case reports · January 2021 Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, ... Full text Cite

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

Journal Article JCO Precis Oncol · 2021 UNLABELLED: Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most ... Full text Link to item Cite

ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal-Anal Task Forces whitepaper.

Journal Article Nat Rev Clin Oncol · December 2020 An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal-Anal Task Forces of the United States Na ... Full text Link to item Cite

Implementation of a Hepatic Artery Infusion Program: Initial Patient Selection and Perioperative Outcomes of Concurrent Hepatic Artery Infusion and Systemic Chemotherapy for Colorectal Liver Metastases.

Journal Article Ann Surg Oncol · December 2020 BACKGROUND: Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few c ... Full text Link to item Cite

KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.

Journal Article N Engl J Med · September 24, 2020 BACKGROUND: No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that se ... Full text Link to item Cite

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study.

Journal Article Lancet Oncol · June 2020 BACKGROUND: Dual blockade of PD-L1 and VEGF has enhanced anticancer immunity through multiple mechanisms and augmented antitumour activity in multiple malignancies. We aimed to assess the efficacy and safety of atezolizumab (anti-PD-L1) alone and combined ... Full text Link to item Cite

Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors.

Journal Article Mol Cancer Ther · May 2020 This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced s ... Full text Link to item Cite

Overcoming Resistance to Targeted Therapies in Gastrointestinal Cancers: Progress to Date and Progress to Come.

Journal Article Am Soc Clin Oncol Educ Book · May 2020 Targeted therapies have transformed the treatment paradigm in diseases such as non-small cell lung cancer and melanoma but have shown relatively modest clinical benefit in gastrointestinal malignancies. Anti-EGFR therapy in RAS wild-type colorectal cancer, ... Full text Link to item Cite

Genetic counseling referrals after next generation sequencing testing.

Conference JOURNAL OF CLINICAL ONCOLOGY · 2020 Cite

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

Journal Article BMC Cancer · November 1, 2019 BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (R ... Full text Link to item Cite

A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).

Journal Article Cancer Chemother Pharmacol · October 2019 PURPOSE: This study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with ... Full text Link to item Cite

A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.

Journal Article Cancer Med · September 2019 PURPOSE: Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. PATIENTS AND METHODS: Aphase 2, randomized, placebo-controlled, multice ... Full text Link to item Cite

Adjuvant Chemotherapy Improves Survival Following Resection of Locally Advanced Rectal Cancer with Pathologic Complete Response.

Conference J Gastrointest Surg · August 2019 BACKGROUND: Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective an ... Full text Link to item Cite

Abstract 1675: Analytical validation of MSI High detection with GuardantOMNI

Conference Cancer Research · July 1, 2019 AbstractBackground: Late stage therapy selection is advancing beyond the detection of classical driver alterations (SNV, Indel, CNV, Fusion) to the use of aggregate biomarkers comprising combinations of SNVs ... Full text Cite

Abstract LB-235: COLOMATE: Colorectal cancer and liquid biopsy screening protocol for molecularly assigned therapy

Conference Cancer Research · July 1, 2019 AbstractBackground: Colorectal cancer (CRC) is the second leading cause of cancer death among men and women in the United States, and additional treatment strategies are needed for patients with advanced dis ... Full text Cite

Blood-based genomic profiling of cell-free DNA (cfDNA) to identify microsatellite instability (MSI-H), tumor mutational burden (TMB) and Wnt/B-Catenin pathway alterations in patients with gastrointestinal (GI) tract cancers.

Conference Journal of Clinical Oncology · May 20, 2019 3552 Background: MSI-H cancers are responsive to immune checkpoint blockade (ICB), but nearly half of all patients experience primary or early treatment resistance. Activation of the WNT/B-Catenin pathway can lead to immune exclu ... Full text Cite

Prediction model for detecting circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).

Conference Journal of Clinical Oncology · May 20, 2019 3590 Background: While tissue-based assays have yields above 90% in solid tumors, there is less known about factors that influence the sensitivity of ctDNA for detecting mutations. Methods:We retrospectively evaluated mCRC patien ... Full text Cite

Results of the phase 1b study of ABBV-399 (telisotuzumab vedotin; teliso-v) in combination with erlotinib in patients with c-Met+ non-small cell lung cancer by EGFR mutation status.

Conference Journal of Clinical Oncology · May 20, 2019 3011 Background: Telisotuzumab vedotin (ABBV-399; teliso-v [T]) is a c-Met–targeted antibody and MMAE drug conjugate. Activity of T was shown in late-line c-Met+ non-small cell lung cancer (NSCLC) irrespective of EGFR mutation (M ... Full text Cite

Third- or Later-line Therapy for Metastatic Colorectal Cancer: Reviewing Best Practice.

Journal Article Clin Colorectal Cancer · March 2019 An increasing number of patients with metastatic colorectal cancer (mCRC) are able to receive 3 or more lines of therapy. Treatments in this setting can include regorafenib (an oral multikinase inhibitor), trifluridine/tipiracil hydrochloride (TAS-102), an ... Full text Link to item Cite

Comprehensive landscape of gene amplifications (amps) in tissue and circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).

Conference Journal of Clinical Oncology · February 1, 2019 604 Background: Amps, as oncogenic and resistance drivers, have therapeutic implications, but unlike mutations, have been sparsely described in mCRC. Functional account is piecemeal due to vague definitions, limited data on co-oc ... Full text Cite

ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.

Conference Journal of Clinical Oncology · February 1, 2019 TPS720 Background: Dual variable domain immunoglobulin ABT-165 targets human vascular endothelial growth factor (VEGF) and delta-like ligand 4 (DLL4). Combined VEGF and DLL4 blockade increased inhibition of subcutaneous xenograft ... Full text Cite

Quantifying the evolution of tumor architecture using serial circulating tumor DNA.

Conference Journal of Clinical Oncology · February 1, 2019 600 Background: There is limited data regarding changes in the genomic landscape in individual patients over time as serial tissue biopsy has risk and is of uncertain clinical benefit. The advent of circulating tumor DNA (ctDNA) ... Full text Cite

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.

Journal Article Ann Oncol · February 2019 BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a gro ... Full text Link to item Cite

First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors.

Journal Article J Clin Oncol · November 20, 2018 PURPOSE: This first-in-human study evaluated telisotuzumab vedotin (Teliso-V), formerly called ABBV-399, an antibody-drug conjugate of the anti-c-Met monoclonal antibody ABT-700 and monomethyl auristatin E. MATERIALS AND METHODS: For dose escalation, three ... Full text Link to item Cite

A within-trial cost-effectiveness analysis of panitumumab compared with bevacizumab in the first-line treatment of patients with wild-type RAS metastatic colorectal cancer in the US.

Journal Article J Med Econ · November 2018 AIMS: This analysis investigated the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) compared with bevacizumab plus mFOLFOX6 in the first-line treatment of patients with wild-type RAS metastatic colorectal canc ... Full text Link to item Cite

Abstract 5551: SGN-2FF: A small-molecule inhibitor of fucosylation modulates immune cell activity in preclinical models and demonstrates pharmacodynamic activity in early phase 1 analysis

Conference Cancer Research · July 1, 2018 AbstractSGN-2FF, an orally bioavailable small molecule inhibitor of glycoprotein fucosylation, demonstrates encouraging preclinical antitumor activity in mouse models with suggested multiple mechanisms of ac ... Full text Cite

EGFR Amplification as a Target in Gastroesophageal Adenocarcinoma: Do Anti-EGFR Therapies Deserve a Second Chance?

Journal Article Cancer Discov · June 2018 Anti-EGFR therapies have failed to improve survival for unselected patients with metastatic gastroesophageal cancer, but in a subset of patients, EGFR amplification may predict treatment benefit. Maron and colleagues report the clinical activity of an ... Full text Link to item Cite

A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours.

Conference Br J Cancer · April 2018 BACKGROUND: Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid t ... Full text Link to item Cite

Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer.

Journal Article Cancer Discov · February 2018 "Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect ge ... Full text Link to item Cite

Serial monitoring of ctDNA to highlight mutation profiles in colorectal cancer.

Conference Journal of Clinical Oncology · February 1, 2018 641 Background: Circulating tumor DNA (ctDNA) represents an ideal platform to obtain the most current genomic profile of a patient’s tumor. We aimed to investigate how stable these profiles remain during serial ctDNA assays in me ... Full text Cite

Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours.

Journal Article Br J Clin Pharmacol · January 2018 AIMS: This phase 1, open-label, crossover study sought to evaluate drug-drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P-glycoprotein. METHODS: The effect of tivantinib doses on the pharmacokinetics of the prob ... Full text Link to item Cite

Cell-Free DNA Profiling to Discover Mechanisms of Exceptional Response to Cabozantinib Plus Panitumumab in a Patient With Treatment Refractory Metastatic Colorectal Cancer.

Journal Article Front Oncol · 2018 MET amplification is rare in treatment-naïve metastatic colorectal cancer (CRC) tumors, but can emerge as a mechanism of resistance to anti-EGFR therapies. Preclinical and clinical data suggest that patients with MET amplified tumors benefit from MET-targe ... Full text Link to item Cite

Targeting BRAF in metastatic colorectal cancer: Maximizing molecular approaches.

Journal Article Cancer Treat Rev · November 2017 Oncogenic mutations in B-type Raf kinase (BRAF) occur in 7-10% of metastatic colorectal cancers (mCRC). Despite recent improvements in survival in the general population of patients with mCRC, patients with BRAF-mutant mCRC continue to have poor response t ... Full text Link to item Cite

A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).

Conference Journal of Clinical Oncology · May 20, 2017 TPS3624 Background: To improve survival for patients with mCRC, efforts are needed to identify and treat actionable genomic alterations. HER2 is amplified in approximately 5-8% of patients with KRAS and NRAS (RAS) wild-type mCRC. ... Full text Cite

Phase I study of ABBV-399, a c-Met antibody-drug conjugate (ADC), as monotherapy and in combination with erlotinib in patients (pts) with non-small cell lung cancer (NSCLC).

Conference Journal of Clinical Oncology · May 20, 2017 2509 Background: The c-Met receptor is overexpressed in ~50% of pts with NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Precli ... Full text Cite

Safety and activity of the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib in phase 1 study patients (Pts) with molecularly selected advanced cholangiocarcinoma (CCA).

Conference Journal of Clinical Oncology · May 20, 2017 4074 Background: Erdafitinib (JNJ-42756493) is a potent, oral pan-FGFR tyrosine kinase inhibitor that demonstrated encouraging preliminary clinical activity and manageable adverse events (AEs) in its first-in-human phase 1 study ... Full text Cite

Paracrine wnt-β-catenin signaling inhibition as a strategy to enhance the efficacy of anti-PD-1 antibody (Ab) therapy in a transgenic model of melanoma.

Conference Journal of Clinical Oncology · May 20, 2017 3053 Background: Activation of the Wnt-β-catenin signaling pathway is associated with poor T cell infiltration of tumors. We have previously demonstrated that paracrine Wnt5a-β-catenin signaling is a critical trigger of dendritic ... Full text Cite

Blood-based genomic profiling of circulating cell-free tumor DNA (ctDNA) in 1397 patients (pts) with colorectal cancer (CRC).

Conference Journal of Clinical Oncology · February 1, 2017 584 Background: ctDNA is shed into the bloodstream by tumor cells throughout the body, offering a non-invasive means of genomic testing, and a way to detect heterogeneous, subclonal genomic alterations present in distinct tumor l ... Full text Cite

Results of a randomized phase II trial of an anti-notch 2/3, tarextumab (OMP-59R5, TRXT, anti-Notch2/3), in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC).

Conference Journal of Clinical Oncology · February 1, 2017 279 Background: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors. Tumor regression seen in Notch3 (N3) expressing pt-derived pancreatic cancer xenografts when TRXT combined with Nab-P+Gem. Ph ... Full text Cite

Biomarker studies in a phase I trial of DKN-01 in advanced esophageal cancer.

Conference Journal of Clinical Oncology · February 1, 2017 161 Background: DKK1 is a modulator of Wnt signaling that is frequently overexpressed in tumors and such expression has been associated with worse survival. Preclinical studies have shown that DKK1 can promote tumor growth by inc ... Full text Cite

Clinical applications of liquid biopsies in gastrointestinal oncology.

Journal Article J Gastrointest Oncol · October 2016 "Liquid biopsies" are blood based assays used to detect and analyze circulating tumor products, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating microRNA (miRNA), circulating exosomes, a ... Full text Open Access Link to item Cite

Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

Journal Article J Clin Oncol · August 1, 2016 PURPOSE: To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radia ... Full text Link to item Cite

Development of a Novel c-MET-Based CTC Detection Platform.

Journal Article Mol Cancer Res · June 2016 UNLABELLED: Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a fe ... Full text Open Access Link to item Cite

X-TRAP: Phase I/II study of capecitabine (X) plus ziv-aflibercept (TRAP) in metastatic colorectal cancer (mCRC).

Conference Journal of Clinical Oncology · February 1, 2016 687 Background: Patients (pts) with chemotherapy refractory mCRC have a poor prognosis, with a median survival of approximately 6 months (mos). Ziv-aflibercept is FDA-approved in combination with FOLFIRI for the 2nd Full text Cite

Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome.

Journal Article Eur Heart J · January 21, 2016 AIMS: Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS. METHODS AN ... Full text Link to item Cite

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.

Journal Article Cancer Chemother Pharmacol · April 2015 PURPOSE: To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins. METHODS: This first-in-man study in patients with advanced cancer used an accelerated ... Full text Link to item Cite

Final results of phase Ib of anticancer stem cell antibody tarextumab (OMP-59R5, TRXT, anti-Notch 2/3) in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC).

Conference Journal of Clinical Oncology · January 20, 2015 278 Background: Tarextumab (TRXT), fully human IgG2 antibody, inhibits signaling Notch 2, 3 receptors. Tumor regression seen in Notch 3 patient-derived PC xenografts when TRXT added to Nab-P+Gem. The maximum tolerated dose (MTD) ... Full text Cite

Phase I study of ABT-700, an anti-c-Met antibody, in patients (pts) with advanced gastric or esophageal cancer (GEC).

Conference Journal of Clinical Oncology · January 20, 2015 167 Background: MET is a receptor tyrosine kinase associated with treatment resistance. MET amplification (MA) results in c-Met overexpression and activation through autodimerization, and may be an important oncogenic driver in p ... Full text Cite

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: Results of a first-in-man study

Journal Article Cancer Chemotherapy and Pharmacology · January 1, 2015 Purpose: To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins. Methods: This first-in-man study in patients with advanced cancer used an accelerated ... Full text Cite

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

Journal Article Invest New Drugs · August 2014 PURPOSE: To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. DESIGN: This was a standard "3 + 3" dose-escalation trial. All subjects received b ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article Invest New Drugs · April 2014 PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). M ... Full text Link to item Cite

Gastroesophageal heterotopia and HER2/neu overexpression in an adenocarcinoma arising from a small bowel duplication.

Journal Article Arch Pathol Lab Med · March 2014 Small bowel duplications are congenital structures commonly lined by heterotopic gastric or pancreatic mucosa. Though benign in children, small bowel duplications have the potential for malignant degeneration in adulthood. Here, we present the first report ... Full text Link to item Cite

Palliative treatment of metastatic colorectal cancer: what is the optimal approach?

Journal Article Curr Oncol Rep · 2014 Worldwide, colorectal cancer (CRC) is responsible for over 600,000 deaths annually and remains a significant public health concern. Because of therapeutic advancements over the past two decades, patients with metastatic CRC are living longer with an improv ... Full text Link to item Cite

Abstract C85: Drug interaction study of tivantinib in cancer subjects using a cocktail approach.

Journal Article Molecular Cancer Therapeutics · November 1, 2013 AbstractBackground: Tivantinib (ARQ197) is an orally administered cMET inhibitor currently under development as a cancer therapy. Nonclinical studies have indicated that tivantinib and its major metabolites ... Full text Cite

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization.

Journal Article N Engl J Med · October 4, 2012 BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, ... Full text Link to item Cite

Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors.

Journal Article Cancer Chemother Pharmacol · August 2012 PURPOSE: To define the maximum tolerated dose, clinical toxicities, and pharmacodynamics of bevacizumab, everolimus, and panobinostat (LBH-589) when administered in combination to patients with advanced solid tumor malignancies. EXPERIMENT DESIGN: Subjects ... Full text Link to item Cite

Maintenance therapy for first-line metastatic colorectal cancer: activity and sustainability.

Journal Article Oncologist · 2012 Results of a study, published in this issue of The Oncologist, comparing capecitabine and oxaliplatin plus bevacizumab with the same regimen for only six cycles followed by bevacizumab monotherapy in metastatic colorectal cancer patients are examined. ... Full text Link to item Cite

Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer.

Journal Article Oncologist · 2012 Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article J Clin Oncol · May 20, 2011 3586 Background: SRC is a non-receptor tyrosine kinase involved in normal and tumor cell signaling functions including cell proliferation, angiogenesis and survival. Dasatinib (D) is a potent inhibitor of SRC kinase activity. Preclinical data suggests the ... Link to item Cite

Homeostatic proliferation plus regulatory T-cell depletion promotes potent rejection of B16 melanoma.

Journal Article Clin Cancer Res · May 15, 2008 PURPOSE: To investigate the antitumor efficacy of T-cell anergy reversal through homeostatic proliferation and regulatory T-cell (Treg) depletion in a clinically relevant murine adoptive immunotherapy model. EXPERIMENTAL DESIGN: B16 melanoma cells were eng ... Full text Link to item Cite

Jaagsiekte Sheep Retrovirus Env Protein Stabilizes Retrovirus Vectors against Inactivation by Lung Surfactant, Centrifugation, and Freeze-Thaw Cycling

Journal Article Journal of Virology · September 15, 2001 ABSTRACTJaagsiekte sheep retrovirus (JSRV) replicates in the lungs of sheep and causes the secretion of copious lung fluid containing the virus. Adaptation of JSRV to infection and replication in the lung and its ... Full text Cite